Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process.

PubMed

Alanazi, Ibrahim O; Ebrahimie, Esmaeil

2016-07-01

Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

Shifts in rotifer life history in response to stable isotope enrichment: testing theories of isotope effects on organismal growth

PubMed Central

2017-01-01

In ecology, stable isotope labelling is commonly used for tracing material transfer in trophic interactions, nutrient budgets and biogeochemical processes. The main assumption in this approach is that the enrichment with a heavy isotope has no effect on the organism growth and metabolism. This assumption is, however, challenged by theoretical considerations and experimental studies on kinetic isotope effects in vivo. Here, I demonstrate profound changes in life histories of the rotifer Brachionus plicatilis fed 15N-enriched algae (0.4–5.0 at%); i.e. at the enrichment levels commonly used in ecological studies. These findings support theoretically predicted effects of heavy isotope enrichment on growth, metabolism and ageing in biological systems and underline the importance of accounting for such effects when using stable isotope labelling in experimental studies. PMID:28405367

GENIUS: web server to predict local gene networks and key genes for biological functions.

PubMed

Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A; Cabello, Juan M; Soto, Alvaro; Gutiérrez, Rodrigo A

2017-03-01

GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . genius.psbl@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

BiNChE: a web tool and library for chemical enrichment analysis based on the ChEBI ontology.

PubMed

Moreno, Pablo; Beisken, Stephan; Harsha, Bhavana; Muthukrishnan, Venkatesh; Tudose, Ilinca; Dekker, Adriano; Dornfeldt, Stefanie; Taruttis, Franziska; Grosse, Ivo; Hastings, Janna; Neumann, Steffen; Steinbeck, Christoph

2015-02-21

Ontology-based enrichment analysis aids in the interpretation and understanding of large-scale biological data. Ontologies are hierarchies of biologically relevant groupings. Using ontology annotations, which link ontology classes to biological entities, enrichment analysis methods assess whether there is a significant over or under representation of entities for ontology classes. While many tools exist that run enrichment analysis for protein sets annotated with the Gene Ontology, there are only a few that can be used for small molecules enrichment analysis. We describe BiNChE, an enrichment analysis tool for small molecules based on the ChEBI Ontology. BiNChE displays an interactive graph that can be exported as a high-resolution image or in network formats. The tool provides plain, weighted and fragment analysis based on either the ChEBI Role Ontology or the ChEBI Structural Ontology. BiNChE aids in the exploration of large sets of small molecules produced within Metabolomics or other Systems Biology research contexts. The open-source tool provides easy and highly interactive web access to enrichment analysis with the ChEBI ontology tool and is additionally available as a standalone library.

Comparative qualitative phosphoproteomics analysis identifies shared phosphorylation motifs and associated biological processes in evolutionary divergent plants.

PubMed

Al-Momani, Shireen; Qi, Da; Ren, Zhe; Jones, Andrew R

2018-06-15

Phosphorylation is one of the most prevalent post-translational modifications and plays a key role in regulating cellular processes. We carried out a bioinformatics analysis of pre-existing phosphoproteomics data, to profile two model species representing the largest subclasses in flowering plants the dicot Arabidopsis thaliana and the monocot Oryza sativa, to understand the extent to which phosphorylation signaling and function is conserved across evolutionary divergent plants. We identified 6537 phosphopeptides from 3189 phosphoproteins in Arabidopsis and 2307 phosphopeptides from 1613 phosphoproteins in rice. We identified phosphorylation motifs, finding nineteen pS motifs and two pT motifs shared in rice and Arabidopsis. The majority of shared motif-containing proteins were mapped to the same biological processes with similar patterns of fold enrichment, indicating high functional conservation. We also identified shared patterns of crosstalk between phosphoserines with enrichment for motifs pSXpS, pSXXpS and pSXXXpS, where X is any amino acid. Lastly, our results identified several pairs of motifs that are significantly enriched to co-occur in Arabidopsis proteins, indicating cross-talk between different sites, but this was not observed in rice. Our results demonstrate that there are evolutionary conserved mechanisms of phosphorylation-mediated signaling in plants, via analysis of high-throughput phosphorylation proteomics data from key monocot and dicot species: rice and Arabidposis thaliana. The results also suggest that there is increased crosstalk between phosphorylation sites in A. thaliana compared with rice. The results are important for our general understanding of cell signaling in plants, and the ability to use A. thaliana as a general model for plant biology. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Whole transcriptome analysis of the fasting and fed Burmese python heart: insights into extreme physiological cardiac adaptation.

PubMed

Wall, Christopher E; Cozza, Steven; Riquelme, Cecilia A; McCombie, W Richard; Heimiller, Joseph K; Marr, Thomas G; Leinwand, Leslie A

2011-01-01

The infrequently feeding Burmese python (Python molurus) experiences significant and rapid postprandial cardiac hypertrophy followed by regression as digestion is completed. To begin to explore the molecular mechanisms of this response, we have sequenced and assembled the fasted and postfed Burmese python heart transcriptomes with Illumina technology using the chicken (Gallus gallus) genome as a reference. In addition, we have used RNA-seq analysis to identify differences in the expression of biological processes and signaling pathways between fasted, 1 day postfed (DPF), and 3 DPF hearts. Out of a combined transcriptome of ∼2,800 mRNAs, 464 genes were differentially expressed. Genes showing differential expression at 1 DPF compared with fasted were enriched for biological processes involved in metabolism and energetics, while genes showing differential expression at 3 DPF compared with fasted were enriched for processes involved in biogenesis, structural remodeling, and organization. Moreover, we present evidence for the activation of physiological and not pathological signaling pathways in this rapid, novel model of cardiac growth in pythons. Together, our data provide the first comprehensive gene expression profile for a reptile heart.

Structural Analysis of N- and O-glycans Using ZIC-HILIC/Dialysis Coupled to NMR Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Yi; Feng, Ju; Deng, Shuang

2014-11-19

Protein glycosylation, an important and complex post-translational modification (PTM), is involved in various biological processes including the receptor-ligand and cell-cell interaction, and plays a crucial role in many biological functions. However, little is known about the glycan structures of important biological complex samples, and the conventional glycan enrichment strategy (i.e., size-exclusion column [SEC] separation,) prior to nuclear magnetic resonance (NMR) detection is time-consuming and tedious. In this study, we employed SEC, Zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC), and ZIC-HILIC coupled with dialysis strategies to enrich the glycopeptides from the pronase E digests of RNase B, followed by NMR analysis ofmore » the glycoconjugate. Our results suggest that the ZIC-HILIC enrichment coupled with dialysis is the most efficient, which was thus applied to the analysis of biological complex sample, the pronase E digest of the secreted proteins from the fungi Aspergillus niger. The NMR spectra revealed that the secreted proteins from A. niger contain both N-linked glycans with a high-mannose core and O-linked glycans bearing mannose and glucose with 1->3 and 1->6 linkages. In all, our study provides compelling evidence that ZIC-HILIC separation coupled to dialysis is superior to the commonly used SEC separation to prepare glycopeptides for the downstream NMR analysis, which could greatly facilitate the future NMR-based glycoproteomics research.« less

NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

PubMed

Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

2017-09-21

High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

Selective enrichment of metal-binding proteins based on magnetic core/shell microspheres functionalized with metal cations.

PubMed

Fang, Caiyun; Zhang, Lei; Zhang, Xiaoqin; Lu, Haojie

2015-06-21

Metal binding proteins play many important roles in a broad range of biological processes. Characterization of metal binding proteins is important for understanding their structure and biological functions, thus leading to a clear understanding of metal associated diseases. The present study is the first to investigate the effectiveness of magnetic microspheres functionalized with metal cations (Ca(2+), Cu(2+), Zn(2+) and Fe(3+)) as the absorbent matrix in IMAC technology to enrich metal containing/binding proteins. The putative metal binding proteins in rat liver were then globally characterized by using this strategy which is very easy to handle and can capture a number of metal binding proteins effectively. In total, 185 putative metal binding proteins were identified from rat liver including some known less abundant and membrane-bound metal binding proteins such as Plcg1, Acsl5, etc. The identified proteins are involved in many important processes including binding, catalytic activity, translation elongation factor activity, electron carrier activity, and so on.

The Molecular Signatures Database (MSigDB) hallmark gene set collection.

PubMed

Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga; Ghandi, Mahmoud; Mesirov, Jill P; Tamayo, Pablo

2015-12-23

The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

Editor's Highlight: Application of Gene Set Enrichment Analysis for Identification of Chemically Induced, Biologically Relevant Transcriptomic Networks and Potential Utilization in Human Health Risk Assessment.

PubMed

Dean, Jeffry L; Zhao, Q Jay; Lambert, Jason C; Hawkins, Belinda S; Thomas, Russell S; Wesselkamper, Scott C

2017-05-01

The rate of new chemical development in commerce combined with a paucity of toxicity data for legacy chemicals presents a unique challenge for human health risk assessment. There is a clear need to develop new technologies and incorporate novel data streams to more efficiently inform derivation of toxicity values. One avenue of exploitation lies in the field of transcriptomics and the application of gene expression analysis to characterize biological responses to chemical exposures. In this context, gene set enrichment analysis (GSEA) was employed to evaluate tissue-specific, dose-response gene expression data generated following exposure to multiple chemicals for various durations. Patterns of transcriptional enrichment were evident across time and with increasing dose, and coordinated enrichment plausibly linked to the etiology of the biological responses was observed. GSEA was able to capture both transient and sustained transcriptional enrichment events facilitating differentiation between adaptive versus longer term molecular responses. When combined with benchmark dose (BMD) modeling of gene expression data from key drivers of biological enrichment, GSEA facilitated characterization of dose ranges required for enrichment of biologically relevant molecular signaling pathways, and promoted comparison of the activation dose ranges required for individual pathways. Median transcriptional BMD values were calculated for the most sensitive enriched pathway as well as the overall median BMD value for key gene members of significantly enriched pathways, and both were observed to be good estimates of the most sensitive apical endpoint BMD value. Together, these efforts support the application of GSEA to qualitative and quantitative human health risk assessment. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

PubMed

Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

2017-03-01

People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Analysis of disease-associated objects at the Rat Genome Database

PubMed Central

Wang, Shur-Jen; Laulederkind, Stanley J. F.; Hayman, G. T.; Smith, Jennifer R.; Petri, Victoria; Lowry, Timothy F.; Nigam, Rajni; Dwinell, Melinda R.; Worthey, Elizabeth A.; Munzenmaier, Diane H.; Shimoyama, Mary; Jacob, Howard J.

2013-01-01

The Rat Genome Database (RGD) is the premier resource for genetic, genomic and phenotype data for the laboratory rat, Rattus norvegicus. In addition to organizing biological data from rats, the RGD team focuses on manual curation of gene–disease associations for rat, human and mouse. In this work, we have analyzed disease-associated strains, quantitative trait loci (QTL) and genes from rats. These disease objects form the basis for seven disease portals. Among disease portals, the cardiovascular disease and obesity/metabolic syndrome portals have the highest number of rat strains and QTL. These two portals share 398 rat QTL, and these shared QTL are highly concentrated on rat chromosomes 1 and 2. For disease-associated genes, we performed gene ontology (GO) enrichment analysis across portals using RatMine enrichment widgets. Fifteen GO terms, five from each GO aspect, were selected to profile enrichment patterns of each portal. Of the selected biological process (BP) terms, ‘regulation of programmed cell death’ was the top enriched term across all disease portals except in the obesity/metabolic syndrome portal where ‘lipid metabolic process’ was the most enriched term. ‘Cytosol’ and ‘nucleus’ were common cellular component (CC) annotations for disease genes, but only the cancer portal genes were highly enriched with ‘nucleus’ annotations. Similar enrichment patterns were observed in a parallel analysis using the DAVID functional annotation tool. The relationship between the preselected 15 GO terms and disease terms was examined reciprocally by retrieving rat genes annotated with these preselected terms. The individual GO term–annotated gene list showed enrichment in physiologically related diseases. For example, the ‘regulation of blood pressure’ genes were enriched with cardiovascular disease annotations, and the ‘lipid metabolic process’ genes with obesity annotations. Furthermore, we were able to enhance enrichment of neurological diseases by combining ‘G-protein coupled receptor binding’ annotated genes with ‘protein kinase binding’ annotated genes. Database URL: http://rgd.mcw.edu PMID:23794737

GOMA: functional enrichment analysis tool based on GO modules

PubMed Central

Huang, Qiang; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun

2013-01-01

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results. PMID:23237213

A NOVEL PROCESS FOR BIOLOGICAL NITROGEN REMOVAL FROM DAIRY WASTEWATER IN CONSTRUCTED WETLANDS

EPA Science Inventory

SUNY-ESF has a multidisciplinary P3 Team, although it is mainly composed of undergraduate students in forest engineering and graduate students in environmental and resources engineering. The Team has successfully enriched anammox bacteria in two vertical flow baffled biofilter...

Towards Complex Abiotic Systems for Chemical and Biological Sensing

DTIC Science & Technology

2009-11-01

such as phage display, cell surface display, and Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Other processes necessary to...Directed evolution by in vitro compartmentalization. Nat Methods 2006, 3, 561-570. l7Chelliserrykattil, J.; Ellington, A.D. Evolution of a T7 RNA

Separation and enrichment of trace ractopamine in biological samples by uniformly-sized molecularly imprinted polymers

PubMed Central

Li, Ya; Fu, Qiang; Liu, Meng; Jiao, Yuan-Yuan; Du, Wei; Yu, Chong; Liu, Jing; Chang, Chun; Lu, Jian

2012-01-01

In order to prepare a high capacity packing material for solid-phase extraction with specific recognition ability of trace ractopamine in biological samples, uniformly-sized, molecularly imprinted polymers (MIPs) were prepared by a multi-step swelling and polymerization method using methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, and toluene as a porogen respectively. Scanning electron microscope and specific surface area were employed to identify the characteristics of MIPs. Ultraviolet spectroscopy, Fourier transform infrared spectroscopy, Scatchard analysis and kinetic study were performed to interpret the specific recognition ability and the binding process of MIPs. The results showed that, compared with other reports, MIPs synthetized in this study showed high adsorption capacity besides specific recognition ability. The adsorption capacity of MIPs was 0.063 mmol/g at 1 mmol/L ractopamine concentration with the distribution coefficient 1.70. The resulting MIPs could be used as solid-phase extraction materials for separation and enrichment of trace ractopamine in biological samples. PMID:29403774

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis.

PubMed

Ferrari, Raffaele; Forabosco, Paola; Vandrovcova, Jana; Botía, Juan A; Guelfi, Sebastian; Warren, Jason D; Momeni, Parastoo; Weale, Michael E; Ryten, Mina; Hardy, John

2016-02-24

In frontotemporal dementia (FTD) there is a critical lack in the understanding of biological and molecular mechanisms involved in disease pathogenesis. The heterogeneous genetic features associated with FTD suggest that multiple disease-mechanisms are likely to contribute to the development of this neurodegenerative condition. We here present a systems biology approach with the scope of i) shedding light on the biological processes potentially implicated in the pathogenesis of FTD and ii) identifying novel potential risk factors for FTD. We performed a gene co-expression network analysis of microarray expression data from 101 individuals without neurodegenerative diseases to explore regional-specific co-expression patterns in the frontal and temporal cortices for 12 genes (MAPT, GRN, CHMP2B, CTSC, HLA-DRA, TMEM106B, C9orf72, VCP, UBQLN2, OPTN, TARDBP and FUS) associated with FTD and we then carried out gene set enrichment and pathway analyses, and investigated known protein-protein interactors (PPIs) of FTD-genes products. Gene co-expression networks revealed that several FTD-genes (such as MAPT and GRN, CTSC and HLA-DRA, TMEM106B, and C9orf72, VCP, UBQLN2 and OPTN) were clustering in modules of relevance in the frontal and temporal cortices. Functional annotation and pathway analyses of such modules indicated enrichment for: i) DNA metabolism, i.e. transcription regulation, DNA protection and chromatin remodelling (MAPT and GRN modules); ii) immune and lysosomal processes (CTSC and HLA-DRA modules), and; iii) protein meta/catabolism (C9orf72, VCP, UBQLN2 and OPTN, and TMEM106B modules). PPI analysis supported the results of the functional annotation and pathway analyses. This work further characterizes known FTD-genes and elaborates on their biological relevance to disease: not only do we indicate likely impacted regional-specific biological processes driven by FTD-genes containing modules, but also do we suggest novel potential risk factors among the FTD-genes interactors as targets for further mechanistic characterization in hypothesis driven cell biology work.

Synthesis of hydrazide-functionalized hydrophilic polymer hybrid graphene oxide for highly efficient N-glycopeptide enrichment and identification by mass spectrometry.

PubMed

Bai, Haihong; Pan, Yiting; Guo, Cong; Zhao, Xinyuan; Shen, Bingquan; Wang, Xinghe; Liu, Zeyuan; Cheng, Yuanguo; Qin, Weijie; Qian, Xiaohong

2017-08-15

Protein N-glycosylation is one of the most important post-translational modifications, participating in many key biological and pathological processes. Large-scale and precise identification of N-glycosylated proteins and peptides is especially beneficial for understanding their biological functions and for discovery of new clinical biomarkers and therapeutic drug targets. However, protein N-glycosylation is microheterogeneous and low abundant in living organisms, therefore specific enrichment of N-glycosylated proteins/peptides before mass spectrometry analysis is a prerequisite. In this work, we developed a new type of polymer hybrid graphene oxide (GO) by in situ growth of hydrazide-functionalized hydrophilic polymer chains on the GO surface (GO-PAAH) for selective N-glycopeptide enrichment and identification by mass spectrometry. The densely attached and low steric hindrance hydrazide groups as well as the highly hydrophilic nature of GO-PAAH facilitate N-glycopeptide enrichment by the combination of hydrazide capturing and HILIC interaction. Taking advantage of the unique features of GO-PAAH, all of the three N-glycopeptides of bovine fetuin were successfully enriched and identified with significantly enhanced signal intensities from a digest mixture of bovine fetuin and bovine serum albumin at a mass ratio of 1:100, demonstrating the excellent enrichment selectivity of GO-PAAH. Furthermore, a total of 507 N-glycosylation sites and 480 N-glycopeptides in 232 N-glycoproteins were enriched and identified from 10μL of human serum by three replicates using this novel enrichment material, which is nearly two times higher than the commercial hydrazide resin based method (280 N-glycosylation sites, 261 N-glycopeptides and 144 N-glycoproteins in three experiments). Among the identified, 95 N-glycosylation sites were not reported in the Uniprot database, and 106 N-glycoproteins were disease related in the Nextprot database, indicating the potential of this new enrichment material in global mapping of protein N-glycosylation. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of neoblast- and regeneration-specific miRNAs in the planarian Schmidtea mediterranea

PubMed Central

Sasidharan, Vidyanand; Lu, Yi-Chien; Bansal, Dhiru; Dasari, Pranavi; Poduval, Deepak; Seshasayee, Aswin; Resch, Alissa M.; Graveley, Brenton R.; Palakodeti, Dasaradhi

2013-01-01

In recent years, the planarian Schmidtea mediterranea has emerged as a tractable model system to study stem cell biology and regeneration. MicroRNAs are small RNA species that control gene expression by modulating translational repression and mRNA stability and have been implicated in the regulation of various cellular processes. Though recent studies have identified several miRNAs in S. mediterranea, their expression in neoblast subpopulations and during regeneration has not been examined. Here, we identify several miRNAs whose expression is enriched in different neoblast subpopulations and in regenerating tissue at different time points in S. mediterranea. Some of these miRNAs were enriched within 3 h post-amputation and may, therefore, play a role in wound healing and/or neoblast migration. Our results also revealed miRNAs, such as sme-miR-2d-3p and the sme-miR-124 family, whose expression is enriched in the cephalic ganglia, are also expressed in the brain primordium during CNS regeneration. These results provide new insight into the potential biological functions of miRNAs in neoblasts and regeneration in planarians. PMID:23974438

Enrichment and separation techniques for large-scale proteomics analysis of the protein post-translational modifications.

PubMed

Huang, Junfeng; Wang, Fangjun; Ye, Mingliang; Zou, Hanfa

2014-11-06

Comprehensive analysis of the post-translational modifications (PTMs) on proteins at proteome level is crucial to elucidate the regulatory mechanisms of various biological processes. In the past decades, thanks to the development of specific PTM enrichment techniques and efficient multidimensional liquid chromatography (LC) separation strategy, the identification of protein PTMs have made tremendous progress. A huge number of modification sites for some major protein PTMs have been identified by proteomics analysis. In this review, we first introduced the recent progresses of PTM enrichment methods for the analysis of several major PTMs including phosphorylation, glycosylation, ubiquitination, acetylation, methylation, and oxidation/reduction status. We then briefly summarized the challenges for PTM enrichment. Finally, we introduced the fractionation and separation techniques for efficient separation of PTM peptides in large-scale PTM analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Mineralogical and Biogeochemical Characteristics of Rhodolith from Wu Island, Jeju-do, Korea

NASA Astrophysics Data System (ADS)

Roh, Y.; Kang, S.; Roh, E. H.

2012-12-01

This study focused on investigation of mineralogical and biogeochemical characteristics of the rhodoliths and examination of the rhodolith origin whether they were formed by chemical or biological processes. Rhodoliths are free-living forms of calcareous, coralline red algae formed under specific environmental conditions, but their formation processes are still controversial. The rhodoliths and sea water were sampled at Seogwang-ri coast in the western part of Wu Island, Jeju-do, Korea. The chemical compositions and pHs of sea water were measured by ICP-AES and pH meter. Microorganisms enriched from rhodoliths were aerobically cultured at room temperature in D-1 media containing various concentrations (0, 30, 100 mM) of Ca and Mg-acetate, and the microorganisms were analyzed by 16S rRNA gene DGGE analysis to confirm microbial diversity. Mineralogical characteristics of the rhodoliths and precipitates formed by the enriched microorganisms were determined by XRF, XRD, and SEM-EDS analyses. The sea water had a range of pH 6 to 7, and consisted of approximately 400 mg/L of Ca and 1200 mg/L of Mg which are low to form carbonate minerals by chemical process in natural environments. XRF and XRD analyses showed the rhodoliths mainly consisted of 46% CaO and 5 % MgO and mineralogy is Mg-rich calcite. A 16S rRNA sequence analysis showed the enriched microorganisms contained a carbonate forming microorganism, Proteus mirabilis. The enriched microorganisms precipitated carbonate minerals using D-1 media containing Ca- and Mg-acetate (30, 100 mM) and mineralogy of the precipitated carbonate mineral was Mg-rich calcite, whereas the microorganisms did not form carbonate minerals without Ca- and Mg-acetate in D-1 media. SEM-EDS analyses showed that the Mg-rich calcite formed by the microorganisms had a rhombohedron shape. And the Mg-rich calcite consisted of Ca, Si and Mg with extracellular polymeric substance (EPS). These results indicate that the rhodoliths at Seogwang-ri coast could be formed biologically and the microorganisms induce precipitation of Mg-rich calcite on the cell walls and EPS via the accumulation of Ca and/or Mg ions on the cells. The study of the natural analogues, rhodolith beach, complements laboratory experiments and possibly provides opportunity to constrain the mechanisms for CO2-bearing phases to form via biological processes.

Molecular profiles to biology and pathways: a systems biology approach.

PubMed

Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

2016-06-16

Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

Circulating Tumor Cells: Moving Biological Insights into Detection

PubMed Central

Chen, Lichan; Bode, Ann M; Dong, Zigang

2017-01-01

Circulating tumor cells (CTCs) have shown promising potential as liquid biopsies that facilitate early detection, prognosis, therapeutic target selection and monitoring treatment response. CTCs in most cancer patients are low in abundance and heterogeneous in morphological and phenotypic profiles, which complicate their enrichment and subsequent characterization. Several methodologies for CTC enrichment and characterization have been developed over the past few years. However, integrating recent advances in CTC biology into these methodologies and the selection of appropriate enrichment and characterization methods for specific applications are needed to improve the reliability of CTC biopsies. In this review, we summarize recent advances in the studies of CTC biology, including the mechanisms of their generation and their potential forms of existence in blood, as well as the current CTC enrichment technologies. We then critically examine the selection of methods for appropriately enriching CTCs for further investigation of their clinical applications. PMID:28819450

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism

PubMed Central

Eagleson, Kathie L.; Xie, Zhihui; Levitt, Pat

2016-01-01

People with autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy - the influence of one gene on distinct phenotypes - raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multi-functional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain, and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with ASD, reduces transcription and disrupts socially-relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways, and has a complex protein interactome that is enriched in ASD and other NDD candidates. The interactome is co-regulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, impacting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. PMID:27837921

Proteolytic Digestion and TiO2 Phosphopeptide Enrichment Microreactor for Fast MS Identification of Proteins.

PubMed

Deng, Jingren; Lazar, Iulia M

2016-04-01

The characterization of phosphorylation state(s) of a protein is best accomplished by using isolated or enriched phosphoprotein samples or their corresponding phosphopeptides. The process is typically time-consuming as, often, a combination of analytical approaches must be used. To facilitate throughput in the study of phosphoproteins, a microreactor that enables a novel strategy for performing fast proteolytic digestion and selective phosphopeptide enrichment was developed. The microreactor was fabricated using 100 μm i.d. fused-silica capillaries packed with 1-2 mm beds of C18 and/or TiO2 particles. Proteolytic digestion-only, phosphopeptide enrichment-only, and sequential proteolytic digestion/phosphopeptide enrichment microreactors were developed and tested with standard protein mixtures. The protein samples were adsorbed on the C18 particles, quickly digested with a proteolytic enzyme infused over the adsorbed proteins, and further eluted onto the TiO2 microreactor for enrichment in phosphopeptides. A number of parameters were optimized to speed up the digestion and enrichments processes, including microreactor dimensions, sample concentrations, digestion time, flow rates, buffer compositions, and pH. The effective time for the steps of proteolytic digestion and enrichment was less than 5 min. For simple samples, such as standard protein mixtures, this approach provided equivalent or better results than conventional bench-top methods, in terms of both enzymatic digestion and selectivity. Analysis times and reagent costs were reduced ~10- to 15-fold. Preliminary analysis of cell extracts and recombinant proteins indicated the feasibility of integration of these microreactors in more advanced workflows amenable for handling real-world biological samples. Graphical Abstract ᅟ.

Proteolytic Digestion and TiO2 Phosphopeptide Enrichment Microreactor for Fast MS Identification of Proteins

NASA Astrophysics Data System (ADS)

Deng, Jingren; Lazar, Iulia M.

2016-04-01

The characterization of phosphorylation state(s) of a protein is best accomplished by using isolated or enriched phosphoprotein samples or their corresponding phosphopeptides. The process is typically time-consuming as, often, a combination of analytical approaches must be used. To facilitate throughput in the study of phosphoproteins, a microreactor that enables a novel strategy for performing fast proteolytic digestion and selective phosphopeptide enrichment was developed. The microreactor was fabricated using 100 μm i.d. fused-silica capillaries packed with 1-2 mm beds of C18 and/or TiO2 particles. Proteolytic digestion-only, phosphopeptide enrichment-only, and sequential proteolytic digestion/phosphopeptide enrichment microreactors were developed and tested with standard protein mixtures. The protein samples were adsorbed on the C18 particles, quickly digested with a proteolytic enzyme infused over the adsorbed proteins, and further eluted onto the TiO2 microreactor for enrichment in phosphopeptides. A number of parameters were optimized to speed up the digestion and enrichments processes, including microreactor dimensions, sample concentrations, digestion time, flow rates, buffer compositions, and pH. The effective time for the steps of proteolytic digestion and enrichment was less than 5 min. For simple samples, such as standard protein mixtures, this approach provided equivalent or better results than conventional bench-top methods, in terms of both enzymatic digestion and selectivity. Analysis times and reagent costs were reduced ~10- to 15-fold. Preliminary analysis of cell extracts and recombinant proteins indicated the feasibility of integration of these microreactors in more advanced workflows amenable for handling real-world biological samples.

Dynamic sporulation gene co-expression networks for Bacillus subtilis 168 and the food-borne isolate Bacillus amyloliquefaciens: a transcriptomic model

PubMed Central

Omony, Jimmy; de Jong, Anne; Krawczyk, Antonina O.; Eijlander, Robyn T.; Kuipers, Oscar P.

2018-01-01

Sporulation is a survival strategy, adapted by bacterial cells in response to harsh environmental adversities. The adaptation potential differs between strains and the variations may arise from differences in gene regulation. Gene networks are a valuable way of studying such regulation processes and establishing associations between genes. We reconstructed and compared sporulation gene co-expression networks (GCNs) of the model laboratory strain Bacillus subtilis 168 and the food-borne industrial isolate Bacillus amyloliquefaciens. Transcriptome data obtained from samples of six stages during the sporulation process were used for network inference. Subsequently, a gene set enrichment analysis was performed to compare the reconstructed GCNs of B. subtilis 168 and B. amyloliquefaciens with respect to biological functions, which showed the enriched modules with coherent functional groups associated with sporulation. On basis of the GCNs and time-evolution of differentially expressed genes, we could identify novel candidate genes strongly associated with sporulation in B. subtilis 168 and B. amyloliquefaciens. The GCNs offer a framework for exploring transcription factors, their targets, and co-expressed genes during sporulation. Furthermore, the methodology described here can conveniently be applied to other species or biological processes. PMID:29424683

Dynamic sporulation gene co-expression networks for Bacillus subtilis 168 and the food-borne isolate Bacillus amyloliquefaciens: a transcriptomic model.

PubMed

Omony, Jimmy; de Jong, Anne; Krawczyk, Antonina O; Eijlander, Robyn T; Kuipers, Oscar P

2018-02-09

Sporulation is a survival strategy, adapted by bacterial cells in response to harsh environmental adversities. The adaptation potential differs between strains and the variations may arise from differences in gene regulation. Gene networks are a valuable way of studying such regulation processes and establishing associations between genes. We reconstructed and compared sporulation gene co-expression networks (GCNs) of the model laboratory strain Bacillus subtilis 168 and the food-borne industrial isolate Bacillus amyloliquefaciens. Transcriptome data obtained from samples of six stages during the sporulation process were used for network inference. Subsequently, a gene set enrichment analysis was performed to compare the reconstructed GCNs of B. subtilis 168 and B. amyloliquefaciens with respect to biological functions, which showed the enriched modules with coherent functional groups associated with sporulation. On basis of the GCNs and time-evolution of differentially expressed genes, we could identify novel candidate genes strongly associated with sporulation in B. subtilis 168 and B. amyloliquefaciens. The GCNs offer a framework for exploring transcription factors, their targets, and co-expressed genes during sporulation. Furthermore, the methodology described here can conveniently be applied to other species or biological processes.

PHYSICAL AND BIOLOGICAL CONTROLS ON DISSOLVED OXYGEN DYNAMICS IN A NORTHEASTERN GULF OF MEXICO ESTUARY

EPA Science Inventory

Nutrient over-enrichment is one of the most often cited causes of 305b impairment in coastal waters. Excessive nutrients affect designated uses of the nation's aquatic resources, and pose risks to human health and the environment. The process of developing nutrient criteria for e...

Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer.

PubMed

Li, Yongsheng; Chen, Juan; Zhang, Jinwen; Wang, Zishan; Shao, Tingting; Jiang, Chunjie; Xu, Juan; Li, Xia

2015-09-22

Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes. Moreover, the development and progression of cancer often involves the combined actions of several lncRNAs. Here we propose a multi-step method for constructing lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of functional modules having three features: common coexpressed genes of lncRNA pairs, enrichment in the same functional category and close proximity within protein interaction networks. Applied to three cancers, we constructed cancer-specific LFSNs and found that they exhibit a scale free and modular architecture. In addition, cancer-associated lncRNAs tend to be hubs and are enriched within modules. Although there is little synergistic pairing of lncRNAs across cancers, lncRNA pairs involved in the same cancer hallmarks by regulating same or different biological processes. Finally, we identify prognostic biomarkers within cancer lncRNA expression datasets using modules derived from LFSNs. In summary, this proof-of-principle study indicates synergistic lncRNA pairs can be identified through integrative analysis of genome-wide expression data sets and functional information.

Identification of differentially expressed genes in Monochamus alternatus digested with azadirachtin.

PubMed

Lin, Tong; Liu, Qisi; Chen, Jingxiang

2016-09-15

The pine sawyer beetle Monochamus alternatus Hope, a major forest insect pest, is the primary vector of the destructive forest pest pine wood nematode, Bursaphelenchus xylophilus. Azadirachtin, an active compound of neem, is biologically interesting because it represents a group of important, successful botanical pesticides. We provide insight into the molecular effects of azadirachtin on M. alternatus at the transcriptional level to provide clues about possible molecular-level targets and to establish a link between azadirachtin and insect global responses. We found that 920 and 9894 unique genes were significantly up- and down-regulated, respectively. We obtained expression patterns of the differentially expressed genes (DEGs), identifying 4247, 3488 and 7613 sequences that involved cellular components, molecular functions and biological processes, respectively, and showed that the DEGs were distributed among 50 Gene Ontology categories. The Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were enriched in 50 pathways. Detailed gene profile knowledge of the interaction of azadirachtin with M. alternatus should facilitate the development of more effective azadirachtin-based products against M. alternatus and other target Coleoptera. These results further enhance the value of azadirachtin as a potential insecticide of biological origin, as well as for other biological applications.

Identification of differentially expressed genes in Monochamus alternatus digested with azadirachtin

PubMed Central

Lin, Tong; Liu, Qisi; Chen, Jingxiang

2016-01-01

The pine sawyer beetle Monochamus alternatus Hope, a major forest insect pest, is the primary vector of the destructive forest pest pine wood nematode, Bursaphelenchus xylophilus. Azadirachtin, an active compound of neem, is biologically interesting because it represents a group of important, successful botanical pesticides. We provide insight into the molecular effects of azadirachtin on M. alternatus at the transcriptional level to provide clues about possible molecular-level targets and to establish a link between azadirachtin and insect global responses. We found that 920 and 9894 unique genes were significantly up- and down-regulated, respectively. We obtained expression patterns of the differentially expressed genes (DEGs), identifying 4247, 3488 and 7613 sequences that involved cellular components, molecular functions and biological processes, respectively, and showed that the DEGs were distributed among 50 Gene Ontology categories. The Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were enriched in 50 pathways. Detailed gene profile knowledge of the interaction of azadirachtin with M. alternatus should facilitate the development of more effective azadirachtin-based products against M. alternatus and other target Coleoptera. These results further enhance the value of azadirachtin as a potential insecticide of biological origin, as well as for other biological applications. PMID:27629396

Understanding system dynamics of an adaptive enzyme network from globally profiled kinetic parameters.

PubMed

Chiang, Austin W T; Liu, Wei-Chung; Charusanti, Pep; Hwang, Ming-Jing

2014-01-15

A major challenge in mathematical modeling of biological systems is to determine how model parameters contribute to systems dynamics. As biological processes are often complex in nature, it is desirable to address this issue using a systematic approach. Here, we propose a simple methodology that first performs an enrichment test to find patterns in the values of globally profiled kinetic parameters with which a model can produce the required system dynamics; this is then followed by a statistical test to elucidate the association between individual parameters and different parts of the system's dynamics. We demonstrate our methodology on a prototype biological system of perfect adaptation dynamics, namely the chemotaxis model for Escherichia coli. Our results agreed well with those derived from experimental data and theoretical studies in the literature. Using this model system, we showed that there are motifs in kinetic parameters and that these motifs are governed by constraints of the specified system dynamics. A systematic approach based on enrichment statistical tests has been developed to elucidate the relationships between model parameters and the roles they play in affecting system dynamics of a prototype biological network. The proposed approach is generally applicable and therefore can find wide use in systems biology modeling research.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Knowledge Driven Variable Selection (KDVS) – a new approach to enrichment analysis of gene signatures obtained from high–throughput data

PubMed Central

2013-01-01

Background High–throughput (HT) technologies provide huge amount of gene expression data that can be used to identify biomarkers useful in the clinical practice. The most frequently used approaches first select a set of genes (i.e. gene signature) able to characterize differences between two or more phenotypical conditions, and then provide a functional assessment of the selected genes with an a posteriori enrichment analysis, based on biological knowledge. However, this approach comes with some drawbacks. First, gene selection procedure often requires tunable parameters that affect the outcome, typically producing many false hits. Second, a posteriori enrichment analysis is based on mapping between biological concepts and gene expression measurements, which is hard to compute because of constant changes in biological knowledge and genome analysis. Third, such mapping is typically used in the assessment of the coverage of gene signature by biological concepts, that is either score–based or requires tunable parameters as well, limiting its power. Results We present Knowledge Driven Variable Selection (KDVS), a framework that uses a priori biological knowledge in HT data analysis. The expression data matrix is transformed, according to prior knowledge, into smaller matrices, easier to analyze and to interpret from both computational and biological viewpoints. Therefore KDVS, unlike most approaches, does not exclude a priori any function or process potentially relevant for the biological question under investigation. Differently from the standard approach where gene selection and functional assessment are applied independently, KDVS embeds these two steps into a unified statistical framework, decreasing the variability derived from the threshold–dependent selection, the mapping to the biological concepts, and the signature coverage. We present three case studies to assess the usefulness of the method. Conclusions We showed that KDVS not only enables the selection of known biological functionalities with accuracy, but also identification of new ones. An efficient implementation of KDVS was devised to obtain results in a fast and robust way. Computing time is drastically reduced by the effective use of distributed resources. Finally, integrated visualization techniques immediately increase the interpretability of results. Overall, KDVS approach can be considered as a viable alternative to enrichment–based approaches. PMID:23302187

An efficient process for wastewater treatment to mitigate free nitrous acid generation and its inhibition on biological phosphorus removal

PubMed Central

Zhao, Jianwei; Wang, Dongbo; Li, Xiaoming; Yang, Qi; Chen, Hongbo; Zhong, Yu; An, Hongxue; Zeng, Guangming

2015-01-01

Free nitrous acid (FNA), which is the protonated form of nitrite and inevitably produced during biological nitrogen removal, has been demonstrated to strongly inhibit the activity of polyphosphate accumulating organisms (PAOs). Herein we reported an efficient process for wastewater treatment, i.e., the oxic/anoxic/oxic/extended-idle process to mitigate the generation of FNA and its inhibition on PAOs. The results showed that this new process enriched more PAOs which thereby achieved higher phosphorus removal efficiency than the conventional four-step (i.e., anaerobic/oxic/anoxic/oxic) biological nutrient removal process (41 ± 7% versus 30 ± 5% in abundance of PAOs and 97 ± 0.73% versus 82 ± 1.2% in efficiency of phosphorus removal). It was found that this new process increased pH value but decreased nitrite accumulation, resulting in the decreased FNA generation. Further experiments showed that the new process could alleviate the inhibition of FNA on the metabolisms of PAOs even under the same FNA concentration. PMID:25721019

Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform.

PubMed

Hur, Junguk; Danes, Larson; Hsieh, Jui-Hua; McGregor, Brett; Krout, Dakota; Auerbach, Scott

2018-05-01

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human-relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high-throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration-response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over-represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PathJam: a new service for integrating biological pathway information.

PubMed

Glez-Peña, Daniel; Reboiro-Jato, Miguel; Domínguez, Rubén; Gómez-López, Gonzalo; Pisano, David G; Fdez-Riverola, Florentino

2010-10-28

Biological pathways are crucial to much of the scientific research today including the study of specific biological processes related with human diseases. PathJam is a new comprehensive and freely accessible web-server application integrating scattered human pathway annotation from several public sources. The tool has been designed for both (i) being intuitive for wet-lab users providing statistical enrichment analysis of pathway annotations and (ii) giving support to the development of new integrative pathway applications. PathJam’s unique features and advantages include interactive graphs linking pathways and genes of interest, downloadable results in fully compatible formats, GSEA compatible output files and a standardized RESTful API.

[Problems of world outlook and methodology of science integration in biological studies].

PubMed

Khododova, Iu D

1981-01-01

Problems of worldoutlook and methodology of the natural-science knowledge are considered basing on the analysis of tendencies in the development of the membrane theory of cell processes and the use of principles of biological membrane functioning when solving some scientific and applied problems pertaining to different branches of chemistry and biology. The notion scientific knowledge integration is defined as interpenetration of approaches, methods and ideas of different branches of knowledge and enrichment on this basis of their content resulting in knowledge augmentation in each field taken separately. These processes are accompanied by appearance of new branches of knowledge - sciences "on junction" and their subsequent differentiations. The analysis of some gnoseological situations shows that integration of sciences contributes to coordination and some agreement of thinking styles of different specialists, puts forward keen personality of a scientist demanding, in particular, his high professional mobility. Problems of scientific activity organization are considered, which involve social sciences into the integration processes. The role of philosophy in the integration processes is emphasized.

Do two machine-learning based prognostic signatures for breast cancer capture the same biological processes?

PubMed

Drier, Yotam; Domany, Eytan

2011-03-14

The fact that there is very little if any overlap between the genes of different prognostic signatures for early-discovery breast cancer is well documented. The reasons for this apparent discrepancy have been explained by the limits of simple machine-learning identification and ranking techniques, and the biological relevance and meaning of the prognostic gene lists was questioned. Subsequently, proponents of the prognostic gene lists claimed that different lists do capture similar underlying biological processes and pathways. The present study places under scrutiny the validity of this claim, for two important gene lists that are at the focus of current large-scale validation efforts. We performed careful enrichment analysis, controlling the effects of multiple testing in a manner which takes into account the nested dependent structure of gene ontologies. In contradiction to several previous publications, we find that the only biological process or pathway for which statistically significant concordance can be claimed is cell proliferation, a process whose relevance and prognostic value was well known long before gene expression profiling. We found that the claims reported by others, of wider concordance between the biological processes captured by the two prognostic signatures studied, were found either to be lacking statistical rigor or were in fact based on addressing some other question.

Comparison of the gene expression profiles between gallstones and gallbladder polyps.

PubMed

Li, Quanfu; Ge, Xin; Xu, Xu; Zhong, Yonggang; Qie, Zengwang

2014-01-01

Gallstones and gallbladder polyps (GPs) are two major types of gallbladder diseases that share multiple common symptoms. However, their pathological mechanism remains largely unknown. The aim of our study is to identify gallstones and GPs related-genes and gain an insight into the underlying genetic basis of these diseases. We enrolled 7 patients with gallstones and 2 patients with GP for RNA-Seq and we conducted functional enrichment analysis and protein-protein interaction (PPI) networks analysis for identified differentially expressed genes (DEGs). RNA-Seq produced 41.7 million in gallstones and 32.1 million pairs in GPs. A total of 147 DEGs was identified between gallstones and GPs. We found GO terms for molecular functions significantly enriched in antigen binding (GO:0003823, P=5.9E-11), while for biological processes, the enriched GO terms were immune response (GO:0006955, P=2.6E-15), and for cellular component, the enriched GO terms were extracellular region (GO:0005576, P=2.7E-15). To further evaluate the biological significance for the DEGs, we also performed the KEGG pathway enrichment analysis. The most significant pathway in our KEGG analysis was Cytokine-cytokine receptor interaction (P=7.5E-06). PPI network analysis indicated that the significant hub proteins containing S100A9 (S100 calcium binding protein A9, Degree=94) and CR2 (complement component receptor 2, Degree=8). This present study suggests some promising genes and may provide a clue to the role of these genes playing in the development of gallstones and GPs.

Affinity Proteomics for Fast, Sensitive, Quantitative Analysis of Proteins in Plasma.

PubMed

O'Grady, John P; Meyer, Kevin W; Poe, Derrick N

2017-01-01

The improving efficacy of many biological therapeutics and identification of low-level biomarkers are driving the analytical proteomics community to deal with extremely high levels of sample complexity relative to their analytes. Many protein quantitation and biomarker validation procedures utilize an immunoaffinity enrichment step to purify the sample and maximize the sensitivity of the corresponding liquid chromatography tandem mass spectrometry measurements. In order to generate surrogate peptides with better mass spectrometric properties, protein enrichment is followed by a proteolytic cleavage step. This is often a time-consuming multistep process. Presented here is a workflow which enables rapid protein enrichment and proteolytic cleavage to be performed in a single, easy-to-use reactor. Using this strategy Klotho, a low-abundance biomarker found in plasma, can be accurately quantitated using a protocol that takes under 5 h from start to finish.

Cancer Cell Biology: A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science

PubMed Central

Bockholt, Susanne M.; West, J. Paige; Bollenbacher, Walter E.

2003-01-01

Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential “multimedia pedagogy” for the development of other multimedia science learning environments. PMID:12822037

Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis.

PubMed

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M

2009-06-29

One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a new pathway-level analysis scheme for integrative and comparative analysis of data derived from different but relevant systems. The tool is freely available as a Pathway Pattern Extraction Pipeline implemented in our existing software package WPS, which can be obtained at http://www.abcc.ncifcrf.gov/wps/wps_index.php.

Detecting phenotype-driven transitions in regulatory network structure.

PubMed

Padi, Megha; Quackenbush, John

2018-01-01

Complex traits and diseases like human height or cancer are often not caused by a single mutation or genetic variant, but instead arise from functional changes in the underlying molecular network. Biological networks are known to be highly modular and contain dense "communities" of genes that carry out cellular processes, but these structures change between tissues, during development, and in disease. While many methods exist for inferring networks and analyzing their topologies separately, there is a lack of robust methods for quantifying differences in network structure. Here, we describe ALPACA (ALtered Partitions Across Community Architectures), a method for comparing two genome-scale networks derived from different phenotypic states to identify condition-specific modules. In simulations, ALPACA leads to more nuanced, sensitive, and robust module discovery than currently available network comparison methods. As an application, we use ALPACA to compare transcriptional networks in three contexts: angiogenic and non-angiogenic subtypes of ovarian cancer, human fibroblasts expressing transforming viral oncogenes, and sexual dimorphism in human breast tissue. In each case, ALPACA identifies modules enriched for processes relevant to the phenotype. For example, modules specific to angiogenic ovarian tumors are enriched for genes associated with blood vessel development, and modules found in female breast tissue are enriched for genes involved in estrogen receptor and ERK signaling. The functional relevance of these new modules suggests that not only can ALPACA identify structural changes in complex networks, but also that these changes may be relevant for characterizing biological phenotypes.

Molecular cloning and expression analysis of the retinoid X receptor (RXR) gene in golden pompano Trachinotus ovatus fed Artemia nauplii with different enrichments.

PubMed

Yang, Qibin; Zheng, Panlong; Ma, Zhenhua; Li, Tao; Jiang, Shigui; Qin, Jian G

2015-12-01

The retinoid X receptors (RXRs) are involved in the skeletal development and other biological process such as blood vessel formation and metabolism. Partial sequences of RXRα and β genes were obtained, and their expressions were quantified on golden pompano Trachinotus ovatus at 28 days post hatching (DPH) to explore the molecular response to nutritional manipulation in fish larvae. As live food, Artemia nauplii were separately enriched with Nannochloropsis and Algamac 3080 and non-enriched Artemia nauplii (control) for fish feeding. The expressions of RXRs were detected in the embryos and fish larvae at early stages, suggesting that the skeletal development in golden pompano initiated before yolk re-sorption completion. Fish fed non-enriched Artemia nauplii ended up with higher jaw malformation. The highest specific growth rate was obtained when fish were fed with the Artemia nauplii enriched with Algamac 3080, and the lowest growth rate was observed when fish were fed with unenriched Artemia nauplii. The highest survival was obtained when fish were fed with non-enriched or Nannochloropsis-enriched Artemia nauplii. This study indicates that the use of enriched formula for Artemia nauplii can significantly affect the expression levels of RXRs and jaw malformation of golden pompano larvae, but there is no clear correlation between RXRs expressions and malformation rates when fish are subjected to nutrient challenge.

A Pharmacology-Based Enrichment Program for Undergraduates Promotes Interest in Science

PubMed Central

Godin, Elizabeth A.; Wormington, Stephanie V.; Perez, Tony; Barger, Michael M.; Snyder, Kate E.; Richman, Laura Smart; Schwartz-Bloom, Rochelle; Linnenbrink-Garcia, Lisa

2015-01-01

There is a strong need to increase the number of undergraduate students who pursue careers in science to provide the “fuel” that will power a science and technology–driven U.S. economy. Prior research suggests that both evidence-based teaching methods and early undergraduate research experiences may help to increase retention rates in the sciences. In this study, we examined the effect of a program that included 1) a Summer enrichment 2-wk minicourse and 2) an authentic Fall research course, both of which were designed specifically to support students' science motivation. Undergraduates who participated in the pharmacology-based enrichment program significantly improved their knowledge of basic biology and chemistry concepts; reported high levels of science motivation; and were likely to major in a biological, chemical, or biomedical field. Additionally, program participants who decided to major in biology or chemistry were significantly more likely to choose a pharmacology concentration than those majoring in biology or chemistry who did not participate in the enrichment program. Thus, by supporting students' science motivation, we can increase the number of students who are interested in science and science careers. PMID:26538389

Impact of constitutional copy number variants on biological pathway evolution.

PubMed

Poptsova, Maria; Banerjee, Samprit; Gokcumen, Omer; Rubin, Mark A; Demichelis, Francesca

2013-01-23

Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

Impact of constitutional copy number variants on biological pathway evolution

PubMed Central

2013-01-01

Background Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. Results We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. Conclusions The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations. PMID:23342974

Identification of protein features encoded by alternative exons using Exon Ontology.

PubMed

Tranchevent, Léon-Charles; Aubé, Fabien; Dulaurier, Louis; Benoit-Pilven, Clara; Rey, Amandine; Poret, Arnaud; Chautard, Emilie; Mortada, Hussein; Desmet, François-Olivier; Chakrama, Fatima Zahra; Moreno-Garcia, Maira Alejandra; Goillot, Evelyne; Janczarski, Stéphane; Mortreux, Franck; Bourgeois, Cyril F; Auboeuf, Didier

2017-06-01

Transcriptomic genome-wide analyses demonstrate massive variation of alternative splicing in many physiological and pathological situations. One major challenge is now to establish the biological contribution of alternative splicing variation in physiological- or pathological-associated cellular phenotypes. Toward this end, we developed a computational approach, named "Exon Ontology," based on terms corresponding to well-characterized protein features organized in an ontology tree. Exon Ontology is conceptually similar to Gene Ontology-based approaches but focuses on exon-encoded protein features instead of gene level functional annotations. Exon Ontology describes the protein features encoded by a selected list of exons and looks for potential Exon Ontology term enrichment. By applying this strategy to exons that are differentially spliced between epithelial and mesenchymal cells and after extensive experimental validation, we demonstrate that Exon Ontology provides support to discover specific protein features regulated by alternative splicing. We also show that Exon Ontology helps to unravel biological processes that depend on suites of coregulated alternative exons, as we uncovered a role of epithelial cell-enriched splicing factors in the AKT signaling pathway and of mesenchymal cell-enriched splicing factors in driving splicing events impacting on autophagy. Freely available on the web, Exon Ontology is the first computational resource that allows getting a quick insight into the protein features encoded by alternative exons and investigating whether coregulated exons contain the same biological information. © 2017 Tranchevent et al.; Published by Cold Spring Harbor Laboratory Press.

Toluene in sewage and sludge in wastewater treatment plants.

PubMed

Mrowiec, Bozena

2014-01-01

Toluene is a compound that often occurs in municipal wastewater ranging from detectable levels up to 237 μg/L. Before the year 2000, the presence of the aromatic hydrocarbons was assigned only to external sources. The Enhanced Biological Nutrients Removal Processes (EBNRP) work according to many different schemes and technologies. For high-efficiency biological denitrification and dephosphatation processes, the presence of volatile fatty acids (VFAs) in sewage is required. VFAs are the main product of organic matter hydrolysis from sewage sludge. However, no attention has been given to other products of the process. It has been found that in parallel to VFA production, toluene formation occurred. The formation of toluene in municipal anaerobic sludge digestion processes was investigated. Experiments were performed on a laboratory scale using sludge from primary and secondary settling tanks of municipal treatment plants. The concentration of toluene in the digested sludge from primary settling tanks was found to be about 42,000 μg/L. The digested sludge supernatant liquor returned to the biological dephosphatation and denitrification processes for sewage enrichment can contain up to 16,500 μg/L of toluene.

Comparative Toxicogenomic Responses to the Flame Retardant mITP in Developing Zebrafish.

PubMed

Haggard, Derik E; Das, Siba R; Tanguay, Robert L

2017-02-20

Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping failure. Mechanistic studies showed that mITP is an aryl hydrocarbon receptor (AhR) ligand; however, the cardiotoxic effects of mITP were independent of the AhR. We performed comparative whole genome transcriptomics in wild-type and ahr2 hu3335 zebrafish, which lack functional ahr2, to identify transcriptional signatures causally involved in the mechanism of mITP-induced cardiotoxicity. Regardless of ahr2 status, mITP exposure resulted in decreased expression of transcripts related to the synthesis of all-trans-retinoic acid and a host of Hox genes. Clustered gene ontology enrichment analysis showed unique enrichment in biological processes related to xenobiotic metabolism and response to external stimuli in wild-type samples. Transcript enrichments overlapping both genotypes involved the retinoid metabolic process and sensory/visual perception biological processes. Examination of the gene-gene interaction network of the differentially expressed transcripts in both genetic backgrounds demonstrated a strong AhR interaction network specific to wild-type samples, with overlapping genes regulated by retinoic acid receptors (RARs). A transcriptome analysis of control ahr2-null zebrafish identified potential cross-talk among AhR, Nrf2, and Hif1α. Collectively, we confirmed that mITP is an AhR ligand and present evidence in support of our hypothesis that mITP's developmental cardiotoxic effects are mediated by inhibition at the RAR level.

Reconnaissance Report on Papillion Creek Reservoirs.

DTIC Science & Technology

1981-03-01

The appearance of the reservoir and production of malodors are nonaesthetic. The general charateristics of the flood control reservoirs near Lincoln...characteristic of extremely unproductive soft transparent waters to extremely productive hard waters turbid with plankton. A more current trend in lake...quality and biological productivity . The process of nutrient enrichment does not always result in the degradation of water quality. Whether or not the

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line.

PubMed

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R; Shen, Han-Ming; Lin, Qingsong

2016-02-26

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQ(TM) quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway Analysis(TM) (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death.

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

PubMed Central

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R.; Shen, Han-Ming; Lin, Qingsong

2016-01-01

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQTM quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway AnalysisTM (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death. PMID:26915414

Transcriptome differences between enrofloxacin-resistant and enrofloxacin-susceptible strains of Aeromonas hydrophila.

PubMed

Zhu, Fengjiao; Yang, Zongying; Zhang, Yiliu; Hu, Kun; Fang, Wenhong

2017-01-01

Enrofloxacin is the most commonly used antibiotic to control diseases in aquatic animals caused by A. hydrophila. This study conducted de novo transcriptome sequencing and compared the global transcriptomes of enrofloxacin-resistant and enrofloxacin-susceptible strains. We got a total of 4,714 unigenes were assembled. Of these, 4,122 were annotated. A total of 3,280 unigenes were assigned to GO, 3,388 unigenes were classified into Cluster of Orthologous Groups of proteins (COG) using BLAST and BLAST2GO software, and 2,568 were mapped onto pathways using the Kyoto Encyclopedia of Gene and Genomes Pathway database. Furthermore, 218 unigenes were deemed to be DEGs. After enrofloxacin treatment, 135 genes were upregulated and 83 genes were downregulated. The GO terms biological process (126 genes) and metabolic process (136 genes) were the most enriched, and the terms for protein folding, response to stress, and SOS response were also significantly enriched. This study identified enrofloxacin treatment affects multiple biological functions of A. hydrophila. Enrofloxacin resistance in A. hydrophila is closely related to the reduction of intracellular drug accumulation caused by ABC transporters and increased expression of topoisomerase IV.

Transcriptome differences between enrofloxacin-resistant and enrofloxacin-susceptible strains of Aeromonas hydrophila

PubMed Central

Yang, Zongying; Zhang, Yiliu; Hu, Kun; Fang, Wenhong

2017-01-01

Enrofloxacin is the most commonly used antibiotic to control diseases in aquatic animals caused by A. hydrophila. This study conducted de novo transcriptome sequencing and compared the global transcriptomes of enrofloxacin-resistant and enrofloxacin-susceptible strains. We got a total of 4,714 unigenes were assembled. Of these, 4,122 were annotated. A total of 3,280 unigenes were assigned to GO, 3,388 unigenes were classified into Cluster of Orthologous Groups of proteins (COG) using BLAST and BLAST2GO software, and 2,568 were mapped onto pathways using the Kyoto Encyclopedia of Gene and Genomes Pathway database. Furthermore, 218 unigenes were deemed to be DEGs. After enrofloxacin treatment, 135 genes were upregulated and 83 genes were downregulated. The GO terms biological process (126 genes) and metabolic process (136 genes) were the most enriched, and the terms for protein folding, response to stress, and SOS response were also significantly enriched. This study identified enrofloxacin treatment affects multiple biological functions of A. hydrophila. Enrofloxacin resistance in A. hydrophila is closely related to the reduction of intracellular drug accumulation caused by ABC transporters and increased expression of topoisomerase IV. PMID:28708867

Defining the optimal animal model for translational research using gene set enrichment analysis.

PubMed

Weidner, Christopher; Steinfath, Matthias; Opitz, Elisa; Oelgeschläger, Michael; Schönfelder, Gilbert

2016-08-01

The mouse is the main model organism used to study the functions of human genes because most biological processes in the mouse are highly conserved in humans. Recent reports that compared identical transcriptomic datasets of human inflammatory diseases with datasets from mouse models using traditional gene-to-gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. To reduce susceptibility to biased interpretation, all genes of interest for the biological question under investigation should be considered. Thus, standardized approaches for systematic data analysis are needed. We analyzed the same datasets using gene set enrichment analysis focusing on pathways assigned to inflammatory processes in either humans or mice. The analyses revealed a moderate overlap between all human and mouse datasets, with average positive and negative predictive values of 48 and 57% significant correlations. Subgroups of the septic mouse models (i.e., Staphylococcus aureus injection) correlated very well with most human studies. These findings support the applicability of targeted strategies to identify the optimal animal model and protocol to improve the success of translational research. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Application of Oxygen-Enriched Aeration in the Production of Bacitracin by Bacillus licheniformis

PubMed Central

Flickinger, M. C.; Perlman, D.

1979-01-01

The physiological effects of controlling the dissolved oxygen tension at 0.01, 0.02, and 0.05 atm by the use of oxygen-enriched aeration were investigated during growth and bacitracin production by Bacillus licheniformis ATCC 10716. Up to a 2.35-fold increase in the final antibiotic yield and a 4-fold increase in the rate of bacitracin synthesis were observed in response to O2-enriched aeration. The increase in antibiotic production was accompanied by increased respiratory activity and an increase in the specific productivity of the culture from 1.3 to 3.6 g of antibiotic per g of cell mass produced. Oxygen enrichment of the aeration decreased medium carbohydrate uptake and the maximum specific growth rate of B. licheniformis from 0.6 h−1 to as low as 0.15 h−1, depending upon the level of enrichment and the conditions of oxygen transfer rate (impeller speed). The response of this culture to O2 enrichment suggests that this method of controlling the dissolved oxygen tension for antibiotic-producing cultures may simulate conditions that would occur if the carbon source were fed slowly, as is often employed to optimize antibiotic production. Analysis of the biologically active bacitracins produced by B. licheniformis ATCC 10716 suggested that the ratio of biologically active peptides was not changed by O2 enrichment, nor were any new biologically active compounds formed. Images PMID:34361

Effect of inoculum sources on the enrichment of nitrite-dependent anaerobic methane-oxidizing bacteria.

PubMed

He, Zhanfei; Cai, Chen; Shen, Lidong; Lou, Liping; Zheng, Ping; Xu, Xinhua; Hu, Baolan

2015-01-01

Nitrite-dependent anaerobic methane oxidation (n-damo) is a newly discovered biological process that couples anaerobic oxidation of methane (AOM) to nitrite reduction. In this study, three different inocula, methanogenic sludge, paddy soil, and freshwater sediment were used to enrich n-damo bacteria in three sequencing batch reactors (SBRs), and three n-damo enrichment cultures, C1, C2 and C3, were obtained, respectively. After 500 days of incubation, Methylomirabilis oxyfera-like bacteria and n-damo activities were observed in cultures C1, C2, and C3, and the specific activities were 0.8 ± 0.1, 1.4 ± 0.1, and 1.0 ± 0.1 μmol CH4 h(-1) g(-1) VSS, respectively. The copy numbers of 16S rRNA genes from cultures C1, C2, and C3 were 5.0 ± 0.4 × 10(8), 6.1 ± 0.1 × 10(9), and 1.0 ± 0.2 × 10(9) copies g(-1) dry weight, respectively. The results indicated that paddy soil is an excellent inoculum for n-damo bacterial enrichment. This work expanded the alternative source of n-damo inoculum and benefited the further research of n-damo process.

De novo transcriptome assembly and identification of genes associated with feed conversion ratio and breast muscle yield in domestic ducks.

PubMed

Zhu, Feng; Yuan, Jian-Ming; Zhang, Zhen-He; Hao, Jin-Ping; Yang, Yu-Ze; Hu, Shen-Qiang; Yang, Fang-Xi; Qu, Lu-Jiang; Hou, Zhuo-Cheng

2015-12-01

Breast muscle yield and feed conversion efficiency are the major breeding aims in duck breeding. Understanding the role of specific transcripts in the muscle and small intestine might lead to the elucidation of interrelated biological processes. In this study, we obtained jejunum and breast muscle samples from two strains of Peking ducks that were sorted by feed conversion ratio (FCR) and breast muscle percentage into two-tailed populations. Ten RNA-Seq libraries were developed from the pooled samples and sequenced using the Hiseq2000 platform. We created a reference duck transcript database using de novo assembly methods, which included 16 663 irredundant contigs with an N50 length of 1530 bp. This new duck reference cDNA dataset significantly improved the mapping rate for RNA-Seq data, from 50% to 70%. Mapping and annotation were followed by Gene Ontology analysis, which showed that numerous genes were differentially expressed between the low and high FCR groups. The differentially expressed genes in the jejunum were enriched in biological processes related to immune response and immune response activation, whereas those in the breast muscle were significantly enriched in biological processes related to muscle cell differentiation and organ development. We identified new candidate genes, that is, PCK1, for improving the FCR and breast muscle yield of ducks and obtained much better reference duck transcripts. This study suggested that de novo assembly is essential when applying transcriptome analysis to a species with an incomplete genome. © 2015 Stichting International Foundation for Animal Genetics.

Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

PubMed

Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

2015-08-01

We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

Specific enrichment of a targeted nitrotyrosine-containing peptide from complex matrices and relative quantification for liquid chromatography-mass spectrometry analysis.

PubMed

Yang, Yun

2017-02-17

Protein tyrosine nitration is considered an important non-enzymatic post-translational modification. In the tyrosine nitration process, 3-nitrotyrosine is formed and recognized as a biomarker of nitrosative/nitrative stress implicated in inflammatory responses and age-related disorders. In view of the complexity of biological samples and the ultra-low abundance of protein-incorporated nitrotyrosine, selective enrichment of nitrotyrosine-containing peptides prior to chromatographic separation is crucial. Herein, I report a simple yet highly specific and efficient enrichment method for nitrotyrosine-containing peptides. After blocking all primary amines in the sample by acetylation with acetic anhydride, I then further converted all nitrotyrosine residues into aminotyrosine residues by reduction with dithiothreitol and hemin. Therefore, I eliminated the side-product with 80Da adduct, since inevitable considerable amount of which was generated in the widely used reduction mediated by sodium dithionite. Both acetylation and reduction yields were close to 100%, and my one-pot sample derivatization applied no solid phase extraction steps or sample transference to avoid sample loss. To capture and release aminotyrosine-containing peptides, I synthesized an N-hydroxysuccinimide-ester-functionalized stationary phase which had very high affinity towards amino groups and possessed a base-cleavable ester linker to retrieve targeted peptides by hydrolysis. I validated this strategy by highly efficient enrichment of the targeted peptide from complex matrices of trypsin-digested bovine serum albumin (BSA) and human plasma spiked with derivatized nitrotyrosine-containing angiotensin II. My enrichment method successfully removed most untargeted peptides in those samples. By relative quantification with home-made identical and stable-isotope labelled internal standards, I investigated the recoveries of a nitrotyrosine-containing peptide from complex biological matrices during enrichment for the first time. Mean recoveries were 49.8% and 41.1% (n=6) for the enrichment of nitrotyrosine-containing angiotensin II from 1:100 (w/w) BSA digest and from 1:10 000 (w/w) human plasma digest, respectively. My enrichment method demonstrated great potential in future applications to clinical samples and biomarker discovery. Copyright © 2017 Elsevier B.V. All rights reserved.

Primary marine aerosol physical flux and chemical composition during a nutrient enrichment experiment in mesocosms in the Mediterranean Sea

NASA Astrophysics Data System (ADS)

Schwier, Allison N.; Sellegri, Karine; Mas, Sébastien; Charrière, Bruno; Pey, Jorge; Rose, Clémence; Temime-Roussel, Brice; Jaffrezo, Jean-Luc; Parin, David; Picard, David; Ribeiro, Mickael; Roberts, Greg; Sempéré, Richard; Marchand, Nicolas; D'Anna, Barbara

2017-12-01

While primary marine aerosol (PMA) is an important part of global aerosol total emissions, its chemical composition and physical flux as a function of the biogeochemical properties of the seawater still remain highly uncharacterized due to the multiplicity of physical, chemical and biological parameters that are involved in the emission process. Here, two nutrient-enriched mesocosms and one control mesocosm, both filled with Mediterranean seawater, were studied over a 3-week period. PMA generated from the mesocosm waters were characterized in term of chemical composition, size distribution and size-segregated cloud condensation nuclei (CCN), as a function of the seawater chlorophyll a (Chl a) concentration, pigment composition, virus and bacteria abundances. The aerosol number size distribution flux was primarily affected by the seawater temperature and did not vary significantly from one mesocosm to the other. The aerosol number size distribution flux was primarily affected by the seawater temperature and did not vary significantly from one mesocosm to the other. Particle number and CCN aerosol fluxes increase by a factor of 2 when the temperature increases from 22 to 32 °C, for all particle submicron sizes. This effect, rarely observed in previous studies, could be specific to oligotrophic waters and/or to this temperature range. In all mesocosms (enriched and control mesocosms), we detected an enrichment of calcium (+500 %) and a deficit in chloride (-36 %) in the submicron PMA mass compared to the literature inorganic composition of the seawater. There are indications that the chloride deficit and calcium enrichment are linked to biological processes, as they are found to be stronger in the enriched mesocosms. This implies a non-linear transfer function between the seawater composition and PMA composition, with complex processes taking place at the interface during the bubble bursting. We found that the artificial phytoplankton bloom did not affect the CCN activation diameter (Dp, 50, average = 59.85±3.52 nm and Dp,50,average = 93.42±5.14 nm for supersaturations of 0.30 and 0.15 % respectively) or the organic fraction of the submicron PMA (average organic to total mass = 0.31±0.07) compared to the control mesocosm. Contrary to previous observations in natural bloom mesocosm experiments, the correlation between the particle organic fraction and the seawater Chl a was poor, indicating that Chl a is likely not a straightforward proxy for predicting, on a daily scale, PMA organic fraction in models for all types of sea and ocean waters. Instead, the organic fraction of the Aitken mode particles were more significantly linked to heterotrophic flagellates, viruses and dissolved organic carbon (DOC). We stress that different conclusions may be obtained in natural (non-enriched) or non-oligotrophic systems.

ProbCD: enrichment analysis accounting for categorization uncertainty.

PubMed

Vêncio, Ricardo Z N; Shmulevich, Ilya

2007-10-12

As in many other areas of science, systems biology makes extensive use of statistical association and significance estimates in contingency tables, a type of categorical data analysis known in this field as enrichment (also over-representation or enhancement) analysis. In spite of efforts to create probabilistic annotations, especially in the Gene Ontology context, or to deal with uncertainty in high throughput-based datasets, current enrichment methods largely ignore this probabilistic information since they are mainly based on variants of the Fisher Exact Test. We developed an open-source R-based software to deal with probabilistic categorical data analysis, ProbCD, that does not require a static contingency table. The contingency table for the enrichment problem is built using the expectation of a Bernoulli Scheme stochastic process given the categorization probabilities. An on-line interface was created to allow usage by non-programmers and is available at: http://xerad.systemsbiology.net/ProbCD/. We present an analysis framework and software tools to address the issue of uncertainty in categorical data analysis. In particular, concerning the enrichment analysis, ProbCD can accommodate: (i) the stochastic nature of the high-throughput experimental techniques and (ii) probabilistic gene annotation.

PSEA-Quant: a protein set enrichment analysis on label-free and label-based protein quantification data.

PubMed

Lavallée-Adam, Mathieu; Rauniyar, Navin; McClatchy, Daniel B; Yates, John R

2014-12-05

The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights.

PSEA-Quant: A Protein Set Enrichment Analysis on Label-Free and Label-Based Protein Quantification Data

PubMed Central

2015-01-01

The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights. PMID:25177766

Coupling of metal-organic frameworks-containing monolithic capillary-based selective enrichment with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry for efficient analysis of protein phosphorylation.

PubMed

Li, Daojin; Yin, Danyang; Chen, Yang; Liu, Zhen

2017-05-19

Protein phosphorylation is a major post-translational modification, which plays a vital role in cellular signaling of numerous biological processes. Mass spectrometry (MS) has been an essential tool for the analysis of protein phosphorylation, for which it is a key step to selectively enrich phosphopeptides from complex biological samples. In this study, metal-organic frameworks (MOFs)-based monolithic capillary has been successfully prepared as an effective sorbent for the selective enrichment of phosphopeptides and has been off-line coupled with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for efficient analysis of phosphopeptides. Using š-casein as a representative phosphoprotein, efficient phosphorylation analysis by this off-line platform was verified. Phosphorylation analysis of a nonfat milk sample was also demonstrated. Through introducing large surface areas and highly ordered pores of MOFs into monolithic column, the MOFs-based monolithic capillary exhibited several significant advantages, such as excellent selectivity toward phosphopeptides, superb tolerance to interference and simple operation procedure. Because of these highly desirable properties, the MOFs-based monolithic capillary could be a useful tool for protein phosphorylation analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Developing a test-bed for robust research governance of geoengineering: the contribution of ocean iron biogeochemistry

PubMed Central

Bressac, Matthieu

2016-01-01

Geoengineering to mitigate climate change has long been proposed, but remains nebulous. Exploration of the feasibility of geoengineering first requires the development of research governance to move beyond the conceptual towards scientifically designed pilot studies. Fortuitously, 12 mesoscale (approx. 1000 km2) iron enrichments, funded to investigate how ocean iron biogeochemistry altered Earth's carbon cycle in the geological past, provide proxies to better understand the benefits and drawbacks of geoengineering. The utility of these iron enrichments in the geoengineering debate is enhanced by the GEOTRACES global survey. Here, we outline how GEOTRACES surveys and process studies can provide invaluable insights into geoengineering. Surveys inform key unknowns including the regional influence and magnitude of modes of iron supply, and stimulate iron biogeochemical modelling. These advances will enable quantification of interannual variability of iron supply to assess whether any future purposeful multi-year iron-fertilization meets the principle of ‘additionality’ (sensu Kyoto protocol). Process studies address issues including upscaling of geoengineering, and how differing iron-enrichment strategies could stimulate wide-ranging biogeochemical outcomes. In summary, the availability of databases on both mesoscale iron-enrichment studies and the GEOTRACES survey, along with modelling, policy initiatives and legislation have positioned the iron-enrichment approach as a robust multifaceted test-bed to assess proposed research into climate intervention. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’. PMID:29035263

Developing a test-bed for robust research governance of geoengineering: the contribution of ocean iron biogeochemistry.

PubMed

Boyd, Philip W; Bressac, Matthieu

2016-11-28

Geoengineering to mitigate climate change has long been proposed, but remains nebulous. Exploration of the feasibility of geoengineering first requires the development of research governance to move beyond the conceptual towards scientifically designed pilot studies. Fortuitously, 12 mesoscale (approx. 1000 km 2 ) iron enrichments, funded to investigate how ocean iron biogeochemistry altered Earth's carbon cycle in the geological past, provide proxies to better understand the benefits and drawbacks of geoengineering. The utility of these iron enrichments in the geoengineering debate is enhanced by the GEOTRACES global survey. Here, we outline how GEOTRACES surveys and process studies can provide invaluable insights into geoengineering. Surveys inform key unknowns including the regional influence and magnitude of modes of iron supply, and stimulate iron biogeochemical modelling. These advances will enable quantification of interannual variability of iron supply to assess whether any future purposeful multi-year iron-fertilization meets the principle of 'additionality' ( sensu Kyoto protocol). Process studies address issues including upscaling of geoengineering, and how differing iron-enrichment strategies could stimulate wide-ranging biogeochemical outcomes. In summary, the availability of databases on both mesoscale iron-enrichment studies and the GEOTRACES survey, along with modelling, policy initiatives and legislation have positioned the iron-enrichment approach as a robust multifaceted test-bed to assess proposed research into climate intervention.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'. © 2016 The Author(s).

Clinical relevance and biology of circulating tumor cells

PubMed Central

2011-01-01

Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

Enhanced degradation of phenolic compounds in coal gasification wastewater by a novel integration of micro-electrolysis with biological reactor (MEBR) under the micro-oxygen condition.

PubMed

Ma, Weiwei; Han, Yuxing; Xu, Chunyan; Han, Hongjun; Ma, Wencheng; Zhu, Hao; Li, Kun; Wang, Dexin

2018-03-01

The aim of this work was to study an integration of micro-electrolysis with biological reactor (MEBR) for strengthening removal of phenolic compounds in coal gasification wastewater (CGW). The results indicated MEBR achieved high efficiencies in removal of COD and phenolic compounds as well as improvement of biodegradability of CGW under the micro-oxygen condition. The integrated MEBR process was more favorable to improvement of the structural stability of activated sludge and biodiversity of specific functional microbial communities. Especially, Shewanella and Pseudomonas were enriched to accelerate the extracellular electron transfer, finally facilitating the degradation of phenolic compounds. Moreover, MEBR process effectively relieved passivation of Fe-C filler surface and prolonged lifespan of Fe-C filler. Accordingly, the synergetic effect between iron-carbon micro-electrolysis (ICME) and biological action played a significant role in performance of the integrated process. Therefore, the integrated MEBR was a promising practical process for enhancing CGW treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mining lipolytic enzymes in community DNA from high Andean soils using a targeted approach.

PubMed

Borda-Molina, Daniel; Montaña, José Salvador; Zambrano, María Mercedes; Baena, Sandra

2017-08-01

Microbial enrichments cultures are a useful strategy to speed up the search for enzymes that can be employed in industrial processes. Lipases have gained special attention because they show unique properties such as: broad substrate specificity, enantio- and regio-selectivity and stability in organic solvents. A major goal is to identify novel lipolytic enzymes from microorganisms living in cold extreme environments such as high Andean soils, of relevance to our study being their capability be used in industrial processes. Paramo and glacier soils from the Nevados National Park in Colombia were sampled and microbial communities enriched through a fed-batch fermentation using olive oil as an inductor substrate. After 15 days of enrichment under aerobic conditions, total DNA was extracted. Subsequently, metagenomic libraries were constructed in the cosmid vector pWEB-TNC™. After functional screening, twenty and eighteen lipolytic clones were obtained from Paramo and Glacier soil enrichments, respectively. Based on lipid hydrolysis halo dimensions, the clone (Gla1) from a glacier enrichment was selected. A gene related to lipolytic activity was subcloned to evaluate enzyme properties. Phylogenetic analysis of the identified gene showed that the encoded lipase belongs to the family GDSL from a Ralstonia-like species. Interestingly, the secreted enzyme exhibited stability at high temperature and alkaline conditions, specifically the preferred conditions at 80 °C and pH 9.0. Thus, with the identification of an enzyme with non-expected properties, in this study is shown the potential of extreme cold environments to be explored for new catalytic molecules, using current molecular biology techniques, with applications in industrial processes, which demand stability under harsh conditions.

Hydrophobic Properties of Biofilm-Enriched Hybrid Mortar.

PubMed

Grumbein, Stefan; Minev, Dionis; Tallawi, Marwa; Boettcher, Kathrin; Prade, Friedrich; Pfeiffer, Franz; Grosse, Christian Ulrich; Lieleg, Oliver

2016-10-01

A mortar hybrid material is presented in which biomineralization processes are stimulated by adding a biological component, i.e., bacterial biofilm, to standard mortar. A material is obtained that exhibits increased roughness on the microscale and the nanoscale. Accordingly, the hybrid mortar not only resists wetting but also suppresses the uptake of water by capillary forces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A large scale Plasmodium vivax- Saimiri boliviensis trophozoite-schizont transition proteome

PubMed Central

Lapp, Stacey A.; Barnwell, John W.; Galinski, Mary R.

2017-01-01

Plasmodium vivax is a complex protozoan parasite with over 6,500 genes and stage-specific differential expression. Much of the unique biology of this pathogen remains unknown, including how it modifies and restructures the host reticulocyte. Using a recently published P. vivax reference genome, we report the proteome from two biological replicates of infected Saimiri boliviensis host reticulocytes undergoing transition from the late trophozoite to early schizont stages. Using five database search engines, we identified a total of 2000 P. vivax and 3487 S. boliviensis proteins, making this the most comprehensive P. vivax proteome to date. PlasmoDB GO-term enrichment analysis of proteins identified at least twice by a search engine highlighted core metabolic processes and molecular functions such as glycolysis, translation and protein folding, cell components such as ribosomes, proteasomes and the Golgi apparatus, and a number of vesicle and trafficking related clusters. Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 enriched functional annotation clusters of S. boliviensis proteins highlighted vesicle and trafficking-related clusters, elements of the cytoskeleton, oxidative processes and response to oxidative stress, macromolecular complexes such as the proteasome and ribosome, metabolism, translation, and cell death. Host and parasite proteins potentially involved in cell adhesion were also identified. Over 25% of the P. vivax proteins have no functional annotation; this group includes 45 VIR members of the large PIR family. A number of host and pathogen proteins contained highly oxidized or nitrated residues, extending prior trophozoite-enriched stage observations from S. boliviensis infections, and supporting the possibility of oxidative stress in relation to the disease. This proteome significantly expands the size and complexity of the known P. vivax and Saimiri host iRBC proteomes, and provides in-depth data that will be valuable for ongoing research on this parasite’s biology and pathogenesis. PMID:28829774

Global Proteome Analyses of Lysine Acetylation and Succinylation Reveal the Widespread Involvement of both Modification in Metabolism in the Embryo of Germinating Rice Seed.

PubMed

He, Dongli; Wang, Qiong; Li, Ming; Damaris, Rebecca Njeri; Yi, Xingling; Cheng, Zhongyi; Yang, Pingfang

2016-03-04

Regulation of rice seed germination has been shown to mainly occur at post-transcriptional levels, of which the changes on proteome status is a major one. Lysine acetylation and succinylation are two prevalent protein post-translational modifications (PTMs) involved in multiple biological processes, especially for metabolism regulation. To investigate the potential mechanism controlling metabolism regulation in rice seed germination, we performed the lysine acetylation and succinylation analyses simultaneously. Using high-accuracy nano-LC-MS/MS in combination with the enrichment of lysine acetylated or succinylated peptides from digested embryonic proteins of 24 h after imbibition (HAI) rice seed, a total of 699 acetylated sites from 389 proteins and 665 succinylated sites from 261 proteins were identified. Among these modified lysine sites, 133 sites on 78 proteins were commonly modified by two PTMs. The overlapped PTM sites were more likely to be in polar acidic/basic amino acid regions and exposed on the protein surface. Both of the acetylated and succinylated proteins cover nearly all aspects of cellular functions. Ribosome complex and glycolysis/gluconeogenesis-related proteins were significantly enriched in both acetylated and succinylated protein profiles through KEGG enrichment and protein-protein interaction network analyses. The acetyl-CoA and succinyl-CoA metabolism-related enzymes were found to be extensively modified by both modifications, implying the functional interaction between the two PTMs. This study provides a rich resource to examine the modulation of the two PTMs on the metabolism pathway and other biological processes in germinating rice seed.

Smoke-related DNA methylation changes in the etiology of human disease.

PubMed

Besingi, Welisane; Johansson, Asa

2014-05-01

Exposure to environmental and lifestyle factors, such as cigarette smoking, affect the epigenome and might mediate risk for diseases and cancers. We have performed a genome-wide DNA methylation study to determine the effect of smoke and snuff (smokeless tobacco) on DNA methylation. A total of 95 sites were differentially methylated [false discovery rate (FDR) q-values < 0.05] in smokers and a subset of the differentially methylated loci were also differentially expressed in smokers. We found no sites, neither any biological functions nor molecular processes enriched for smoke-less tobacco-related differential DNA methylation. This suggests that methylation changes are not caused by the basic components of the tobacco but from its burnt products. Instead, we see a clear enrichment (FDR q-value < 0.05) for genes, including CPOX, CDKN1A and PTK2, involved in response to arsenic-containing substance, which agrees with smoke containing small amounts of arsenic. A large number of biological functions and molecular processes with links to disease conditions are also enriched (FDR q-value < 0.05) for smoke-related DNA methylation changes. These include 'insulin receptor binding', and 'negative regulation of glucose import' which are associated with diabetes, 'positive regulation of interleukin-6-mediated signaling pathway', 'regulation of T-helper 2 cell differentiation', 'positive regulation of interleukin-13 production' which are associated with the immune system and 'sertoli cell fate commitment' which is important for male fertility. Since type 2 diabetes, repressed immune system and infertility have previously been associated with smoking, our results suggest that this might be mediated by DNA methylation changes.

Radiation Quality Effects on Transcriptome Profiles in 3-d Cultures After Particle Irradiation

NASA Technical Reports Server (NTRS)

Patel, Z. S.; Kidane, Y. H.; Huff, J. L.

2014-01-01

In this work, we evaluate the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Reducing uncertainties in current risk models requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. We are utilizing novel 3-D organotypic human tissue models that provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information. We identified 45 statistically significant gene sets at 0.05 q-value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to gamma irradiation, and 12 titanium-specific gene sets. Common gene sets largely align with DNA damage, cell cycle, early immune response, and inflammatory cytokine pathway activation. The top gene set enriched for the gamma- and titanium-irradiated samples involved KRAS pathway activation and genes activated in TNF-treated cells, respectively. Another difference noted for the high-LET samples was an apparent enrichment in gene sets involved in cycle cycle/mitotic control. It is plausible that the enrichment in these particular pathways results from the complex DNA damage resulting from high-LET exposure where repair processes are not completed during the same time scale as the less complex damage resulting from low-LET radiation.

Analysis of cancer-related lncRNAs using gene ontology and KEGG pathways.

PubMed

Chen, Lei; Zhang, Yu-Hang; Lu, Guohui; Huang, Tao; Cai, Yu-Dong

2017-02-01

Cancer is a disease that involves abnormal cell growth and can invade or metastasize to other tissues. It is known that several factors are related to its initiation, proliferation, and invasiveness. Recently, it has been reported that long non-coding RNAs (lncRNAs) can participate in specific functional pathways and further regulate the biological function of cancer cells. Studies on lncRNAs are therefore helpful for uncovering the underlying mechanisms of cancer biological processes. We investigated cancer-related lncRNAs using gene ontology (GO) terms and KEGG pathway enrichment scores of neighboring genes that are co-expressed with the lncRNAs by extracting important GO terms and KEGG pathways that can help us identify cancer-related lncRNAs. The enrichment theory of GO terms and KEGG pathways was adopted to encode each lncRNA. Then, feature selection methods were employed to analyze these features and obtain the key GO terms and KEGG pathways. The analysis indicated that the extracted GO terms and KEGG pathways are closely related to several cancer associated processes, such as hormone associated pathways, energy associated pathways, and ribosome associated pathways. And they can accurately predict cancer-related lncRNAs. This study provided novel insight of how lncRNAs may affect tumorigenesis and which pathways may play important roles during it. These results could help understanding the biological mechanisms of lncRNAs and treating cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of sediments and organisms in identifying sources of biologically available trace metal contamination

USGS Publications Warehouse

Thomson, E.A.; Luoma, S.N.; Johansson, C.E.; Cain, D.J.

1984-01-01

Sediments and an indicator organism (Macoma balthica, a deposit-feeding bivalve) were used to assess the relative importance of secondary sewage, urban runoff, a landfill containing metal-enriched ash wastes and a yacht harbor in contributing to Ag, Cu and Zn enrichment in South San Francisco Bay. Spatial gradients in sediments and organisms showed Cu and Ag enrichment originated from sewage discharge, whereas Zn enrichment originated from both sewage and urban runoff. Elevated concentrations of Cu in the sediments of the yacht harbor resulted from a high abundance of fine particles. The biological availability of Cu, Ag and Zn did not coincide with metal enrichment in sediments. The availability of Cu and Ag was greatest nearest the sewage outfall and greater in winter and spring than in summer. The availability of Zn in urban runoff appeared to be lower than the availability of Zn associated with sewage.

Biogeochemistry: Hexadecane decay by methanogenesis

USGS Publications Warehouse

Anderson, Robert T.; Lovely, Derek R.

2000-01-01

The potential for the biological conversion of long-chain saturated hydrocarbons to methane under anaerobic conditions has been demonstrated by using an enrichment culture of bacteria to degrade pure-phase hexadecane1. The formation of methane in hydrocarbon-rich subsurface zones could be explained if a similar conversion of long-chain alkanes to methane were to take place in subsurface environments. If this process could be stimulated in the subsurface, it could be used to enhance hydrocarbon recovery from petroleum reserves1, 2. Parkes2, however, questions the environmental significance of the enrichment-culture results1 on the grounds that alkane conversion to methane is very slow and because sulphate-reducing and methanogenic bacteria might both be necessary for even this slow process to occur, restricting the conversion to specialized, unusual zones in sediments. Here we show that, on the contrary, subsurface bacteria can adapt to convert hexadecane to methane rapidly and in the absence of sulphate-reducing bacteria.

The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data.

PubMed

Zhang, Chaoyang; Peng, Li; Zhang, Yaqin; Liu, Zhaoyang; Li, Wenling; Chen, Shilian; Li, Guancheng

2017-06-01

Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched. Cytoscape software was for the construction of protein-protein interaction (PPI) network and module analysis to find the hub genes and key pathways. Finally, weighted correlation network analysis (WGCNA) was conducted to further screen critical gene modules with similar expression pattern and explore their biological significance. Significance analysis identified 1230 DEGs with fold change >2, including 632 significantly down-regulated DEGs and 598 significantly up-regulated DEGs. GO term enrichment analysis suggested that up-regulated DEG significantly enriched in immune response, cell adhesion, cell migration, type I interferon signaling pathway, and cell proliferation, and the down-regulated DEG mainly enriched in response to endoplasmic reticulum stress and endoplasmic reticulum unfolded protein response. KEGG pathway analysis found DEGs significantly enriched in five pathways including complement and coagulation cascades, focal adhesion, ECM-receptor interaction, antigen processing and presentation, and protein processing in endoplasmic reticulum. The top 10 hub genes in HCC were separately GMPS, ACACA, ALB, TGFB1, KRAS, ERBB2, BCL2, EGFR, STAT3, and CD8A, which resulted from PPI network. The top 3 gene interaction modules in PPI network enriched in immune response, organ development, and response to other organism, respectively. WGCNA revealed that the confirmed eight gene modules significantly enriched in monooxygenase and oxidoreductase activity, response to endoplasmic reticulum stress, type I interferon signaling pathway, processing, presentation and binding of peptide antigen, cellular response to cadmium and zinc ion, cell locomotion and differentiation, ribonucleoprotein complex and RNA processing, and immune system process, respectively. In conclusion, we identified some key genes and pathways closely related with HCC initiation and progression by a series of bioinformatics analysis on DEGs. These screened genes and pathways provided for a more detailed molecular mechanism underlying HCC occurrence and progression, holding promise for acting as biomarkers and potential therapeutic targets.

Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice.

PubMed

Smita, Shuchi; Katiyar, Amit; Chinnusamy, Viswanathan; Pandey, Dev M; Bansal, Kailash C

2015-01-01

MYB transcription factor (TF) is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by "top-down" and "guide-gene" approaches. More than 50% of OsMYBs were strongly correlated under 50 experimental conditions with 51 hub genes via "top-down" approach. Further, clusters were identified using Markov Clustering (MCL). To maximize the clustering performance, parameter evaluation of the MCL inflation score (I) was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by "guide-gene" approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought response in rice. Thus, the co-regulatory network analysis facilitated the identification of complex OsMYB regulatory networks, and candidate target regulon genes of selected guide MYB genes. The results contribute to the candidate gene screening, and experimentally testable hypotheses for potential regulatory MYB TFs, and their targets under stress conditions.

Applications of systems approaches in the study of rheumatic diseases.

PubMed

Kim, Ki-Jo; Lee, Saseong; Kim, Wan-Uk

2015-03-01

The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features.

The role of biological uptake in iron and manganese cycling in Lake Baikal

USGS Publications Warehouse

Granina, L.Z.; Callender, E.

2006-01-01

The role of biological uptake in the internal cycling of Fe and Mn in Lake Baikal was quantified. Biological uptake, sedimentation consisting of the biogenic and lithogenic fluxes, and remineralization have been evaluated. The results of calculations show that about 5-10% of Fe and Mn accumulated in the lake are annually taken up by biota. More than 80% of this amount is again recycled after remineralization of biological material. At this, the biogenic fluxes of Fe and Mn are 2-4 times less compared to lithogenic ones. Thus not only is oxidation of Fe and Mn within the water column highly enriched in the oxygen that results in settling of Fe and Mn oxides, but also intensive biological uptake of these elements contributes to their fast removal from internal cycling. However, essential remineralization makes this process of minor importance to Fe and Mn cycling in Lake Baikal. ?? Springer 2006.

Biostatistical analysis of quantitative immunofluorescence microscopy images.

PubMed

Giles, C; Albrecht, M A; Lam, V; Takechi, R; Mamo, J C

2016-12-01

Semiquantitative immunofluorescence microscopy has become a key methodology in biomedical research. Typical statistical workflows are considered in the context of avoiding pseudo-replication and marginalising experimental error. However, immunofluorescence microscopy naturally generates hierarchically structured data that can be leveraged to improve statistical power and enrich biological interpretation. Herein, we describe a robust distribution fitting procedure and compare several statistical tests, outlining their potential advantages/disadvantages in the context of biological interpretation. Further, we describe tractable procedures for power analysis that incorporates the underlying distribution, sample size and number of images captured per sample. The procedures outlined have significant potential for increasing understanding of biological processes and decreasing both ethical and financial burden through experimental optimization. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

An attempt to understand glioma stem cell biology through centrality analysis of a protein interaction network.

PubMed

Mallik, Mrinmay Kumar

2018-02-07

Biological networks can be analyzed using "Centrality Analysis" to identify the more influential nodes and interactions in the network. This study was undertaken to create and visualize a biological network comprising of protein-protein interactions (PPIs) amongst proteins which are preferentially over-expressed in glioma cancer stem cell component (GCSC) of glioblastomas as compared to the glioma non-stem cancer cell (GNSC) component and then to analyze this network through centrality analyses (CA) in order to identify the essential proteins in this network and their interactions. In addition, this study proposes a new centrality analysis method pertaining exclusively to transcription factors (TFs) and interactions amongst them. Moreover the relevant molecular functions, biological processes and biochemical pathways amongst these proteins were sought through enrichment analysis. A protein interaction network was created using a list of proteins which have been shown to be preferentially expressed or over-expressed in GCSCs isolated from glioblastomas as compared to the GNSCs. This list comprising of 38 proteins, created using manual literature mining, was submitted to the Reactome FIViz tool, a web based application integrated into Cytoscape, an open source software platform for visualizing and analyzing molecular interaction networks and biological pathways to produce the network. This network was subjected to centrality analyses utilizing ranked lists of six centrality measures using the FIViz application and (for the first time) a dedicated centrality analysis plug-in ; CytoNCA. The interactions exclusively amongst the transcription factors were nalyzed through a newly proposed centrality analysis method called "Gene Expression Associated Degree Centrality Analysis (GEADCA)". Enrichment analysis was performed using the "network function analysis" tool on Reactome. The CA was able to identify a small set of proteins with consistently high centrality ranks that is indicative of their strong influence in the protein protein interaction network. Similarly the newly proposed GEADCA helped identify the transcription factors with high centrality values indicative of their key roles in transcriptional regulation. The enrichment studies provided a list of molecular functions, biological processes and biochemical pathways associated with the constructed network. The study shows how pathway based databases may be used to create and analyze a relevant protein interaction network in glioma cancer stem cells and identify the essential elements within it to gather insights into the molecular interactions that regulate the properties of glioma stem cells. How these insights may be utilized to help the development of future research towards formulation of new management strategies have been discussed from a theoretical standpoint. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

Genetic Insights Into ADHD Biology.

PubMed

Hayman, Victoria; Fernandez, Thomas V

2018-01-01

ADHD is a neurobiological disorder with a large worldwide prevalence causing significant impairment in children, adolescents, and adults. While there is general agreement about genetic contributions toward the disorder, progress in leveraging genetics to learn more about the biology and risk factors for ADHD has been limited. In this perspective, we identified 105 genes from the literature showing at least nominal statistical significance in association with ADHD. We analyzed these genes for enrichment in biological pathways and in known interacting biological networks. We also analyzed the expression patterns of candidate genes across brain regions and across periods of human development. From our analysis, we identify 14 genes that cluster within an interactive gene network, with enrichment in nitric oxide synthase and alpha-1 adrenergic pathways. Furthermore, these genes show enrichment for expression in the cerebellum during childhood through young adulthood, and in the cortex in adolescence and young adulthood. Gene discovery holds great potential for elucidating the unknown biological underpinnings of ADHD. Genome-wide sequencing efforts are underway and are likely to provide important insights that can be leveraged for new treatments and interventions.

Genomics of Mature and Immature Olfactory Sensory Neurons

PubMed Central

Nickell, Melissa D.; Breheny, Patrick; Stromberg, Arnold J.; McClintock, Timothy S.

2014-01-01

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors, were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes. PMID:22252456

Systemic analysis of genome-wide expression profiles identified potential therapeutic targets of demethylation drugs for glioblastoma.

PubMed

Ning, Tongbo; Cui, Hao; Sun, Feng; Zou, Jidian

2017-09-05

Glioblastoma represents one of the most aggressive malignant brain tumors with high morbidity and motility. Demethylation drugs have been developed for its treatment with little efficacy has been observed. The purpose of this study was to screen therapeutic targets of demethylation drugs or bioactive molecules for glioblastoma through systemic bioinformatics analysis. We firstly downloaded genome-wide expression profiles from the Gene Expression Omnibus (GEO) and conducted the primary analysis through R software, mainly including preprocessing of raw microarray data, transformation between probe ID and gene symbol and identification of differential expression genes (DEGs). Secondly, functional enrichment analysis was conducted via the Database for Annotation, Visualization and Integrated Discovery (DAVID) to explore biological processes involved in the development of glioblastoma. Thirdly, we constructed protein-protein interaction (PPI) network of interested genes and conducted cross analysis for multi datasets to obtain potential therapeutic targets for glioblastoma. Finally, we further confirmed the therapeutic targets through real-time RT-PCR. As a result, biological processes that related to cancer development, amino metabolism, immune response and etc. were found to be significantly enriched in genes that differential expression in glioblastoma and regulated by 5'aza-dC. Besides, network and cross analysis identified ACAT2, UFC1 and CYB5R1 as novel therapeutic targets of demethylation drugs which also confirmed by real time RT-PCR. In conclusions, our study identified several biological processes and genes that involved in the development of glioblastoma and regulated by 5'aza-dC, which would be helpful for the treatment of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

The Gene Ontology of eukaryotic cilia and flagella.

PubMed

Roncaglia, Paola; van Dam, Teunis J P; Christie, Karen R; Nacheva, Lora; Toedt, Grischa; Huynen, Martijn A; Huntley, Rachael P; Gibson, Toby J; Lomax, Jane

2017-01-01

Recent research into ciliary structure and function provides important insights into inherited diseases termed ciliopathies and other cilia-related disorders. This wealth of knowledge needs to be translated into a computational representation to be fully exploitable by the research community. To this end, members of the Gene Ontology (GO) and SYSCILIA Consortia have worked together to improve representation of ciliary substructures and processes in GO. Members of the SYSCILIA and Gene Ontology Consortia suggested additions and changes to GO, to reflect new knowledge in the field. The project initially aimed to improve coverage of ciliary parts, and was then broadened to cilia-related biological processes. Discussions were documented in a public tracker. We engaged the broader cilia community via direct consultation and by referring to the literature. Ontology updates were implemented via ontology editing tools. So far, we have created or modified 127 GO terms representing parts and processes related to eukaryotic cilia/flagella or prokaryotic flagella. A growing number of biological pathways are known to involve cilia, and we continue to incorporate this knowledge in GO. The resulting expansion in GO allows more precise representation of experimentally derived knowledge, and SYSCILIA and GO biocurators have created 199 annotations to 50 human ciliary proteins. The revised ontology was also used to curate mouse proteins in a collaborative project. The revised GO and annotations, used in comparative 'before and after' analyses of representative ciliary datasets, improve enrichment results significantly. Our work has resulted in a broader and deeper coverage of ciliary composition and function. These improvements in ontology and protein annotation will benefit all users of GO enrichment analysis tools, as well as the ciliary research community, in areas ranging from microscopy image annotation to interpretation of high-throughput studies. We welcome feedback to further enhance the representation of cilia biology in GO.

Global pressures, specific responses: effects of nutrient enrichment in streams from different biomes

NASA Astrophysics Data System (ADS)

Artigas, Joan; García-Berthou, Emili; Bauer, Delia E.; Castro, Maria I.; Cochero, Joaquín; Colautti, Darío C.; Cortelezzi, Agustina; Donato, John C.; Elosegi, Arturo; Feijoó, Claudia; Giorgi, Adonis; Gómez, Nora; Leggieri, Leonardo; Muñoz, Isabel; Rodrigues-Capítulo, Alberto; Romaní, Anna M.; Sabater, Sergi

2013-03-01

We assessed the effects of nutrient enrichment on three stream ecosystems running through distinct biomes (Mediterranean, Pampean and Andean). We increased the concentrations of N and P in the stream water 1.6-4-fold following a before-after control-impact paired series (BACIPS) design in each stream, and evaluated changes in the biomass of bacteria, primary producers, invertebrates and fish in the enriched (E) versus control (C) reaches after nutrient addition through a predictive-BACIPS approach. The treatment produced variable biomass responses (2-77% of explained variance) among biological communities and streams. The greatest biomass response was observed for algae in the Andean stream (77% of the variance), although fish also showed important biomass responses (about 9-48%). The strongest biomass response to enrichment (77% in all biological compartments) was found in the Andean stream. The magnitude and seasonality of biomass responses to enrichment were highly site specific, often depending on the basal nutrient concentration and on windows of ecological opportunity (periods when environmental constraints other than nutrients do not limit biomass growth). The Pampean stream, with high basal nutrient concentrations, showed a weak response to enrichment (except for invertebrates), whereas the greater responses of Andean stream communities were presumably favored by wider windows of ecological opportunity in comparison to those from the Mediterranean stream. Despite variation among sites, enrichment globally stimulated the algal-based food webs (algae and invertebrate grazers) but not the detritus-based food webs (bacteria and invertebrate shredders). This study shows that nutrient enrichment tends to globally enhance the biomass of stream biological assemblages, but that its magnitude and extent within the food web are complex and are strongly determined by environmental factors and ecosystem structure.

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

PubMed

O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

2017-04-25

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

Enhanced Dielectrophoretic Enrichment of Nanoparticles Using a Nanostructured Tip for Nanoengineered Medicine and Biology

NASA Astrophysics Data System (ADS)

Yeo, Woonhong

2011-12-01

Enrichment of low-concentration nanoparticles (NPs) is of great interest in the fields of medicine, biology, and environment. In particular, the enrichment of bioparticles such as virus, quantum dots, DNA, or protein can have broad impacts on disease diagnosis, drug discovery, and environmental monitoring. Currently available NP enrichment methods employ centrifugation, microfiltration, or magnetic field. However, these methods are limited in cumbersome preparation steps, low yield, and low throughput. Electric field-based methods have demonstrated potential for NP enrichment, but two-dimensional planar electrodes are limited in sensitivity, molecular transfer, and imaging capability. In addition, the detection of low abundance, non-amplifiable particles such as proteins and metals is very challenging due to the low efficiency of current methods. In this dissertation, the challenges are addressed by nanotip-based NP enrichment. Fundamentals of NP enrichment are studied with a nanostructured tip. The nanotip-based NP enrichment is investigated by correlating a dielectrophoretic (DEP) force with Brownian motion force. In experiment, the predicted NP enrichment is validated by using gold (Au) NPs. The DEP effective distance for NP enrichment with a nanotip is suggested. Sequence-specific enrichment of oligonucleotides is studied by considering DEP force, Brownian motion, and affinity binding. In experiment, the optimal parameters for ultimate enrichment performance are studied using a hybridization assay. In the assay, a nanotip is functionalized with probe-oligonucleotides for sequence-specific binding. Size-specific NP enrichment is explored by studying DEP, capillary action, and viscosity. The capillary action force with a nanotip is calculated analytically, which is then compared with the DEP force. The viscosity effect is considered for NP capturing on a nanotip. The studied size-specific enrichment mechanism is validated in experiment by using various polystyrene nanospheres. The studied enrichment mechanism of NPs with a nanotip is applied to the detection of viral particles. In the characterization study, T7 viral particles having 50 nm in diameter are observed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). In experiment, the viral particles in a buffer are enriched to a nanotip by DEP, and captured onto the nanotip by DEP and viscosity. The captured viral particles on the nanotip are detected by fluorescence microscopy for whole nanotip observation, and validated by SEM. The enhanced DEP enrichment of NPs using a nanotip shows great potential for highly sensitive NP detection and analysis in nanoengineered medicine and biology.

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.

PubMed

Gessner, Denise K; Winkler, Anne; Koch, Christian; Dusel, Georg; Liebisch, Gerhard; Ringseis, Robert; Eder, Klaus

2017-03-23

It was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts, from which 156 were up- and 51 were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation and the most enriched Kyoto Encyclopedia of Genes and Genomes pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that a great part of these genes are involved in endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and inflammatory processes. Accordingly, protein folding, response to unfolded protein, unfolded protein binding, chemokine activity and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins serum amyloid A (SAA) and haptoglobin were reduced in cows fed GSGME compared to control cows. Lipidomic analysis of plasma revealed no differences in the concentrations of individual species of major and minor lipid classes between cows fed GSGME and control cows. Analysis of hepatic transcript profile in cows fed GSGME during the transition period at 1 week postpartum indicates that polyphenol-rich feed components are able to inhibit ER stress-induced UPR and inflammatory processes, both of which are considered to contribute to liver-associated diseases and to impair milk performance in dairy cows, in the liver of dairy cows during early lactation.

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

PubMed

Lu, Zhongyan; Shen, Hong; Shen, Zanming

2018-01-01

In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular immunity, repair, and homeostasis in the rumen epithelium, thereby leading to the switch of concentrate effects from positive to negative with regard to animal production and health. © 2018 The Author(s). Published by S. Karger AG, Basel.

The Effects of Concept Maps on the Academic Success and Attitudes of 11th Graders while Teaching Urinary System

ERIC Educational Resources Information Center

Akay, Sumeyye Ozbey; Kaya, Basturk; Kilic, Selda

2012-01-01

The aim of the present study is to support, enrich, and broaden the process of education using concept maps and to determine the effects of concept maps in biology classes on school success, attitude and retention of the knowledge taught. The present study was conducted as an experimental study with pre-test and post-test control groups. The…

Droplet sorting based on the number of encapsulated particles using a solenoid valve.

PubMed

Cao, Zhenning; Chen, Fangyuan; Bao, Ning; He, Huacheng; Xu, Peisheng; Jana, Saikat; Jung, Sunghwan; Lian, Hongzhen; Lu, Chang

2013-01-07

Droplet microfluidics provides a high-throughput platform for screening subjects and conditions involved in biology. Droplets with encapsulated beads and cells have been increasingly used for studying molecular and cellular biology. Droplet sorting is needed to isolate and analyze the subject of interest during such screening. The vast majority of current sorting techniques use fluorescence intensity emitted by each droplet as the only criterion. However, due to the randomness and imperfections in the encapsulation process, typically a mixed population of droplets with an uneven number of encapsulated particles results and is used for screening. Thus droplet sorting based on the number of encapsulated particles becomes necessary for isolating or enriching droplets with a specific occupancy. In this work, we developed a fluorescence-activated microfluidic droplet sorter that integrated a simple deflection mechanism based on the use of a solenoid valve and a sophisticated signal processing system with a microcontroller as the core. By passing droplets through a narrow interrogation channel, the encapsulated particles were detected individually. The microcontroller conducted the computation to determine the number of encapsulated particles in each droplet and made the sorting decision accordingly that led to actuation of the solenoid valve. We tested both fluorescent beads and stained cells and our results showed high efficiency and accuracy for sorting and enrichment.

Qualitative ubiquitome unveils the potential significances of protein lysine ubiquitination in hyphal growth of Aspergillus nidulans.

PubMed

Chu, Xin-Ling; Feng, Ming-Guang; Ying, Sheng-Hua

2016-02-01

Protein ubiquitination is an evolutionarily conserved post-translational modification process in eukaryotes, and it plays an important role in many biological processes. Aspergillus nidulans, a model filamentous fungus, contributes to our understanding of cellular physiology, metabolism and genetics, but its ubiquitination is not completely revealed. In this study, the ubiquitination sites in the proteome of A. nidulans were identified using a highly sensitive mass spectrometry combined with immuno-affinity enrichment of the ubiquitinated peptides. The 4816 ubiquitination sites were identified in 1913 ubiquitinated proteins, accounting for 18.1% of total proteins in A. nidulans. Bioinformatic analysis suggested that the ubiquitinated proteins associated with a number of biological functions and displayed various sub-cellular localisations. Meanwhile, seven motifs were revealed from the ubiquitinated peptides, and significantly over-presented in the different pathways. Comparison of the enriched functional catalogues indicated that the ubiquitination functions divergently during growth of A. nidulans and Saccharomyces cerevisiae. Additionally, the proteins in A. nidulans-specific sub-category (cell growth/morphogenesis) were subjected to the protein interaction analysis which demonstrated that ubiquitination is involved in the comprehensive protein interactions. This study presents a first proteomic view of ubiquitination in the filamentous fungus, and provides an initial framework for exploring the physiological roles of ubiquitination in A. nidulans.

Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

NASA Astrophysics Data System (ADS)

Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

2017-02-01

The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

Characterizing Cancer Drug Response and Biological Correlates: A Geometric Network Approach.

PubMed

Pouryahya, Maryam; Oh, Jung Hun; Mathews, James C; Deasy, Joseph O; Tannenbaum, Allen R

2018-04-23

In the present work, we apply a geometric network approach to study common biological features of anticancer drug response. We use for this purpose the panel of 60 human cell lines (NCI-60) provided by the National Cancer Institute. Our study suggests that mathematical tools for network-based analysis can provide novel insights into drug response and cancer biology. We adopted a discrete notion of Ricci curvature to measure, via a link between Ricci curvature and network robustness established by the theory of optimal mass transport, the robustness of biological networks constructed with a pre-treatment gene expression dataset and coupled the results with the GI50 response of the cell lines to the drugs. Based on the resulting drug response ranking, we assessed the impact of genes that are likely associated with individual drug response. For genes identified as important, we performed a gene ontology enrichment analysis using a curated bioinformatics database which resulted in biological processes associated with drug response across cell lines and tissue types which are plausible from the point of view of the biological literature. These results demonstrate the potential of using the mathematical network analysis in assessing drug response and in identifying relevant genomic biomarkers and biological processes for precision medicine.

DISCO-SCA and Properly Applied GSVD as Swinging Methods to Find Common and Distinctive Processes

PubMed Central

Van Deun, Katrijn; Van Mechelen, Iven; Thorrez, Lieven; Schouteden, Martijn; De Moor, Bart; van der Werf, Mariët J.; De Lathauwer, Lieven; Smilde, Age K.; Kiers, Henk A. L.

2012-01-01

Background In systems biology it is common to obtain for the same set of biological entities information from multiple sources. Examples include expression data for the same set of orthologous genes screened in different organisms and data on the same set of culture samples obtained with different high-throughput techniques. A major challenge is to find the important biological processes underlying the data and to disentangle therein processes common to all data sources and processes distinctive for a specific source. Recently, two promising simultaneous data integration methods have been proposed to attain this goal, namely generalized singular value decomposition (GSVD) and simultaneous component analysis with rotation to common and distinctive components (DISCO-SCA). Results Both theoretical analyses and applications to biologically relevant data show that: (1) straightforward applications of GSVD yield unsatisfactory results, (2) DISCO-SCA performs well, (3) provided proper pre-processing and algorithmic adaptations, GSVD reaches a performance level similar to that of DISCO-SCA, and (4) DISCO-SCA is directly generalizable to more than two data sources. The biological relevance of DISCO-SCA is illustrated with two applications. First, in a setting of comparative genomics, it is shown that DISCO-SCA recovers a common theme of cell cycle progression and a yeast-specific response to pheromones. The biological annotation was obtained by applying Gene Set Enrichment Analysis in an appropriate way. Second, in an application of DISCO-SCA to metabolomics data for Escherichia coli obtained with two different chemical analysis platforms, it is illustrated that the metabolites involved in some of the biological processes underlying the data are detected by one of the two platforms only; therefore, platforms for microbial metabolomics should be tailored to the biological question. Conclusions Both DISCO-SCA and properly applied GSVD are promising integrative methods for finding common and distinctive processes in multisource data. Open source code for both methods is provided. PMID:22693578

A DUAL PLATFORM FOR SELECTIVE ANALYTE ENRICHMENT AND IONIZATION IN MASS SPECTROMETRY USING APTAMER-CONJUGATED GRAPHENE OXIDE

PubMed Central

Gulbakan, Basri; Yasun, Emir; Shukoor, M. Ibrahim; Zhu, Zhi; You, Mingxu; Tan, Xiaohong; Sanchez, Hernan; Powell, David H.; Dai, Hongjie; Tan, Weihong

2010-01-01

This study demonstrates the use of aptamer-conjugated graphene oxide as an affinity extraction and detection platform for analytes from complex biological media. We have shown that cocaine and adenosine can be selectively enriched from plasma samples and that direct mass spectrometric readout can be obtained without a matrix and with greatly improved signal-to-noise ratios. The aptamer conjugated graphene oxide has clear advantages in target enrichment and in generating highly efficient ionization of target molecules for mass spectrometry. These results demonstrate the utility of the approach for analysis of small molecules in real biological samples. PMID:21090719

clusterProfiler: an R package for comparing biological themes among gene clusters.

PubMed

Yu, Guangchuang; Wang, Li-Gen; Han, Yanyan; He, Qing-Yu

2012-05-01

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.

Inorganic sulfur-nitrogen compounds: from gunpowder chemistry to the forefront of biological signaling.

PubMed

Cortese-Krott, Miriam M; Butler, Anthony R; Woollins, J Derek; Feelisch, Martin

2016-04-14

The reactions between inorganic sulfur and nitrogen-bearing compounds to form S-N containing species have a long history and, besides assuming importance in industrial synthetic processes, are of relevance to microbial metabolism; waste water treatment; aquatic, soil and atmospheric chemistry; and combustion processes. The recent discovery that hydrogen sulfide and nitric oxide exert often similar, sometimes mutually dependent effects in a variety of biological systems, and that the chemical interaction of these two species leads to formation of S-N compounds brought this chemistry to the attention of physiologists, biochemists and physicians. We here provide a perspective about the potential role of S-N compounds in biological signaling and briefly review their chemical properties and bioactivities in the context of the chronology of their discovery. Studies of the biological role of NO revealed why its chemistry is ideally suited for the tasks Nature has chosen for it; realising how the distinctive properties of sulfur can enrich this bioactivity does much to revive 'die Freude am experimentellen Spiel' of the pioneers in this field.

GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis.

PubMed

Zheng, Qi; Wang, Xiu-Jie

2008-07-01

Gene Ontology (GO) analysis has become a commonly used approach for functional studies of large-scale genomic or transcriptomic data. Although there have been a lot of software with GO-related analysis functions, new tools are still needed to meet the requirements for data generated by newly developed technologies or for advanced analysis purpose. Here, we present a Gene Ontology Enrichment Analysis Software Toolkit (GOEAST), an easy-to-use web-based toolkit that identifies statistically overrepresented GO terms within given gene sets. Compared with available GO analysis tools, GOEAST has the following improved features: (i) GOEAST displays enriched GO terms in graphical format according to their relationships in the hierarchical tree of each GO category (biological process, molecular function and cellular component), therefore, provides better understanding of the correlations among enriched GO terms; (ii) GOEAST supports analysis for data from various sources (probe or probe set IDs of Affymetrix, Illumina, Agilent or customized microarrays, as well as different gene identifiers) and multiple species (about 60 prokaryote and eukaryote species); (iii) One unique feature of GOEAST is to allow cross comparison of the GO enrichment status of multiple experiments to identify functional correlations among them. GOEAST also provides rigorous statistical tests to enhance the reliability of analysis results. GOEAST is freely accessible at http://omicslab.genetics.ac.cn/GOEAST/

Controversial Issues within Biology: Enriching Biology Teaching.

ERIC Educational Resources Information Center

Van Rooy, Wilhelmina

2000-01-01

Describes the development and implementation of a senior high school biology lesson concerned with organ transplantation. Discusses the teacher's rationale and techniques for using controversial issues in science teaching. (Contains 18 references.) (Author/WRM)

Outlier analysis of functional genomic profiles enriches for oncology targets and enables precision medicine.

PubMed

Zhu, Zhou; Ihle, Nathan T; Rejto, Paul A; Zarrinkar, Patrick P

2016-06-13

Genome-scale functional genomic screens across large cell line panels provide a rich resource for discovering tumor vulnerabilities that can lead to the next generation of targeted therapies. Their data analysis typically has focused on identifying genes whose knockdown enhances response in various pre-defined genetic contexts, which are limited by biological complexities as well as the incompleteness of our knowledge. We thus introduce a complementary data mining strategy to identify genes with exceptional sensitivity in subsets, or outlier groups, of cell lines, allowing an unbiased analysis without any a priori assumption about the underlying biology of dependency. Genes with outlier features are strongly and specifically enriched with those known to be associated with cancer and relevant biological processes, despite no a priori knowledge being used to drive the analysis. Identification of exceptional responders (outliers) may not lead only to new candidates for therapeutic intervention, but also tumor indications and response biomarkers for companion precision medicine strategies. Several tumor suppressors have an outlier sensitivity pattern, supporting and generalizing the notion that tumor suppressors can play context-dependent oncogenic roles. The novel application of outlier analysis described here demonstrates a systematic and data-driven analytical strategy to decipher large-scale functional genomic data for oncology target and precision medicine discoveries.

Transcriptome-wide discovery of circular RNAs in Archaea

PubMed Central

Danan, Miri; Schwartz, Schraga; Edelheit, Sarit; Sorek, Rotem

2012-01-01

Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms. PMID:22140119

Highly efficient enrichment of low-abundance intact proteins by core-shell structured Fe3O4-chitosan@graphene composites.

PubMed

Zhang, Peng; Fang, Xiaoni; Yan, Guoquan; Gao, Mingxia; Zhang, Xiangmin

2017-11-01

In proteomics research, the screening and monitoring of disease biomarkers is still a major challenge, mainly due to their low concentration in biological samples. However, the universal enrichment of intact proteins has not been further studied. In this work, we developed a Fe 3 O 4 -chitosan@graphene (Fe 3 O 4 -CS@G) core-shell composite to enrich low-abundance proteins from biological samples. Fe 3 O 4 -CS@G composite holds chitosan layer decorated Fe 3 O 4 core, which improves the hydrophilicity of materials greatly. Meanwhile, the graphene nanosheets shell formed via electrostatic assembly endows the composite with huge surface area (178m 2 /g). The good water dispersibility ensures the sufficient contact opportunities between graphene composites and proteins, and the large surface area provides enough adsorption sites for the enrichment of proteins. Using Fe 3 O 4 -CS@G, four standard proteins Cyt-c, BSA, Myo and OVA were enriched with better adsorption capacity and recovery rate, compared with previously reported magnetic graphene composites. Additionally, the mechanism of compared to" is corrected into "compared with". proteins adsorption on Fe 3 O 4 -CS@G was further studied, which indicates that hydrophobic and electrostatic interaction work together to facilitate the universal and efficient enrichment of proteins. Human plasma sample was employed to further evaluate the enrichment performance of Fe 3 O 4 -CS@G. Eventually, 123 proteins were identified from one of SAX fractions of human plasma, which is much better than commercial Sep-pak C18 enrichment column (39 proteins). All these outstanding performances suggest that Fe 3 O 4 -CS@G is an ideal platform for the enrichment of low-abundance intact proteins and thus holds great potential to facilitate the identification of biomarkers from biological samples in proteomics research. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution and characteristic of nitrite-dependent anaerobic methane oxidation bacteria by comparative analysis of wastewater treatment plants and agriculture fields in northern China

PubMed Central

Ma, Ru

2016-01-01

Nitrite-dependent anaerobic methane oxidation (n-damo) is a recently discovered biological process which has been arousing global attention because of its potential in minimizing greenhouse gases emissions. In this study, molecular biological techniques and potential n-damo activity batch experiments were conducted to investigate the presence and diversity of M. oxyfera bacteria in paddy field, corn field, and wastewater treatment plant (WWTP) sites in northern China, as well as lab-scale n-damo enrichment culture. N-damo enrichment culture showed the highest abundance of M. oxyfera bacteria, and positive correlation was observed between potential n-damo rate and abundance of M. oxyfera bacteria. Both paddy field and corn field sites were believed to be better inoculum than WWTP for the enrichment of M. oxyfera bacteria due to their higher abundance and the diversity of M. oxyfera bacteria. Comparative analysis revealed that long biomass retention time, low NH\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${}_{4}^{+}$\\end{document}4+ and high NO\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${}_{2}^{-}$\\end{document}2− content were suitable for the growth of M. oxyfera bacteria. PMID:27994974

Comprehensive Gene expression meta-analysis and integrated bioinformatic approaches reveal shared signatures between thrombosis and myeloproliferative disorders

PubMed Central

Jha, Prabhash Kumar; Vijay, Aatira; Sahu, Anita; Ashraf, Mohammad Zahid

2016-01-01

Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes. Using INMEX bioinformatic tool, based on combined Effect Size (ES) approaches, we identified a total of 1,157 differentially expressed genes (DEGs) (697 overexpressed and 460 underexpressed genes) shared between the three diseases. EnrichR tool’s rich library was used for comprehensive functional enrichment and pathway analysis which revealed “mRNA Splicing” and “SUMO E3 ligases SUMOylate target proteins” among the most enriched terms. Network based meta-analysis identified MYC and FN1 to be the most highly ranked hub genes. Our results reveal that the alterations in biomarkers of the coagulation cascade like F2R, PROS1, SELPLG and ITGB2 were common between the three diseases. Interestingly, the study has generated a novel database of candidate genetic markers, pathways and transcription factors shared between thrombosis and MPDs, which might aid in the development of prognostic therapeutic biomarkers. PMID:27892526

Environmental and Biological Data of the Nutrient Enrichment Effects on Stream Ecosystems Project of the National Water Quality Assessment Program, 2003-04

USGS Publications Warehouse

Brightbill, Robin A.; Munn, Mark D.

2008-01-01

In 2000, the U.S. Environmental Protection Agency began the process of developing regional nutrient criteria for streams and rivers. In response to concerns about nutrients by the U.S. Environmental Protection Agency and others, the U.S. Geological Survey National Water Quality Assessment Program began studying the effects of nutrient enrichment on agricultural stream ecosystems to aid in the understanding of how nutrients affect the biota in agricultural streams. Streams within five study areas were sampled either in 2003 or 2004. These five study areas were located within six NAWQA study units: the combined Apalachicola-Chattahoochee-Flint River Basin (ACFB) and Georgia-Florida Coastal Plain Drainages (GAFL), Central Columbia Plateau?Yakima River Basin (CCYK), Central Nebraska Basins (CNBR), Potomac River?Delmarva Peninsula (PODL), and the White-Miami River Basin (WHMI). Data collected included nutrients (nitrogen and phosphorous) and other chemical parameters, biological samples (chlorophyll, algal assemblages, invertebrate assemblages, and some fish assemblages), stream habitat, and riparian and basin information. This report describes and presents the data collected from these study areas.

Analysis of key microbial community during the start-up of anaerobic ammonium oxidation process with paddy soil as inoculated sludge.

PubMed

Xu, Xianglong; Liu, Guohua; Wang, Yuanyuan; Zhang, Yuankai; Wang, Hao; Qi, Lu; Wang, Hongchen

2018-02-01

A sequencing batch reactor (SBR)-anaerobic ammonium oxidation (anammox) system was started up with the paddy soil as inoculated sludge. The key microbial community structure in the system along with the enrichment time was investigated by using molecular biology methods (e.g., high-throughput 16S rRNA gene sequencing and quantitative PCR). Meanwhile, the influent and effluent water quality was continuously monitored during the whole start-up stage. The results showed that the microbial diversity decreased as the operation time initially and increased afterwards, and the microbial niches in the system were redistributed. The anammox bacterial community structure in the SBR-anammox system shifted during the enrichment, the most dominant anammox bacteria were CandidatusJettenia. The maximum biomass of anammox bacteria achieved 1.68×10 9 copies/g dry sludge during the enrichment period, and the highest removal rate of TN achieved around 75%. Copyright © 2017. Published by Elsevier B.V.

Biological control of aragonite formation in stony corals

NASA Astrophysics Data System (ADS)

Von Euw, Stanislas; Zhang, Qihong; Manichev, Viacheslav; Murali, Nagarajan; Gross, Juliane; Feldman, Leonard C.; Gustafsson, Torgny; Flach, Carol; Mendelsohn, Richard; Falkowski, Paul G.

2017-06-01

Little is known about how stony corals build their calcareous skeletons. There are two prevailing hypotheses: that it is a physicochemically dominated process and that it is a biologically mediated one. Using a combination of ultrahigh-resolution three-dimensional imaging and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy, we show that mineral deposition is biologically driven. Randomly arranged, amorphous nanoparticles are initially deposited in microenvironments enriched in organic material; they then aggregate and form ordered aragonitic structures through crystal growth by particle attachment. Our NMR results are consistent with heterogeneous nucleation of the solid mineral phase driven by coral acid-rich proteins. Such a mechanism suggests that stony corals may be able to sustain calcification even under lower pH conditions that do not favor the inorganic precipitation of aragonite.

Payao: a community platform for SBML pathway model curation

PubMed Central

Matsuoka, Yukiko; Ghosh, Samik; Kikuchi, Norihiro; Kitano, Hiroaki

2010-01-01

Summary: Payao is a community-based, collaborative web service platform for gene-regulatory and biochemical pathway model curation. The system combines Web 2.0 technologies and online model visualization functions to enable a collaborative community to annotate and curate biological models. Payao reads the models in Systems Biology Markup Language format, displays them with CellDesigner, a process diagram editor, which complies with the Systems Biology Graphical Notation, and provides an interface for model enrichment (adding tags and comments to the models) for the access-controlled community members. Availability and implementation: Freely available for model curation service at http://www.payaologue.org. Web site implemented in Seaser Framework 2.0 with S2Flex2, MySQL 5.0 and Tomcat 5.5, with all major browsers supported. Contact: kitano@sbi.jp PMID:20371497

Do Houseflies Think? Patterns of Induction and Biological Beliefs in Development.

ERIC Educational Resources Information Center

Gutheil, Grant; Vera, Alonzo; Keil, Frank C.

1998-01-01

Examined preschoolers' inductive inferences across biological and non-biological kinds. Found support for gradual-enrichment model of conceptual change. Four-year-olds had a limited, coherent, independent biological theory which may form the basis of mature understanding of biological kinds. Explored results in terms of multiple explanatory…

Impact of Long-Term Forest Enrichment Planting on the Biological Status of Soil in a Deforested Dipterocarp Forest in Perak, Malaysia

PubMed Central

Karam, D. S.; Arifin, A.; Radziah, O.; Shamshuddin, J.; Majid, N. M.; Hazandy, A. H.; Zahari, I.; Nor Halizah, A. H.; Rui, T. X.

2012-01-01

Deforestation leads to the deterioration of soil fertility which occurs rapidly under tropical climates. Forest rehabilitation is one of the approaches to restore soil fertility and increase the productivity of degraded areas. The objective of this study was to evaluate and compare soil biological properties under enrichment planting and secondary forests at Tapah Hill Forest Reserve, Perak after 42 years of planting. Both areas were excessively logged in the 1950s and left idle without any appropriate forest management until 1968 when rehabilitation program was initiated. Six subplots (20 m × 20 m) were established within each enrichment planting (F1) and secondary forest (F2) plots, after which soil was sampled at depths of 0–15 cm (topsoil) and 15–30 cm (subsoil). Results showed that total mean microbial enzymatic activity, as well as biomass C and N content, was significantly higher in F1 compared to F2. The results, despite sample variability, suggest that the rehabilitation program improves the soil biological activities where high rate of soil organic matter, organic C, N, suitable soil acidity range, and abundance of forest litter is believed to be the predisposing factor promoting higher population of microbial in F1 as compared to F2. In conclusion total microbial enzymatic activity, biomass C and biomass N evaluation were higher in enrichment planting plot compared to secondary forest. After 42 years of planting, rehabilitation or enrichment planting helps to restore the productivity of planted forest in terms of biological parameters. PMID:22606055

Hybrid coexpression link similarity graph clustering for mining biological modules from multiple gene expression datasets.

PubMed

Salem, Saeed; Ozcaglar, Cagri

2014-01-01

Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways.

ESEA: Discovering the Dysregulated Pathways based on Edge Set Enrichment Analysis

PubMed Central

Han, Junwei; Shi, Xinrui; Zhang, Yunpeng; Xu, Yanjun; Jiang, Ying; Zhang, Chunlong; Feng, Li; Yang, Haixiu; Shang, Desi; Sun, Zeguo; Su, Fei; Li, Chunquan; Li, Xia

2015-01-01

Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway-identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). PMID:26267116

Combining multiple tools outperforms individual methods in gene set enrichment analyses.

PubMed

Alhamdoosh, Monther; Ng, Milica; Wilson, Nicholas J; Sheridan, Julie M; Huynh, Huy; Wilson, Michael J; Ritchie, Matthew E

2017-02-01

Gene set enrichment (GSE) analysis allows researchers to efficiently extract biological insight from long lists of differentially expressed genes by interrogating them at a systems level. In recent years, there has been a proliferation of GSE analysis methods and hence it has become increasingly difficult for researchers to select an optimal GSE tool based on their particular dataset. Moreover, the majority of GSE analysis methods do not allow researchers to simultaneously compare gene set level results between multiple experimental conditions. The ensemble of genes set enrichment analyses (EGSEA) is a method developed for RNA-sequencing data that combines results from twelve algorithms and calculates collective gene set scores to improve the biological relevance of the highest ranked gene sets. EGSEA's gene set database contains around 25 000 gene sets from sixteen collections. It has multiple visualization capabilities that allow researchers to view gene sets at various levels of granularity. EGSEA has been tested on simulated data and on a number of human and mouse datasets and, based on biologists' feedback, consistently outperforms the individual tools that have been combined. Our evaluation demonstrates the superiority of the ensemble approach for GSE analysis, and its utility to effectively and efficiently extrapolate biological functions and potential involvement in disease processes from lists of differentially regulated genes. EGSEA is available as an R package at http://www.bioconductor.org/packages/EGSEA/ . The gene sets collections are available in the R package EGSEAdata from http://www.bioconductor.org/packages/EGSEAdata/ . monther.alhamdoosh@csl.com.au mritchie@wehi.edu.au. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†

PubMed Central

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-01-01

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. PMID:26019233

Proteome Analysis of Human Sebaceous Follicle Infundibula Extracted from Healthy and Acne-Affected Skin

PubMed Central

Bek-Thomsen, Malene; Lomholt, Hans B.; Scavenius, Carsten; Enghild, Jan J.; Brüggemann, Holger

2014-01-01

Acne vulgaris is a very common disease of the pilosebaceous unit of the human skin. The pathological processes of acne are not fully understood. To gain further insight sebaceous follicular casts were extracted from 18 healthy and 20 acne-affected individuals by cyanoacrylate-gel biopsies and further processed for mass spectrometry analysis, aiming at a proteomic analysis of the sebaceous follicular casts. Human as well as bacterial proteins were identified. Human proteins enriched in acne and normal samples were detected, respectively. Normal follicular casts are enriched in proteins such as prohibitins and peroxiredoxins which are involved in the protection from various stresses, including reactive oxygen species. By contrast, follicular casts extracted from acne-affected skin contained proteins involved in inflammation, wound healing and tissue remodeling. Among the most distinguishing proteins were myeloperoxidase, lactotransferrin, neutrophil elastase inhibitor and surprisingly, vimentin. The most significant biological process among all acne-enriched proteins was ‘response to a bacterium’. Identified bacterial proteins were exclusively from Propionibacterium acnes. The most abundant P. acnes proteins were surface-exposed dermatan sulphate adhesins, CAMP factors, and a so far uncharacterized lipase in follicular casts extracted from normal as well as acne-affected skin. This is a first proteomic study that identified human proteins together with proteins of the skin microbiota in sebaceous follicular casts. PMID:25238151

[Possibility of fortifying milk nutrient mixtures for children with lactoglobulin against E. coli and Proteus].

PubMed

Zlatnik, E Iu

1986-01-01

Sweet milk nutrient mixtures, biologically active additives (BAA) and lactic acid ferments, intended for child nutrition, were enriched with the immune preparation lactoglobulin against E. coli and Proteus. Serological and immunochemical investigations of hemagglutinating activity and other characteristics of lactoglobulin in the enriched milk mixtures and BAA evidenced that the preparation retained its full value during the technological process and in the period of storage. No signs of lactoglobulin degradation during the production of a test batch of the milk mixture and BAA were detected, and a high hemagglutinating activity with respect to enteropathogenic E. coli and Proteus was recorded. This permitted the author to recommend the lactoglobulin-enriched sweet mixtures for prevention of acute intestinal infections and dysbacteriosis in young children. The in vitro study of the lactoglobulin interaction with pure cultures of lactobacillus and bifidobacteria showed its inertness to eubacteria. Four strains studied retained their growth and acid-forming properties after combined incubation with lactoglobulin and did not inhibit its activity. A conclusion has been made on the possibility of enrichment of lactic acid products, intended for child nutrition, with lactoglobulin against E. coli and Proteus.

Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.

PubMed

Hu, Yan-Shi; Xin, Juncai; Hu, Ying; Zhang, Lei; Wang, Ju

2017-04-27

Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear. A comprehensive and systematic analysis focusing on the biological function and interactions of these genes in the context of AD will therefore provide valuable insights to understand the molecular features of the disease. In this study, we collected genes potentially associated with AD by screening publications on genetic association studies deposited in PubMed. The major biological themes linked with these genes were then revealed by function and biochemical pathway enrichment analysis, and the relation between the pathways was explored by pathway crosstalk analysis. Furthermore, the network features of these AD-related genes were analyzed in the context of human interactome and an AD-specific network was inferred using the Steiner minimal tree algorithm. We compiled 430 human genes reported to be associated with AD from 823 publications. Biological theme analysis indicated that the biological processes and biochemical pathways related to neurodevelopment, metabolism, cell growth and/or survival, and immunology were enriched in these genes. Pathway crosstalk analysis then revealed that the significantly enriched pathways could be grouped into three interlinked modules-neuronal and metabolic module, cell growth/survival and neuroendocrine pathway module, and immune response-related module-indicating an AD-specific immune-endocrine-neuronal regulatory network. Furthermore, an AD-specific protein network was inferred and novel genes potentially associated with AD were identified. By means of network and pathway-based methodology, we explored the pathogenetic mechanism underlying AD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular mechanism underlying AD. In addition, the framework proposed in this study could be used to investigate the pathological molecular network and genes relevant to other complex diseases or phenotypes.

Advances of lab-on-a-chip in isolation, detection and post-processing of circulating tumour cells.

PubMed

Yu, Ling; Ng, Shu Rui; Xu, Yang; Dong, Hua; Wang, Ying Jun; Li, Chang Ming

2013-08-21

Circulating tumour cells (CTCs) are shed by primary tumours and are found in the peripheral blood of patients with metastatic cancers. Recent studies have shown that the number of CTCs corresponds with disease severity and prognosis. Therefore, detection and further functional analysis of CTCs are important for biomedical science, early diagnosis of cancer metastasis and tracking treatment efficacy in cancer patients, especially in point-of-care applications. Over the last few years, there has been an increasing shift towards not only capturing and detecting these rare cells, but also ensuring their viability for post-processing, such as cell culture and genetic analysis. High throughput lab-on-a-chip (LOC) has been fuelled up to process and analyse heterogeneous real patient samples while gaining profound insights for cancer biology. In this review, we highlight how miniaturisation strategies together with nanotechnologies have been used to advance LOC for capturing, separating, enriching and detecting different CTCs efficiently, while meeting the challenges of cell viability, high throughput multiplex or single-cell detection and post-processing. We begin this survey with an introduction to CTC biology, followed by description of the use of various materials, microstructures and nanostructures for design of LOC to achieve miniaturisation, as well as how various CTC capture or separation strategies can enhance cell capture and enrichment efficiencies, purity and viability. The significant progress of various nanotechnologies-based detection techniques to achieve high sensitivities and low detection limits for viable CTCs and/or to enable CTC post-processing are presented and the fundamental insights are also discussed. Finally, the challenges and perspectives of the technologies are enumerated.

A single preovulatory administration of ulipristal acetate affects the decidualization process of the human endometrium during the receptive period of the menstrual cycle.

PubMed

Lira-Albarrán, Saúl; Durand, Marta; Barrera, David; Vega, Claudia; Becerra, Rocio García; Díaz, Lorenza; García-Quiroz, Janice; Rangel, Claudia; Larrea, Fernando

2018-04-27

In order to get further information on the effects of ulipristal acetate (UPA) upon the process of decidualization of endometrium, a functional analysis of the differentially expressed genes in endometrium (DEG) from UPA treated-versus control-cycles of normal ovulatory women was performed. A list of 1183 endometrial DEG, from a previously published study by our group, was submitted to gene ontology, gene enrichment and ingenuity pathway analyses (IPA). This functional analysis showed that decidualization was a biological process overrepresented. Gene set enrichment analysis identified LIF, PRL, IL15 and STAT3 among the most down-regulated genes within the JAK STAT canonical pathway. IPA showed that decidualization of uterus was a bio-function predicted as inhibited by UPA. The results demonstrated that this selective progesterone receptor modulator, when administered during the periovulatory phase of the menstrual cycle, may affect the molecular mechanisms leading to endometrial decidualization in response to progesterone during the period of maximum embryo receptivity. Copyright © 2018 Elsevier B.V. All rights reserved.

Proteomics Reveals the Molecular Underpinnings of Stronger Learning and Memory in Eastern Compared to Western Bees*

PubMed Central

Meng, Lifeng; Huo, Xinmei; Feng, Mao; Fang, Yu; Han, Bin; Hu, Han; Wu, Fan; Li, Jianke

2018-01-01

The eastern (Apis cerana cerana, Acc) and western (Apis mellifera ligustica, Aml) honeybee are two major honeybee species. Surprisingly, little is known about the fundamental molecular neurobiology of brain suborgans of Acc and Aml. We characterized and compared the proteomes of mushroom bodies (MBs), antennal lobes (ALs) and optical lobes (OLs) in the brain of both species, and biologically validated the functions related to learning and memory. Acc and Aml have evolved similar proteome signatures in MBs and OLs to drive the domain-specific neural activities. In MBs of both species, commonly enriched and enhanced functional groups related to protein metabolism and Ca2+ transport relative to ALs and OLs, suggests that proteins and Ca2+ are vital for consolidating learning and memory via modulation of synaptic structure and signal transduction. Furthermore, in OLs of both species, the mainly enriched ribonucleoside metabolism suggests its vital role as second messenger in promoting phototransduction. Notably, in ALs of both species, distinct proteome settings have shaped to prime olfactory learning and memory. In ALs of Acc, this is supported by the enriched cytoskeleton organization to sustain olfactory signaling through modulation of plasticity in glomeruli and intracellular transport. In ALs of Aml, however, the enriched functional groups implicated in hydrogen ion transport are indicative of their importance in supporting olfactory processes by regulation of synaptic transmission. The biological confirmation of enhanced activities of protein metabolism and signal transduction in ALs and MBs of Acc relative to in Aml demonstrates that a stronger sense of olfactory learning and memory has evolved in Acc. The reported first in-depth proteome data of honeybee brain suborgans provide a novel insight into the molecular basis of neurobiology, and is potentially useful for further neurological studies in honeybees and other insects. PMID:29187519

Stage 4S neuroblastoma tumors show a characteristic DNA methylation portrait

PubMed Central

Decock, Anneleen; Ongenaert, Maté; De Wilde, Bram; Brichard, Bénédicte; Noguera, Rosa; Speleman, Frank; Vandesompele, Jo

2016-01-01

ABSTRACT Stage 4S neuroblastoma (NB) is a special type of NB found in infants with metastases at diagnosis and is associated with an excellent outcome due to its remarkable capacity to undergo spontaneous regression. As genomics have not been able to explain this intriguing clinical presentation, we here aimed at profiling the DNA methylome of stage 4S NB to better understand this phenomenon. To this purpose, differential methylation analyses between International Neuroblastoma Staging System (INSS) stage 4S, stage 4 and stage 1/2 were performed, using methyl-CpG-binding domain (MBD) sequencing data of 14 stage 4S, 14 stage 4, and 13 stage 1/2 primary NB tumors (all MYCN non-amplified in order not to confound results). Stage 4S-specific hyper- and hypomethylated promoters were determined and further characterized for genomic localization and function by cytogenetic band enrichment, gene set enrichment, transcription factor target enrichment and differential RNA expression analyses. We show that specific chromosomal locations are enriched for stage 4S differentially methylated promoters and that stage 4S tumors show characteristic hypermethylation of specific subtelomeric promoters. Furthermore, genes involved in important oncogenic pathways, in neural crest development and differentiation, and in epigenetic processes are differentially methylated and expressed in stage 4S tumors. Based on these findings, we describe new biological mechanisms possibly contributing to the stage 4S-specific tumor biology and spontaneous regression. In conclusion, this study is the first to describe the highly characteristic stage 4S DNA methylome. These findings will open new avenues to further unravel the NB pathology in general and stage 4S disease specifically. PMID:27599161

Stage 4S neuroblastoma tumors show a characteristic DNA methylation portrait.

PubMed

Decock, Anneleen; Ongenaert, Maté; De Wilde, Bram; Brichard, Bénédicte; Noguera, Rosa; Speleman, Frank; Vandesompele, Jo

2016-09-06

Stage 4S neuroblastoma (NB) is a special type of NB found in infants with metastases at diagnosis and is associated with an excellent outcome due to its remarkable capacity to undergo spontaneous regression. As genomics have not been able to explain this intriguing clinical presentation, we here aimed at profiling the DNA methylome of stage 4S NB to better understand this phenomenon. To this purpose, differential methylation analyses between International Neuroblastoma Staging System (INSS) stage 4S, stage 4 and stage 1/2 were performed, using methyl-CpG-binding domain (MBD) sequencing data of 14 stage 4S, 14 stage 4, and 13 stage 1/2 primary NB tumors (all MYCN non-amplified in order not to confound results). Stage 4S-specific hyper- and hypo-methylated promoters were determined and further characterized for genomic localization and function by cytogenetic band enrichment, gene set enrichment, transcription factor target enrichment and differential RNA expression analyses. We show that specific chromosomal locations are enriched for stage 4S differentially methylated promoters and that stage 4S tumors show characteristic hypermethylation of subtelomeres. Furthermore, genes involved in important oncogenic pathways, in neural crest development and differentiation, and in epigenetic processes are differentially methylated and expressed in stage 4S tumors. Based on these findings, we describe new biological mechanisms possibly contributing to the stage 4S-specific tumor biology and spontaneous regression. In conclusion, this study is the first to describe the highly characteristic stage 4S DNA methylome. These findings will open new avenues to further unravel the NB pathology in general and stage 4S disease specifically.

Synchrotron based infrared imaging and spectroscopy via focal plane array on live fibroblasts in D2O enriched medium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quaroni, Luca; Zlateva, Theodora; Sarafimov, Blagoj

2014-03-26

We tested the viability of using synchrotron based infrared imaging to study biochemical processes inside living cells. As a model system, we studied fibroblast cells exposed to a medium highly enriched with D2O. We could show that the experimental technique allows us to reproduce at the cellular level measurements that are normally performed on purified biological molecules. We can obtain information about lipid conformation and distribution, kinetics of hydrogen/deuterium exchange, and the formation of concentration gradients of H and O isotopes in water that are associated with cell metabolism. The implementation of the full field technique in a sequential imagingmore » format gives a description of cellular biochemistry and biophysics that contains both spatial and temporal information.« less

Glycoprotein Enrichment Analytical Techniques: Advantages and Disadvantages.

PubMed

Zhu, R; Zacharias, L; Wooding, K M; Peng, W; Mechref, Y

2017-01-01

Protein glycosylation is one of the most important posttranslational modifications. Numerous biological functions are related to protein glycosylation. However, analytical challenges remain in the glycoprotein analysis. To overcome the challenges associated with glycoprotein analysis, many analytical techniques were developed in recent years. Enrichment methods were used to improve the sensitivity of detection, while HPLC and mass spectrometry methods were developed to facilitate the separation of glycopeptides/proteins and enhance detection, respectively. Fragmentation techniques applied in modern mass spectrometers allow the structural interpretation of glycopeptides/proteins, while automated software tools started replacing manual processing to improve the reliability and throughput of the analysis. In this chapter, the current methodologies of glycoprotein analysis were discussed. Multiple analytical techniques are compared, and advantages and disadvantages of each technique are highlighted. © 2017 Elsevier Inc. All rights reserved.

CHAPTER 7: Glycoprotein Enrichment Analytical Techniques: Advantages and Disadvantages

PubMed Central

Zhu, Rui; Zacharias, Lauren; Wooding, Kerry M.; Peng, Wenjing; Mechref, Yehia

2017-01-01

Protein glycosylation is one of the most important posttranslational modifications. Numerous biological functions are related to protein glycosylation. However, analytical challenges remain in the glycoprotein analysis. To overcome the challenges associated with glycoprotein analysis, many analytical techniques were developed in recent years. Enrichment methods were used to improve the sensitivity of detection while HPLC and mass spectrometry methods were developed to facilitate the separation of glycopeptides/proteins and enhance detection, respectively. Fragmentation techniques applied in modern mass spectrometers allow the structural interpretation of glycopeptides/proteins while automated software tools started replacing manual processing to improve the reliability and throughout of the analysis. In this chapter, the current methodologies of glycoprotein analysis were discussed. Multiple analytical techniques are compared, and advantages and disadvantages of each technique are highlighted. PMID:28109440

Magnetic separation techniques in sample preparation for biological analysis: a review.

PubMed

He, Jincan; Huang, Meiying; Wang, Dongmei; Zhang, Zhuomin; Li, Gongke

2014-12-01

Sample preparation is a fundamental and essential step in almost all the analytical procedures, especially for the analysis of complex samples like biological and environmental samples. In past decades, with advantages of superparamagnetic property, good biocompatibility and high binding capacity, functionalized magnetic materials have been widely applied in various processes of sample preparation for biological analysis. In this paper, the recent advancements of magnetic separation techniques based on magnetic materials in the field of sample preparation for biological analysis were reviewed. The strategy of magnetic separation techniques was summarized. The synthesis, stabilization and bio-functionalization of magnetic nanoparticles were reviewed in detail. Characterization of magnetic materials was also summarized. Moreover, the applications of magnetic separation techniques for the enrichment of protein, nucleic acid, cell, bioactive compound and immobilization of enzyme were described. Finally, the existed problems and possible trends of magnetic separation techniques for biological analysis in the future were proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV’s)

PubMed Central

Marycz, Krzysztof; Marędziak, Monika; Weiss, Christine

2017-01-01

This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR) were applied. The extract of Cladophora glomerata enriched with Cr(III) ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III) induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III) ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses. PMID:29292726

The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV's).

PubMed

Marycz, Krzysztof; Michalak, Izabela; Kocherova, Ievgeniia; Marędziak, Monika; Weiss, Christine

2017-12-08

This study investigated in vitro effects of freshwater alga Cladophora glomerata water extract enriched during a biosorption process in Cr(III) trivalent chromium and chromium picolinate on adipose-derived mesenchymal stromal stem cells (ASCs) and extracellular microvesicles (MVs) in equine metabolic syndrome-affected horses. Chemical characterisation of natural Cladophora glomerata was performed with special emphasis on: vitamin C, vitamin E, total phenols, fatty acids, free and protein-bound amino acids as well as measured Cr in algal biomass. To examine the influence of Cladophora glomerata water extracts, in vitro viability, oxidative stress factor accumulation, apoptosis, inflammatory response, biogenesis of mitochondria, autophagy in ASCs of EMS and secretory activity manifested by MV release were investigated. For this purpose, various methods of molecular biology and microscopic observations (i.e., immunofluorescence staining, SEM, TEM, FIB observations, mRNA and microRNA expression by RT-qPCR) were applied. The extract of Cladophora glomerata enriched with Cr(III) ions reduced apoptosis and inflammation in ASCs of EMS horses through improvement of mitochondrial dynamics, decreasing of PDK4 expression and reduction of endoplastic reticulum stress. Moreover, it was found, that Cladophora glomerata and Cr(III) induce antioxidative protection coming from enhanced SOD activity Therefore, Cladophora glomerata enriched with Cr(III) ions might become an interesting future therapeutic agent in the pharmacological treatment of EMS horses.

Experimental evidence of nitrogen control on pCO(2) in phosphorus-enriched humic and clear coastal lagoon waters.

PubMed

Peixoto, Roberta B; Marotta, Humberto; Enrich-Prast, Alex

2013-01-01

Natural and human-induced controls on carbon dioxide (CO(2)) in tropical waters may be very dynamic (over time and among or within ecosystems) considering the potential role of warmer temperatures intensifying metabolic responses and playing a direct role on the balance between photosynthesis and respiration. The high magnitude of biological processes at low latitudes following eutrophication by nitrogen (N) and phosphorus (P) inputs into coastal lagoons waters may be a relevant component of the carbon cycle, showing controls on partial pressure of CO(2) (pCO(2)) that are still poorly understood. Here we assessed the strength of N control on pCO(2) in P-enriched humic and clear coastal lagoons waters, using four experimental treatments in microcosms: control (no additional nutrients) and three levels of N additions coupled to P enrichments. In humic coastal lagoons waters, a persistent CO(2) supersaturation was reported in controls and all nutrient-enriched treatments, ranging from 24- to 4-fold the atmospheric equilibrium value. However, both humic and clear coastal lagoons waters only showed significant decreases in pCO(2) in relation to the controlled microcosms in the two treatments with higher N addition levels. Additionally, clear coastal lagoons water microcosms showed a shift from CO(2) sources to CO(2) sinks, in relation to the atmosphere. Only in the two more N-enriched treatments did pCO(2) substantially decrease, from 650 µatm in controls and less N-enriched treatments to 10 µatm in more N-enriched microcosms. Humic substrates and N inputs can modulate pCO(2) even in P-enriched coastal lagoons waters, thereby being important drivers on CO(2) outgassing from inland waters.

Experimental evidence of nitrogen control on pCO2 in phosphorus-enriched humic and clear coastal lagoon waters

PubMed Central

Peixoto, Roberta B.; Marotta, Humberto; Enrich-Prast, Alex

2013-01-01

Natural and human-induced controls on carbon dioxide (CO2) in tropical waters may be very dynamic (over time and among or within ecosystems) considering the potential role of warmer temperatures intensifying metabolic responses and playing a direct role on the balance between photosynthesis and respiration. The high magnitude of biological processes at low latitudes following eutrophication by nitrogen (N) and phosphorus (P) inputs into coastal lagoons waters may be a relevant component of the carbon cycle, showing controls on partial pressure of CO2 (pCO2) that are still poorly understood. Here we assessed the strength of N control on pCO2 in P-enriched humic and clear coastal lagoons waters, using four experimental treatments in microcosms: control (no additional nutrients) and three levels of N additions coupled to P enrichments. In humic coastal lagoons waters, a persistent CO2 supersaturation was reported in controls and all nutrient-enriched treatments, ranging from 24- to 4-fold the atmospheric equilibrium value. However, both humic and clear coastal lagoons waters only showed significant decreases in pCO2 in relation to the controlled microcosms in the two treatments with higher N addition levels. Additionally, clear coastal lagoons water microcosms showed a shift from CO2 sources to CO2 sinks, in relation to the atmosphere. Only in the two more N-enriched treatments did pCO2 substantially decrease, from 650 µatm in controls and less N-enriched treatments to 10 µatm in more N-enriched microcosms. Humic substrates and N inputs can modulate pCO2 even in P-enriched coastal lagoons waters, thereby being important drivers on CO2 outgassing from inland waters. PMID:23390422

High-throughput simultaneous determination of plasma water deuterium and 18-oxygen enrichment using a high-temperature conversion elemental analyzer with isotope ratio mass spectrometry.

PubMed

Richelle, M; Darimont, C; Piguet-Welsch, C; Fay, L B

2004-01-01

This paper presents a high-throughput method for the simultaneous determination of deuterium and oxygen-18 (18O) enrichment of water samples isolated from blood. This analytical method enables rapid and simple determination of these enrichments of microgram quantities of water. Water is converted into hydrogen and carbon monoxide gases by the use of a high-temperature conversion elemental analyzer (TC-EA), that are then transferred on-line into the isotope ratio mass spectrometer. Accuracy determined with the standard light Antartic precipitation (SLAP) and Greenland ice sheet precipitation (GISP) is reliable for deuterium and 18O enrichments. The range of linearity is from 0 up to 0.09 atom percent excess (APE, i.e. -78 up to 5725 delta per mil (dpm)) for deuterium enrichment and from 0 up to 0.17 APE (-11 up to 890 dpm) for 18O enrichment. Memory effects do exist but can be avoided by analyzing the biological samples in quintuplet. This method allows the determination of 1440 samples per week, i.e. 288 biological samples per week. Copyright 2004 John Wiley & Sons, Ltd.

Principal Angle Enrichment Analysis (PAEA): Dimensionally Reduced Multivariate Gene Set Enrichment Analysis Tool

PubMed Central

Clark, Neil R.; Szymkiewicz, Maciej; Wang, Zichen; Monteiro, Caroline D.; Jones, Matthew R.; Ma’ayan, Avi

2016-01-01

Gene set analysis of differential expression, which identifies collectively differentially expressed gene sets, has become an important tool for biology. The power of this approach lies in its reduction of the dimensionality of the statistical problem and its incorporation of biological interpretation by construction. Many approaches to gene set analysis have been proposed, but benchmarking their performance in the setting of real biological data is difficult due to the lack of a gold standard. In a previously published work we proposed a geometrical approach to differential expression which performed highly in benchmarking tests and compared well to the most popular methods of differential gene expression. As reported, this approach has a natural extension to gene set analysis which we call Principal Angle Enrichment Analysis (PAEA). PAEA employs dimensionality reduction and a multivariate approach for gene set enrichment analysis. However, the performance of this method has not been assessed nor its implementation as a web-based tool. Here we describe new benchmarking protocols for gene set analysis methods and find that PAEA performs highly. The PAEA method is implemented as a user-friendly web-based tool, which contains 70 gene set libraries and is freely available to the community. PMID:26848405

Principal Angle Enrichment Analysis (PAEA): Dimensionally Reduced Multivariate Gene Set Enrichment Analysis Tool.

PubMed

Clark, Neil R; Szymkiewicz, Maciej; Wang, Zichen; Monteiro, Caroline D; Jones, Matthew R; Ma'ayan, Avi

2015-11-01

Gene set analysis of differential expression, which identifies collectively differentially expressed gene sets, has become an important tool for biology. The power of this approach lies in its reduction of the dimensionality of the statistical problem and its incorporation of biological interpretation by construction. Many approaches to gene set analysis have been proposed, but benchmarking their performance in the setting of real biological data is difficult due to the lack of a gold standard. In a previously published work we proposed a geometrical approach to differential expression which performed highly in benchmarking tests and compared well to the most popular methods of differential gene expression. As reported, this approach has a natural extension to gene set analysis which we call Principal Angle Enrichment Analysis (PAEA). PAEA employs dimensionality reduction and a multivariate approach for gene set enrichment analysis. However, the performance of this method has not been assessed nor its implementation as a web-based tool. Here we describe new benchmarking protocols for gene set analysis methods and find that PAEA performs highly. The PAEA method is implemented as a user-friendly web-based tool, which contains 70 gene set libraries and is freely available to the community.

Pathway Distiller - multisource biological pathway consolidation

PubMed Central

2012-01-01

Background One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. Methods After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. Results We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. Conclusions By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments. PMID:23134636

Pathway Distiller - multisource biological pathway consolidation.

PubMed

Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

2012-01-01

One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments.

Cell-selective metabolic labeling of biomolecules with bioorthogonal functionalities.

PubMed

Xie, Ran; Hong, Senlian; Chen, Xing

2013-10-01

Metabolic labeling of biomolecules with bioorthogonal functionalities enables visualization, enrichment, and analysis of the biomolecules of interest in their physiological environments. This versatile strategy has found utility in probing various classes of biomolecules in a broad range of biological processes. On the other hand, metabolic labeling is nonselective with respect to cell type, which imposes limitations for studies performed in complex biological systems. Herein, we review the recent methodological developments aiming to endow metabolic labeling strategies with cell-type selectivity. The cell-selective metabolic labeling strategies have emerged from protein and glycan labeling. We envision that these strategies can be readily extended to labeling of other classes of biomolecules. Copyright © 2013 Elsevier Ltd. All rights reserved.

FACE: Free-Air CO{sub 2} Enrichment for plant research in the field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendrey, G.R.

1992-08-01

Research programs concerning the effects of Carbon Dioxide(CO){sub 2} on cotton plants are described. Biological responses studied include foliage response to CO{sub 2} fluctuations; yield of cotton exposed to CO{sub 2} enrichment; responses of photosynthesis and stomatal conductance to elevated CO{sub 2} in field-grown cotton; cotton leaf and boll temperatures; root response to CO{sub 2} enrichment; and evaluations of cotton response to CO{sub 2} enrichment with canopy reflectance observations.

FACE: Free-Air CO[sub 2] Enrichment for plant research in the field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendrey, G.R.

1992-08-01

Research programs concerning the effects of Carbon Dioxide(CO)[sub 2] on cotton plants are described. Biological responses studied include foliage response to CO[sub 2] fluctuations; yield of cotton exposed to CO[sub 2] enrichment; responses of photosynthesis and stomatal conductance to elevated CO[sub 2] in field-grown cotton; cotton leaf and boll temperatures; root response to CO[sub 2] enrichment; and evaluations of cotton response to CO[sub 2] enrichment with canopy reflectance observations.

Genetic architecture for susceptibility to gout in the KARE cohort study.

PubMed

Shin, Jimin; Kim, Younyoung; Kong, Minyoung; Lee, Chaeyoung

2012-06-01

This study aimed to identify functional associations of cis-regulatory regions with gout susceptibility using data resulted from a genome-wide association study (GWAS), and to show a genetic architecture for gout with interaction effects among genes within each of the identified functions. The GWAS was conducted with 8314 control subjects and 520 patients with gout in the Korea Association REsource cohort. However, genetic associations with any individual nucleotide variants were not discovered by Bonferroni multiple testing in the GWAS (P>1.42 × 10(-7)). Genomic regions enrichment analysis was employed to identify functional associations of cis-regulatory regions. This analysis revealed several biological processes associated with gout susceptibility, and they were quite different from those with serum uric acid level. Epistasis for susceptibility to gout was estimated using entropy decomposition with selected genes within each biological process identified by the genomic regions enrichment analysis. Some epistases among nucleotide sequence variants for gout susceptibility were found to be larger than their individual effects. This study provided the first evidence that genetic factors for gout susceptibility greatly differed from those for serum uric acid level, which may suggest that research endeavors for identifying genetic factors for gout susceptibility should not be heavily dependent on pathogenesis of uric acid. Interaction effects between genes should be examined to explain a large portion of phenotypic variability for gout susceptibility.

Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.

PubMed

Bobek, Vladimir; Kacprzak, Grzegorz; Rzechonek, Adam; Kolostova, Katarina

2014-05-01

Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients. Patients with diagnosed MPM were enrolled into this study. A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope. The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages

PubMed Central

Krizman, Jennifer; Marian, Viorica; Shook, Anthony; Skoe, Erika; Kraus, Nina

2012-01-01

Bilingualism profoundly affects the brain, yielding functional and structural changes in cortical regions dedicated to language processing and executive function [Crinion J, et al. (2006) Science 312:1537–1540; Kim KHS, et al. (1997) Nature 388:171–174]. Comparatively, musical training, another type of sensory enrichment, translates to expertise in cognitive processing and refined biological processing of sound in both cortical and subcortical structures. Therefore, we asked whether bilingualism can also promote experience-dependent plasticity in subcortical auditory processing. We found that adolescent bilinguals, listening to the speech syllable [da], encoded the stimulus more robustly than age-matched monolinguals. Specifically, bilinguals showed enhanced encoding of the fundamental frequency, a feature known to underlie pitch perception and grouping of auditory objects. This enhancement was associated with executive function advantages. Thus, through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound. This study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. PMID:22547804

Biological control of aragonite formation in stony corals.

PubMed

Von Euw, Stanislas; Zhang, Qihong; Manichev, Viacheslav; Murali, Nagarajan; Gross, Juliane; Feldman, Leonard C; Gustafsson, Torgny; Flach, Carol; Mendelsohn, Richard; Falkowski, Paul G

2017-06-02

Little is known about how stony corals build their calcareous skeletons. There are two prevailing hypotheses: that it is a physicochemically dominated process and that it is a biologically mediated one. Using a combination of ultrahigh-resolution three - dimensional imaging and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy, we show that mineral deposition is biologically driven. Randomly arranged, amorphous nanoparticles are initially deposited in microenvironments enriched in organic material; they then aggregate and form ordered aragonitic structures through crystal growth by particle attachment. Our NMR results are consistent with heterogeneous nucleation of the solid mineral phase driven by coral acid-rich proteins. Such a mechanism suggests that stony corals may be able to sustain calcification even under lower pH conditions that do not favor the inorganic precipitation of aragonite. Copyright © 2017, American Association for the Advancement of Science.

Tissue-Specific Transcriptomic Profiling of Sorghum propinquum using a Rice Genome Array

PubMed Central

Zhang, Ting; Zhao, Xiuqin; Huang, Liyu; Liu, Xiaoyue; Zong, Ying; Zhu, Linghua; Yang, Daichang; Fu, Binying

2013-01-01

Sorghum (Sorghum bicolor) is one of the world's most important cereal crops. S. propinquum is a perennial wild relative of S. bicolor with well-developed rhizomes. Functional genomics analysis of S. propinquum, especially with respect to molecular mechanisms related to rhizome growth and development, can contribute to the development of more sustainable grain, forage, and bioenergy cropping systems. In this study, we used a whole rice genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of S. propinquum with special emphasis on rhizome development. A total of 548 tissue-enriched genes were detected, including 31 and 114 unique genes that were expressed predominantly in the rhizome tips (RT) and internodes (RI), respectively. Further GO analysis indicated that the functions of these tissue-enriched genes corresponded to their characteristic biological processes. A few distinct cis-elements, including ABA-responsive RY repeat CATGCA, sugar-repressive TTATCC, and GA-responsive TAACAA, were found to be prevalent in RT-enriched genes, implying an important role in rhizome growth and development. Comprehensive comparative analysis of these rhizome-enriched genes and rhizome-specific genes previously identified in Oryza longistaminata and S. propinquum indicated that phytohormones, including ABA, GA, and SA, are key regulators of gene expression during rhizome development. Co-localization of rhizome-enriched genes with rhizome-related QTLs in rice and sorghum generated functional candidates for future cloning of genes associated with rhizome growth and development. PMID:23536906

SLEPR: A Sample-Level Enrichment-Based Pathway Ranking Method — Seeking Biological Themes through Pathway-Level Consistency

PubMed Central

Yi, Ming; Stephens, Robert M.

2008-01-01

Analysis of microarray and other high throughput data often involves identification of genes consistently up or down-regulated across samples as the first step in extraction of biological meaning. This gene-level paradigm can be limited as a result of valid sample fluctuations and biological complexities. In this report, we describe a novel method, SLEPR, which eliminates this limitation by relying on pathway-level consistencies. Our method first selects the sample-level differentiated genes from each individual sample, capturing genes missed by other analysis methods, ascertains the enrichment levels of associated pathways from each of those lists, and then ranks annotated pathways based on the consistency of enrichment levels of individual samples from both sample classes. As a proof of concept, we have used this method to analyze three public microarray datasets with a direct comparison with the GSEA method, one of the most popular pathway-level analysis methods in the field. We found that our method was able to reproduce the earlier observations with significant improvements in depth of coverage for validated or expected biological themes, but also produced additional insights that make biological sense. This new method extends existing analyses approaches and facilitates integration of different types of HTP data. PMID:18818771

Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer.

PubMed

Xu, Tong-Peng; Wang, Wen-Yu; Ma, Pei; Shuai, You; Zhao, Kun; Wang, Yan-Fen; Li, Wei; Xia, Rui; Chen, Wen-Ming; Zhang, Er-Bao; Shu, Yong-Qian

2018-05-23

Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression. Loss of FOXD2-AS1 function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1 expression promoted cancer progression. The enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins were found to serve as binding partners of FOXD2-AS1 and mediators of FOXD2-AS1 function. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis.

Comprehensive analysis of genetic variations in strictly-defined Leber congenital amaurosis with whole-exome sequencing in Chinese.

PubMed

Wang, Shi-Yuan; Zhang, Qi; Zhang, Xiang; Zhao, Pei-Quan

2016-01-01

To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis (LCA) in Chinese. LCA subjects and their families were retrospectively collected from 2013 to 2015. Firstly, whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found, and then homozygous sites was selected, candidate sites were annotated, and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant (SIFT), Polyphen-2, Mutation assessor, Condel, and Functional Analysis through Hidden Markov Models (FATHMM). Furthermore, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test. Sanger sequencing was used to validate single-nucleotide variations (SNVs). Expanded verification was performed in the rest patients. Totally 51 LCA families with 53 patients and 24 family members were recruited. A total of 104 SNVs (66 LCA-related genes and 15 co-segregated genes) were submitted for expand verification. The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families. Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion, biological adhesion, retinoid metabolic process, and eye development biological adhesion. Additionally, WFS1 and STAU2 had the highest homozygous frequencies. LCA is a highly heterogeneous disease. Mutations in KRT12, CYP1A1, WFS1, and STAU2 may be involved in the development of LCA.

Functional Genomics Assistant (FUGA): a toolbox for the analysis of complex biological networks

PubMed Central

2011-01-01

Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA) - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga. PMID:22035155

The dynamics of food chains under climate change and nutrient enrichment.

PubMed

Binzer, Amrei; Guill, Christian; Brose, Ulrich; Rall, Björn C

2012-11-05

Warming has profound effects on biological rates such as metabolism, growth, feeding and death of organisms, eventually affecting their ability to survive. Using a nonlinear bioenergetic population-dynamic model that accounts for temperature and body-mass dependencies of biological rates, we analysed the individual and interactive effects of increasing temperature and nutrient enrichment on the dynamics of a three-species food chain. At low temperatures, warming counteracts the destabilizing effects of enrichment by both bottom-up (via the carrying capacity) and top-down (via biological rates) mechanisms. Together with increasing consumer body masses, warming increases the system tolerance to fertilization. Simultaneously, warming increases the risk of starvation for large species in low-fertility systems. This effect can be counteracted by increased fertilization. In combination, therefore, two main drivers of global change and biodiversity loss can have positive and negative effects on food chain stability. Our model incorporates the most recent empirical data and may thus be used as the basis for more complex forecasting models incorporating food-web structure.

A Computational Workflow for the Automated Generation of Models of Genetic Designs.

PubMed

Misirli, Göksel; Nguyen, Tramy; McLaughlin, James Alastair; Vaidyanathan, Prashant; Jones, Timothy S; Densmore, Douglas; Myers, Chris; Wipat, Anil

2018-06-05

Computational models are essential to engineer predictable biological systems and to scale up this process for complex systems. Computational modeling often requires expert knowledge and data to build models. Clearly, manual creation of models is not scalable for large designs. Despite several automated model construction approaches, computational methodologies to bridge knowledge in design repositories and the process of creating computational models have still not been established. This paper describes a workflow for automatic generation of computational models of genetic circuits from data stored in design repositories using existing standards. This workflow leverages the software tool SBOLDesigner to build structural models that are then enriched by the Virtual Parts Repository API using Systems Biology Open Language (SBOL) data fetched from the SynBioHub design repository. The iBioSim software tool is then utilized to convert this SBOL description into a computational model encoded using the Systems Biology Markup Language (SBML). Finally, this SBML model can be simulated using a variety of methods. This workflow provides synthetic biologists with easy to use tools to create predictable biological systems, hiding away the complexity of building computational models. This approach can further be incorporated into other computational workflows for design automation.

[Construction of research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier].

PubMed

Sun, E; Xu, Feng-Juan; Zhang, Zhen-Hai; Wei, Ying-Jie; Tan, Xiao-Bin; Cheng, Xu-Dong; Jia, Xiao-Bin

2014-02-01

Based on practice of Epimedium processing mechanism for many years and integrated multidisciplinary theory and technology, this paper initially constructs the research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier, which to form an innovative research mode of the " chemical composition changes-biological transformation-metabolism in vitro and in vivo-intestinal absorption-pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined with specific examples of Epimedium and other Chinese herbal medicine processing mechanism, this paper also discusses the academic thoughts, research methods and key technologies of this research system, which will be conducive to systematically reveal the modem scientific connotation of traditional Chinese medicine processing, and enrich the theory of Chinese herbal medicine processing.

Evaluation of a combined macrophyte-epiphyte bioassay for assessing nutrient enrichment in the Portneuf River, Idaho, USA.

PubMed

Ray, Andrew M; Mebane, Christopher A; Raben, Flint; Irvine, Kathryn M; Marcarelli, Amy M

2014-07-01

We describe and evaluate a laboratory bioassay that uses Lemna minor L. and attached epiphytes to characterize the status of ambient and nutrient-enriched water from the Portneuf River, Idaho. Specifically, we measured morphological (number of fronds, longest surface axis, and root length) and population-level (number of plants and dry mass) responses of L. minor and community-level (ash-free dry mass [AFDM] and chlorophyll a [Chl a]) responses of epiphytes to nutrient enrichment. Overall, measures of macrophyte biomass and abundance increased with increasing concentrations of dissolved phosphorus (P) and responded more predictably to nutrient enrichment than morphological measures. Epiphyte AFDM and Chl a were also greatest in P-enriched water; enrichments of N alone produced no measurable epiphytic response. The epiphyte biomass response did not directly mirror macrophyte biomass responses, illustrating the value of a combined macrophyte-epiphyte assay to more fully evaluate nutrient management strategies. Finally, the most P-enriched waters not only supported greater standing stocks of macrophyte and epiphytes but also had significantly higher water column dissolved oxygen and dissolved organic carbon concentrations and a lower pH. Advantages of this macrophyte-epiphyte bioassay over more traditional single-species assays include the use of a more realistic level of biological organization, a relatively short assay schedule (~10 days), and the inclusion of multiple biological response and water-quality measures.

Evaluation of a combined macrophyte–epiphyte bioassay for assessing nutrient enrichment in the Portneuf River, Idaho, USA

USGS Publications Warehouse

Ray, Andrew M.; Mebane, Christopher A.; Raben, Flint; Irvine, Kathryn M.; Marcarelli, Amy M.

2014-01-01

We describe and evaluate a laboratory bioassay that uses Lemna minor L. and attached epiphytes to characterize the status of ambient and nutrient-enriched water from the Portneuf River, Idaho. Specifically, we measured morphological (number of fronds, longest surface axis, and root length) and population-level (number of plants and dry mass) responses of L. minor and community-level (ash-free dry mass [AFDM] and chlorophyll a [Chl a]) responses of epiphytes to nutrient enrichment. Overall, measures of macrophyte biomass and abundance increased with increasing concentrations of dissolved phosphorus (P) and responded more predictably to nutrient enrichment than morphological measures. Epiphyte AFDM and Chl a were also greatest in P-enriched water; enrichments of N alone produced no measurable epiphytic response. The epiphyte biomass response did not directly mirror macrophyte biomass responses, illustrating the value of a combined macrophyte–epiphyte assay to more fully evaluate nutrient management strategies. Finally, the most P-enriched waters not only supported greater standing stocks of macrophyte and epiphytes but also had significantly higher water column dissolved oxygen and dissolved organic carbon concentrations and a lower pH. Advantages of this macrophyte–epiphyte bioassay over more traditional single-species assays include the use of a more realistic level of biological organization, a relatively short assay schedule (~10 days), and the inclusion of multiple biological response and water-quality measures.

Changes in optical characteristics of surface microlayers in the Peruvian upwelling region hint to photochemically and microbially-mediated DOM turnover

NASA Astrophysics Data System (ADS)

Engel, A.; Galgani, L.

2016-02-01

The coastal upwelling system off Peru is characterized by high biological activity and associated subsurface oxygen minimum zone, leading to an enhanced emission of atmospheric trace gases. High biological productivity in the water column may promote the establishment of enriched organic surface films, key environments for processes regulating gas fluxes across the water-air interface. During M91 cruise to the Peruvian upwelling, we focused our attention on the composition of the sea-surface microlayer (SML), the oceanic uppermost boundary directly subject to high solar radiation, often enriched in specific organic compounds of biological origin like Chromophoric Dissolved Organic Matter (CDOM) and marine gels. In the SML, the continuous photochemical and microbial recycling of organic matter may strongly influence gas exchange between marine systems and the atmosphere. In order to understand organic matter cycling in surface films, we analyzed SML and underlying water samples in 38 stations determining DOC concentrations, amino acids composition, marine gels, CDOM and bacterial abundance as indicators of photochemical and microbial alteration processes. CDOM composition was characterized by spectral slopes (S) values and Excitation-Emission Matrix fluorescence (EEMs), which allow to track changes in molecular weight (MW) of DOM, and to determine potential DOM sources. Profound changes in spectral slope properties were observed suggesting smaller MW CDOM in the SML compared to underlying water. Microbial and photochemical degradation are likely the main drivers for organic matter cycling in the top layer of the ocean. Consequences on the formation of inorganic and organic species highly relevant for air-sea gas exchange and for climate dynamics will be discussed.

FUSE: a profit maximization approach for functional summarization of biological networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

2012-03-21

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states.

PubMed

Li, Wei Vivian; Razaee, Zahra S; Li, Jingyi Jessica

2016-01-11

The dynamics of epigenomic marks in their relevant chromatin states regulate distinct gene expression patterns, biological functions and phenotypic variations in biological processes. The availability of high-throughput epigenomic data generated by next-generation sequencing technologies allows a data-driven approach to evaluate the similarities and differences of diverse tissue and cell types in terms of epigenomic features. While ChromImpute has allowed for the imputation of large-scale epigenomic information to yield more robust data to capture meaningful relationships between biological samples, widely used methods such as hierarchical clustering and correlation analysis cannot adequately utilize epigenomic data to accurately reveal the distinction and grouping of different tissue and cell types. We utilize a three-step testing procedure-ANOVA, t test and overlap test to identify tissue/cell-type- associated enhancers and promoters and to calculate a newly defined Epigenomic Overlap Measure (EPOM). EPOM results in a clear correspondence map of biological samples from different tissue and cell types through comparison of epigenomic marks evaluated in their relevant chromatin states. Correspondence maps by EPOM show strong capability in distinguishing and grouping different tissue and cell types and reveal biologically meaningful similarities between Heart and Muscle, Blood & T-cell and HSC & B-cell, Brain and Neurosphere, etc. The gene ontology enrichment analysis both supports and explains the discoveries made by EPOM and suggests that the associated enhancers and promoters demonstrate distinguishable functions across tissue and cell types. Moreover, the tissue/cell-type-associated enhancers and promoters show enrichment in the disease-related SNPs that are also associated with the corresponding tissue or cell types. This agreement suggests the potential of identifying causal genetic variants relevant to cell-type-specific diseases from our identified associated enhancers and promoters. The proposed EPOM measure demonstrates superior capability in grouping and finding a clear correspondence map of biological samples from different tissue and cell types. The identified associated enhancers and promoters provide a comprehensive catalog to study distinct biological processes and disease variants in different tissue and cell types. Our results also find that the associated promoters exhibit more cell-type-specific functions than the associated enhancers do, suggesting that the non-associated promoters have more housekeeping functions than the non-associated enhancers.

Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with Fe3O4 nanocrystals for highly efficient capture and isotope labeling of phosphopeptides

NASA Astrophysics Data System (ADS)

Chen, Xueqin; Li, Siyuan; Zhang, Xiaoxia; Min, Qianhao; Zhu, Jun-Jie

2015-03-01

Qualitative and quantitative characterization of phosphopeptides by means of mass spectrometry (MS) is the main goal of MS-based phosphoproteomics, but suffers from their low abundance in the large haystack of various biological molecules. Herein, we introduce two-dimensional (2D) metal oxides to tackle this biological separation issue. A nanocomposite composed of titanoniobate nanosheets embedded with Fe3O4 nanocrystals (Fe3O4-TiNbNS) is constructed via a facile cation-exchange approach, and adopted for the capture and isotope labeling of phosphopeptides. In this nanoarchitecture, the 2D titanoniobate nanosheets offer enlarged surface area and a spacious microenvironment for capturing phosphopeptides, while the Fe3O4 nanocrystals not only incorporate a magnetic response into the composite but, more importantly, also disrupt the restacking process between the titanoniobate nanosheets and thus preserve a greater specific surface for binding phosphopeptides. Owing to the extended active surface, abundant Lewis acid sites and excellent magnetic controllability, Fe3O4-TiNbNS demonstrates superior sensitivity, selectivity and capacity over homogeneous bulk metal oxides, layered oxides, and even restacked nanosheets in phosphopeptide enrichment, and further allows in situ isotope labeling to quantify aberrantly-regulated phosphopeptides from sera of leukemia patients. This composite nanosheet greatly contributes to the MS analysis of phosphopeptides and gives inspiration in the pursuit of 2D structured materials for separation of other biological molecules of interests.Qualitative and quantitative characterization of phosphopeptides by means of mass spectrometry (MS) is the main goal of MS-based phosphoproteomics, but suffers from their low abundance in the large haystack of various biological molecules. Herein, we introduce two-dimensional (2D) metal oxides to tackle this biological separation issue. A nanocomposite composed of titanoniobate nanosheets embedded with Fe3O4 nanocrystals (Fe3O4-TiNbNS) is constructed via a facile cation-exchange approach, and adopted for the capture and isotope labeling of phosphopeptides. In this nanoarchitecture, the 2D titanoniobate nanosheets offer enlarged surface area and a spacious microenvironment for capturing phosphopeptides, while the Fe3O4 nanocrystals not only incorporate a magnetic response into the composite but, more importantly, also disrupt the restacking process between the titanoniobate nanosheets and thus preserve a greater specific surface for binding phosphopeptides. Owing to the extended active surface, abundant Lewis acid sites and excellent magnetic controllability, Fe3O4-TiNbNS demonstrates superior sensitivity, selectivity and capacity over homogeneous bulk metal oxides, layered oxides, and even restacked nanosheets in phosphopeptide enrichment, and further allows in situ isotope labeling to quantify aberrantly-regulated phosphopeptides from sera of leukemia patients. This composite nanosheet greatly contributes to the MS analysis of phosphopeptides and gives inspiration in the pursuit of 2D structured materials for separation of other biological molecules of interests. Electronic supplementary information (ESI) available: Sequence of phosphopeptides from the digests of α- and β-casein percentages of the 4 methylated products from peptide β1 at different labeling reaction times; sequence of serum phosphopeptides; XPS spectra of Nb 3d and Ti 2p in layered oxides and H+-stacked nanosheets; phosphopeptide enrichment sensitivity of bulk oxides, layered oxides and H+-stacked nanosheets; AFM image of TiNbNS; saturated adsorption isotherm for pNPP adsorbed on bulk oxides, layered oxides and H+-stacked nanosheets; XPS spectra of Fe3O4-TiNbNS nitrogen adsorption-desorption isotherms and pore size distribution curves for the Fe3O4 nanocrystals; phosphopeptide enrichment sensitivity, capacity and selectivity of the Fe3O4-TiNbNS composites; MS/MS spectra of phosphopeptides enriched from serum; linear relationship between the logarithms of peak area ratio and loading volume ratio. See DOI: 10.1039/c4nr07041k

Dynamic transcription profiles of “Qinguan” apple (Malus × domestica) leaves in response to Marssonina coronaria inoculation

PubMed Central

Xu, Jianhua; Li, Miaomiao; Jiao, Peng; Tao, Hongxia; Wei, Ningning; Ma, Fengwang; Zhang, Junke

2015-01-01

Marssonina apple blotch, caused by the fungus Marssonina coronaria, is one of the most destructive apple diseases in China and East Asia. A better understanding of the plant's response to fungi during pathogenesis is urgently needed to improve plant resistance and to breed resistant cultivars. To address this, the transcriptomes of “Qinguan” (a cultivar with high resistance to M. coronaria) apple leaves were sequenced at 12, 24, 48, and 72 h post-inoculation (hpi) with Marssonina coronaria. The comparative results showed that a total of 1956 genes were differentially expressed between the inoculated and control samples at the 4 time points. Gene ontology (GO) term enrichment analysis of differentially expressed genes (DEGs) revealed changes in cellular component, secondary metabolism including chalcone isomerase activity, phytoalexin biosynthetic process, anthocyanin-containing compound biosynthetic process, lignin biosynthetic process, positive regulation of flavonoid biosynthetic process; and molecular functions or biological processes related to the defense response, biotic stimulus response, wounding response and fungus response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were significantly enriched in flavonoid biosynthesis, vitamin B6 metabolism, phenylpropanoid biosynthesis, and the stilbenoid, diarylheptanoid and gingerol biosynthesis pathways. Furthermore, the importance of changes in cellular components and partial polyphenol compounds when encountering M. coronaria are discussed. PMID:26528306

GeneSCF: a real-time based functional enrichment tool with support for multiple organisms.

PubMed

Subhash, Santhilal; Kanduri, Chandrasekhar

2016-09-13

High-throughput technologies such as ChIP-sequencing, RNA-sequencing, DNA sequencing and quantitative metabolomics generate a huge volume of data. Researchers often rely on functional enrichment tools to interpret the biological significance of the affected genes from these high-throughput studies. However, currently available functional enrichment tools need to be updated frequently to adapt to new entries from the functional database repositories. Hence there is a need for a simplified tool that can perform functional enrichment analysis by using updated information directly from the source databases such as KEGG, Reactome or Gene Ontology etc. In this study, we focused on designing a command-line tool called GeneSCF (Gene Set Clustering based on Functional annotations), that can predict the functionally relevant biological information for a set of genes in a real-time updated manner. It is designed to handle information from more than 4000 organisms from freely available prominent functional databases like KEGG, Reactome and Gene Ontology. We successfully employed our tool on two of published datasets to predict the biologically relevant functional information. The core features of this tool were tested on Linux machines without the need for installation of more dependencies. GeneSCF is more reliable compared to other enrichment tools because of its ability to use reference functional databases in real-time to perform enrichment analysis. It is an easy-to-integrate tool with other pipelines available for downstream analysis of high-throughput data. More importantly, GeneSCF can run multiple gene lists simultaneously on different organisms thereby saving time for the users. Since the tool is designed to be ready-to-use, there is no need for any complex compilation and installation procedures.

Exposure to Nickel, Chromium, or Cadmium Causes Distinct Changes in the Gene Expression Patterns of a Rat Liver Derived Cell Line

DTIC Science & Technology

2011-11-16

nickel, cadmium, and chromium are toxic industrial chemicals with an exposure. While these substances are known to produce adverse health effects leading...in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects...that particular bin. A chi-squared test was used to test bin enrichment ( p ≤0.05). Probe sets that did not contain any biological process annotation were

A Rapid Spin Column-Based Method to Enrich Pathogen Transcripts from Eukaryotic Host Cells Prior to Sequencing

DOE PAGES

Bent, Zachary W.; Poorey, Kunal; LaBauve, Annette E.; ...

2016-12-21

When analyzing pathogen transcriptomes during the infection of host cells, the signal-to-background (pathogen-to-host) ratio of nucleic acids (NA) in infected samples is very small. Despite the advancements in next-generation sequencing, the minute amount of pathogen NA makes standard RNA-seq library preps inadequate for effective gene-level analysis of the pathogen in cases with low bacterial loads. In order to provide a more complete picture of the pathogen transcriptome during an infection, we developed a novel pathogen enrichment technique, which can enrich for transcripts from any cultivable bacteria or virus, using common, readily available laboratory equipment and reagents. To evenly enrich formore » pathogen transcripts, we generate biotinylated pathogen-targeted capture probes in an enzymatic process using the entire genome of the pathogen as a template. The capture probes are hybridized to a strand-specific cDNA library generated from an RNA sample. The biotinylated probes are captured on a monomeric avidin resin in a miniature spin column, and enriched pathogen-specific cDNA is eluted following a series of washes. To test this method, we performed an in vitro time-course infection using Klebsiella pneumoniae to infect murine macrophage cells. K. pneumoniae transcript enrichment efficiency was evaluated using RNA-seq. Bacterial transcripts were enriched up to ~400-fold, and allowed the recovery of transcripts from ~2000–3600 genes not observed in untreated control samples. These additional transcripts revealed interesting aspects of K. pneumoniae biology including the expression of putative virulence factors and the expression of several genes responsible for antibiotic resistance even in the absence of drugs.« less

Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages.

PubMed

Zhan, Siyuan; Zhao, Wei; Song, Tianzeng; Dong, Yao; Guo, Jiazhong; Cao, Jiaxue; Zhong, Tao; Wang, Linjie; Li, Li; Zhang, Hongping

2018-01-01

Muscle growth and development from fetal to neonatal stages consist of a series of delicately regulated and orchestrated changes in expression of genes. In this study, we performed whole transcriptome profiling based on RNA-Seq of caprine longissimus dorsi muscle tissue obtained from prenatal stages (days 45, 60, and 105 of gestation) and neonatal stage (the 3-day-old newborn) to identify genes that are differentially expressed and investigate their temporal expression profiles. A total of 3276 differentially expressed genes (DEGs) were identified (Q value < 0.01). Time-series expression profile clustering analysis indicated that DEGs were significantly clustered into eight clusters which can be divided into two classes (Q value < 0.05), class I profiles with downregulated patterns and class II profiles with upregulated patterns. Based on cluster analysis, GO enrichment analysis found that 75, 25, and 8 terms to be significantly enriched in biological process (BP), cellular component (CC), and molecular function (MF) categories in class I profiles, while 35, 21, and 8 terms to be significantly enriched in BP, CC, and MF in class II profiles. KEGG pathway analysis revealed that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway. DEGs from class II profiles were significantly enriched in 17 pathways and the mainly enriched pathway was AMPK signaling pathway. Finally, six selected DEGs from our sequencing results were confirmed by qPCR. Our study provides a comprehensive understanding of the molecular mechanisms during goat skeletal muscle development from fetal to neonatal stages and valuable information for future studies of muscle development in goats.

A Rapid Spin Column-Based Method to Enrich Pathogen Transcripts from Eukaryotic Host Cells Prior to Sequencing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bent, Zachary W.; Poorey, Kunal; LaBauve, Annette E.

When analyzing pathogen transcriptomes during the infection of host cells, the signal-to-background (pathogen-to-host) ratio of nucleic acids (NA) in infected samples is very small. Despite the advancements in next-generation sequencing, the minute amount of pathogen NA makes standard RNA-seq library preps inadequate for effective gene-level analysis of the pathogen in cases with low bacterial loads. In order to provide a more complete picture of the pathogen transcriptome during an infection, we developed a novel pathogen enrichment technique, which can enrich for transcripts from any cultivable bacteria or virus, using common, readily available laboratory equipment and reagents. To evenly enrich formore » pathogen transcripts, we generate biotinylated pathogen-targeted capture probes in an enzymatic process using the entire genome of the pathogen as a template. The capture probes are hybridized to a strand-specific cDNA library generated from an RNA sample. The biotinylated probes are captured on a monomeric avidin resin in a miniature spin column, and enriched pathogen-specific cDNA is eluted following a series of washes. To test this method, we performed an in vitro time-course infection using Klebsiella pneumoniae to infect murine macrophage cells. K. pneumoniae transcript enrichment efficiency was evaluated using RNA-seq. Bacterial transcripts were enriched up to ~400-fold, and allowed the recovery of transcripts from ~2000–3600 genes not observed in untreated control samples. These additional transcripts revealed interesting aspects of K. pneumoniae biology including the expression of putative virulence factors and the expression of several genes responsible for antibiotic resistance even in the absence of drugs.« less

Biophysical implications of sphingosine accumulation in membrane properties at neutral and acidic pH.

PubMed

Zupancic, Eva; Carreira, Ana C; de Almeida, Rodrigo F M; Silva, Liana C

2014-05-08

Sphingosine (Sph) is a simple lipid involved in the regulation of several biological processes. When accumulated in the late endosomal/lysosomal compartments, Sph causes changes in ion signaling and membrane trafficking, leading to the development of Niemann-Pick disease type C. Little is known about Sph interaction with other lipids in biological membranes; however, understanding the effect of Sph in the physical state of membranes might provide insights into its mode of action. Using complementary established fluorescence approaches, we show that Sph accumulation leads to the formation of Sph-enriched gel domains in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and POPC/sphingomyelin (SM)/cholesterol (Chol) model membranes. These domains are more easily formed in membrane models mimicking the neutral pH plasma membrane environment (PM) as compared to the acidic lysosomal membrane environment (LM), where higher Sph concentrations (or lower temperatures) are required. Electrophoretic light scattering measurements further revealed that in PM-raft models (POPC/SM/Chol), Sph is mainly neutral, whereas in LM models, the positive charge of Sph leads to electrostatic repulsion, reducing the Sph ability to form gel domains. Thus, formation of Sph-enriched domains in cellular membranes might be strongly regulated by Sph charge.

[Exploration of common biological pathways for attention deficit hyperactivity disorder and low birth weight].

PubMed

Xiang, Bo; Yu, Minglan; Liang, Xuemei; Lei, Wei; Huang, Chaohua; Chen, Jing; He, Wenying; Zhang, Tao; Li, Tao; Liu, Kezhi

2017-12-10

To explore common biological pathways for attention deficit hyperactivity disorder (ADHD) and low birth weight (LBW). Thei-Gsea4GwasV2 software was used to analyze the result of genome-wide association analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally significant (P< 0.05, FDR< 0.25) pathways were tested for replication in ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to identify genes involved in such pathways, with each cluster enriched with the gene ontology (GO). The Centiscape2.0 software was used to calculate the degree of genetic networks and the betweenness value to explore the core node (gene). Weighed gene co-expression network analysis (WGCNA) was then used to explore the co-expression of genes in these pathways.With gene expression data derived from BrainSpan, GO enrichment was carried out for each gene module. Eleven significant biological pathways was identified in association with LBW, among which two (Selenoamino acid metabolism and Diseases associated with glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis. Network analysis of 130 genes in these pathways revealed that some of the sub-networksare related with morphology of cerebellum, development of hippocampus, and plasticity of synaptic structure. Upon co-expression network analysis, 120 genes passed the quality control and were found to express in 3 gene modules. These modules are mainly related to the regulation of synaptic structure and activity regulation. ADHD and LBW share some biological regulation processes. Anomalies of such proces sesmay predispose to ADHD.

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

PubMed

Lam, Max; Trampush, Joey W; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C; Starr, John M; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J; Steen, Vidar M; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Giegling, Ina; Konte, Bettina; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Attix, Deborah K; Need, Anna C; Cirulli, Elizabeth T; Voineskos, Aristotle N; Stefanis, Nikos C; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Arking, Dan E; Smyrnis, Nikolaos; Bilder, Robert M; Freimer, Nelson A; Cannon, Tyrone D; London, Edythe; Poldrack, Russell A; Sabb, Fred W; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A; Dickinson, Dwight; Straub, Richard E; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad R; Weinberger, Daniel R; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C; Andreassen, Ole A; Deary, Ian J; Glahn, David C; Malhotra, Anil K; Lencz, Todd

2017-11-28

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Statistical assessment of crosstalk enrichment between gene groups in biological networks.

PubMed

McCormack, Theodore; Frings, Oliver; Alexeyenko, Andrey; Sonnhammer, Erik L L

2013-01-01

Analyzing groups of functionally coupled genes or proteins in the context of global interaction networks has become an important aspect of bioinformatic investigations. Assessing the statistical significance of crosstalk enrichment between or within groups of genes can be a valuable tool for functional annotation of experimental gene sets. Here we present CrossTalkZ, a statistical method and software to assess the significance of crosstalk enrichment between pairs of gene or protein groups in large biological networks. We demonstrate that the standard z-score is generally an appropriate and unbiased statistic. We further evaluate the ability of four different methods to reliably recover crosstalk within known biological pathways. We conclude that the methods preserving the second-order topological network properties perform best. Finally, we show how CrossTalkZ can be used to annotate experimental gene sets using known pathway annotations and that its performance at this task is superior to gene enrichment analysis (GEA). CrossTalkZ (available at http://sonnhammer.sbc.su.se/download/software/CrossTalkZ/) is implemented in C++, easy to use, fast, accepts various input file formats, and produces a number of statistics. These include z-score, p-value, false discovery rate, and a test of normality for the null distributions.

Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein,more » we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.« less

Microarray gene-expression study in fibroblast and lymphoblastoid cell lines from antipsychotic-naïve first-episode schizophrenia patients.

PubMed

Gassó, Patricia; Mas, Sergi; Rodríguez, Natalia; Boloc, Daniel; García-Cerro, Susana; Bernardo, Miquel; Lafuente, Amalia; Parellada, Eduard

2017-12-01

Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls. We used an analytical approach based on protein-protein interaction network construction and functional annotation analysis to identify the biological processes that are altered in SZ. Significant differences in the expression of 32 genes were found when LCLs were assessed. The network and gene set enrichment approach revealed the involvement of similar biological processes in FCLs and LCLs, including apoptosis and related biological terms such as cell cycle, autophagy, cytoskeleton organization and response to stress and stimulus. Metabolism and other processes, including signal transduction, kinase activity and phosphorylation, were also identified. These results were replicated in two independent cohorts using the same analytical approach. This provides more evidence for altered apoptotic processes in antipsychotic-naïve FES patients and other important biological functions such as cytoskeleton organization and metabolism. The convergent results obtained in both peripheral cell models support their usefulness for transcriptome studies on SZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and Evaluation of a Novel Adenosine-Ribose Probe for Global-Scale Profiling of Nucleoside and Nucleotide-Binding Proteins

PubMed Central

Mahajan, Shikha; Manetsch, Roman; Merkler, David J.; Stevens Jr., Stanley M.

2015-01-01

Proteomics is a powerful approach used for investigating the complex molecular mechanisms of disease pathogenesis and progression. An important challenge in modern protein profiling approaches involves targeting of specific protein activities in order to identify altered molecular processes associated with disease pathophysiology. Adenosine-binding proteins represent an important subset of the proteome where aberrant expression or activity changes of these proteins have been implicated in numerous human diseases. Herein, we describe an affinity-based approach for the enrichment of adenosine-binding proteins from a complex cell proteome. A novel N 6-biotinylated-8-azido-adenosine probe (AdoR probe) was synthesized, which contains a reactive group that forms a covalent bond with the target proteins, as well as a biotin tag for affinity enrichment using avidin chromatography. Probe specificity was confirmed with protein standards prior to further evaluation in a complex protein mixture consisting of a lysate derived from mouse neuroblastoma N18TG2 cells. Protein identification and relative quantitation using mass spectrometry allowed for the identification of small variations in abundance of nucleoside- and nucleotide-binding proteins in these samples where a significant enrichment of AdoR-binding proteins in the labeled proteome from the neuroblastoma cells was observed. The results from this study demonstrate the utility of this method to enrich for nucleoside- and nucleotide-binding proteins in a complex protein mixture, pointing towards a unique set of proteins that can be examined in the context of further understanding mechanisms of disease, or fundamental biological processes in general. PMID:25671571

Hybrid coexpression link similarity graph clustering for mining biological modules from multiple gene expression datasets

PubMed Central

2014-01-01

Background Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. Results We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways. PMID:25221624

Vascular Cells in Blood Vessel Wall Development and Disease.

PubMed

Mazurek, R; Dave, J M; Chandran, R R; Misra, A; Sheikh, A Q; Greif, D M

2017-01-01

The vessel wall is composed of distinct cellular layers, yet communication among individual cells within and between layers results in a dynamic and versatile structure. The morphogenesis of the normal vascular wall involves a highly regulated process of cell proliferation, migration, and differentiation. The use of modern developmental biological and genetic approaches has markedly enriched our understanding of the molecular and cellular mechanisms underlying these developmental events. Additionally, the application of similar approaches to study diverse vascular diseases has resulted in paradigm-shifting insights into pathogenesis. Further investigations into the biology of vascular cells in development and disease promise to have major ramifications on therapeutic strategies to combat pathologies of the vasculature. © 2017 Elsevier Inc. All rights reserved.

Integrating data from biological experiments into metabolic networks with the DBE information system.

PubMed

Borisjuk, Ljudmilla; Hajirezaei, Mohammad-Reza; Klukas, Christian; Rolletschek, Hardy; Schreiber, Falk

2005-01-01

Modern 'omics'-technologies result in huge amounts of data about life processes. For analysis and data mining purposes this data has to be considered in the context of the underlying biological networks. This work presents an approach for integrating data from biological experiments into metabolic networks by mapping the data onto network elements and visualising the data enriched networks automatically. This methodology is implemented in DBE, an information system that supports the analysis and visualisation of experimental data in the context of metabolic networks. It consists of five parts: (1) the DBE-Database for consistent data storage, (2) the Excel-Importer application for the data import, (3) the DBE-Website as the interface for the system, (4) the DBE-Pictures application for the up- and download of binary (e. g. image) files, and (5) DBE-Gravisto, a network analysis and graph visualisation system. The usability of this approach is demonstrated in two examples.

Application of 15N-enrichment methodologies to estimate nitrogen fixation in Casuarina equisetifolia

Treesearch

John A. Parrotta; Dwight D. Baker; Maurice Fried

1994-01-01

The 15N-enrichment technique for estimating biological nitrogen fixation in Casuarina equisetifolia J.R. & G. Forst. was evaluated under field conditions in single-species and mixed-species plantings (with a nonfixing reference species, Eucalyptus X robusta J.E. Smith) between...

Comparative muscle transcriptome associated with carcass traits of Nellore cattle.

PubMed

Silva-Vignato, Bárbara; Coutinho, Luiz L; Cesar, Aline S M; Poleti, Mirele D; Regitano, Luciana C A; Balieiro, Júlio C C

2017-07-03

Commercial cuts yield is an important trait for beef production, which affects the final value of the products, but its direct determination is a challenging procedure to be implemented in practice. The measurement of ribeye area (REA) and backfat thickness (BFT) can be used as indirect measures of meat yield. REA and BFT are important traits studied in beef cattle due to their strong implication in technological (carcass yield) and nutritional characteristics of meat products, like the degree of muscularity and total body fat. Thus, the aim of this work was to study the Longissimus dorsi muscle transcriptome of Nellore cattle, associated with REA and BFT, to find differentially expressed (DE) genes, metabolic pathways, and biological processes that may regulate these traits. By comparing the gene expression level between groups with extreme genomic estimated breeding values (GEBV), 101 DE genes for REA and 18 for BFT (false discovery rate, FDR 10%) were identified. Functional enrichment analysis for REA identified two KEGG pathways, MAPK (Mitogen-Activated Protein Kinase) signaling pathway and endocytosis pathway, and three biological processes, response to endoplasmic reticulum stress, cellular protein modification process, and macromolecule modification. The MAPK pathway is responsible for fundamental cellular processes, such as growth, differentiation, and hypertrophy. For BFT, 18 biological processes were found to be altered and grouped into 8 clusters of semantically similar terms. The DE genes identified in the biological processes for BFT were ACHE, SRD5A1, RSAD2 and RSPO3. RSAD2 has been previously shown to be associated with lipid droplet content and lipid biosynthesis. In this study, we identified genes, metabolic pathways, and biological processes, involved in differentiation, proliferation, protein turnover, hypertrophy, as well as adipogenesis and lipid biosynthesis related to REA and BFT. These results enlighten some of the molecular processes involved in muscle and fat deposition, which are economically important carcass traits for beef production.

Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

PubMed

Galassie, Allison C; Goll, Johannes B; Samir, Parimal; Jensen, Travis L; Hoek, Kristen L; Howard, Leigh M; Allos, Tara M; Niu, Xinnan; Gordy, Laura E; Creech, C Buddy; Hill, Heather; Joyce, Sebastian; Edwards, Kathryn M; Link, Andrew J

2017-06-01

Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer cells, T cells, and B cells after administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA class I proteins was increased in the Adjuvant System 03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biology Modules for the Visually Handicapped.

ERIC Educational Resources Information Center

Allan, Douglas M.

The instructional materials presented and described in this document were prepared as part of a project to develop enrichment materials for visually impaired biology students. A wide range of biology topics are presented, including most subjects covered in a one-semester course for nonmajors. Typewritten handouts, duplicating the content of…

Disciplinary Authenticity: Enriching the Reforms of Introductory Physics Courses for Life-Science Students

ERIC Educational Resources Information Center

Watkins, Jessica; Coffey, Janet E.; Redish, Edward F.; Cooke, Todd J.

2012-01-01

Educators and policy makers have advocated for reform of undergraduate biology education, calling for greater integration of mathematics and physics in the biology curriculum. While these calls reflect the increasingly interdisciplinary nature of biology research, crossing disciplinary boundaries in the classroom carries epistemological challenges…

Silylated Derivatives Retain Carbon and Alter Expected 13C-Tracer Enrichments Using Continuous Flow-Combustion-Isotope Ratio Mass Spectrometry

PubMed Central

Shinebarger, Steven R.; Haisch, Michael; Matthews, Dwight E.

2008-01-01

Continuous-flow inlets from oxidation reactors are commonly used systems for biological sample introduction into isotope ratio mass spectrometers (IRMS) to measure 13C enrichment above natural abundance. Because the samples must be volatile enough to pass through a gas chromatograph, silylated derivatization reactions are commonly used to modify biological molecules to add the necessary volatility. Addition of a t-butyldimethylsilyl (TBDMS) group is a common derivatization approach. However, we have found that samples do not produce the expected increment in measured 13C abundance as the TBDMS derivatives. We have made measurements of 13C enrichment of leucine and glutamate standards of known 13C enrichment using derivatives without silicon (N-acetyl n-propyl ester), with silicon (TBDMS), and an intermediate case. The measurements of 13C in amino acids derivatized without silicon were as expected. The 13C enrichment measurements using the TBDMS derivative were higher than expected, but could be corrected to produce the expected 13C enrichment measurement by IRMS if one carbon was removed per silicon. We postulate that the silicon in the derivative forms silicon carbide compounds in the heated cupric oxide reactor, rather than forming silicon dioxide. Doing so reduces the amount of CO2 formed from the carbon in the sample. Silylated derivatives retain carbon with the silicon and must be used carefully and with correction factors to measure 13C enrichments by continuous-flow IRMS. PMID:12510745

Robust, Sensitive, and Automated Phosphopeptide Enrichment Optimized for Low Sample Amounts Applied to Primary Hippocampal Neurons.

PubMed

Post, Harm; Penning, Renske; Fitzpatrick, Martin A; Garrigues, Luc B; Wu, W; MacGillavry, Harold D; Hoogenraad, Casper C; Heck, Albert J R; Altelaar, A F Maarten

2017-02-03

Because of the low stoichiometry of protein phosphorylation, targeted enrichment prior to LC-MS/MS analysis is still essential. The trend in phosphoproteome analysis is shifting toward an increasing number of biological replicates per experiment, ideally starting from very low sample amounts, placing new demands on enrichment protocols to make them less labor-intensive, more sensitive, and less prone to variability. Here we assessed an automated enrichment protocol using Fe(III)-IMAC cartridges on an AssayMAP Bravo platform to meet these demands. The automated Fe(III)-IMAC-based enrichment workflow proved to be more effective when compared to a TiO 2 -based enrichment using the same platform and a manual Ti(IV)-IMAC-based enrichment workflow. As initial samples, a dilution series of both human HeLa cell and primary rat hippocampal neuron lysates was used, going down to 0.1 μg of peptide starting material. The optimized workflow proved to be efficient, sensitive, and reproducible, identifying, localizing, and quantifying thousands of phosphosites from just micrograms of starting material. To further test the automated workflow in genuine biological applications, we monitored EGF-induced signaling in hippocampal neurons, starting with only 200 000 primary cells, resulting in ∼50 μg of protein material. This revealed a comprehensive phosphoproteome, showing regulation of multiple members of the MAPK pathway and reduced phosphorylation status of two glutamate receptors involved in synaptic plasticity.

Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

PubMed

Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

2017-03-15

Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

Differential Modulation of Photosynthesis, Signaling, and Transcriptional Regulation between Tolerant and Sensitive Tomato Genotypes under Cold Stress

PubMed Central

Zhang, Junhong; Wang, Taotao; Li, Hanxia; Zhang, Yuyang; Yu, Chuying; Ye, Zhibiao

2012-01-01

The wild species Solanum habrochaites is more cold tolerant than the cultivated tomato (S. lycopersicum). To explore the mechanisms underlying cold tolerance of S. habrochaites, seedlings of S. habrochaites LA1777 introgression lines (ILs), as well as the two parents, were evaluated under low temperature (4°C). The IL LA3969 and its donor parent LA1777 were found to be more cold tolerant than the recurrent parent S. lycopersicum LA4024. The differences in physiology and global gene expression between cold-tolerant (LA1777 and LA3969) and -sensitive (LA4024) genotypes under cold stress were further investigated. Comparative transcriptome analysis identified 1613, 1456, and 1523 cold-responsive genes in LA1777, LA3969, and LA4024, respectively. Gene ontology (GO) term enrichment analysis revealed that more GO biological process terms were significantly enriched among the up-regulated genes in the two tolerant genotypes, whereas more biological processes were significantly repressed by cold stress in the sensitive one. A total of 92 genes with significant differential expression between tolerant and sensitive genotypes under cold stress were identified. Among these, many stress-related GO terms were significantly enriched, such as ‘response to stimulus’ and ‘response to stress’. Moreover, GO terms ‘response to hormone stimulus’, ‘response to reactive oxygen species (ROS)’, and ‘calcium-mediated signaling’ were also overrepresented. Several transcripts involved in hormone or ROS homeostasis were also differentially expressed. ROS, hormones, and calcium as signaling molecules may play important roles in regulating gene expression in response to cold stress. Moreover, the expression of various transcription factors, post-translational proteins, metabolic enzymes, and photosynthesis-related genes was also specifically modulated. These specific modifications may play pivotal roles in conferring cold tolerance in tomato. These results not only provide new insights into the molecular mechanisms of cold tolerance in tomato, but also provide potential candidate genes for genetic improvement. PMID:23226384

Estimation of nitrogen fixation in Leucaena leucocephala using 15N-enrichment methodologies

Treesearch

John A. Parrotta; Dwight D. Baker; Maurice Fried

1994-01-01

An estimation of biological nitrogen fixation by Leucaena leucocephala (Lam.) de Wit in monoculture and mixed-species plantations (with Casuarina equisetifolia L. ex J.R. & G. Forst., and Eucalyptus robusta Sm.) was undertaken over a two-year period in Puerto Rico using the 15N-enrichment...

Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

PubMed Central

Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

2014-01-01

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

Comprehensive profiling of lysine acetylation suggests the widespread function is regulated by protein acetylation in the silkworm, Bombyx mori.

PubMed

Nie, Zuoming; Zhu, Honglin; Zhou, Yong; Wu, Chengcheng; Liu, Yue; Sheng, Qing; Lv, Zhengbing; Zhang, Wenping; Yu, Wei; Jiang, Caiying; Xie, Longfei; Zhang, Yaozhou; Yao, Juming

2015-09-01

Lysine acetylation in proteins is a dynamic and reversible PTM and plays an important role in diverse cellular processes. In this study, using lysine-acetylation (Kac) peptide enrichment coupled with nano HPLC/MS/MS, we initially identified the acetylome in the silkworms. Overall, a total of 342 acetylated proteins with 667 Kac sites were identified in silkworm. Sequence motifs analysis around Kac sites revealed an enrichment of Y, F, and H in the +1 position, and F was also enriched in the +2 and -2 positions, indicating the presences of preferred amino acids around Kac sites in the silkworm. Functional analysis showed the acetylated proteins were primarily involved in some specific biological processes. Furthermore, lots of nutrient-storage proteins, such as apolipophorin, vitellogenin, storage proteins, and 30 K proteins, were highly acetylated, indicating lysine acetylation may represent a common regulatory mechanism of nutrient utilization in the silkworm. Interestingly, Ser2 proteins, the coating proteins of larval silk, were found to contain many Kac sites, suggesting lysine acetylation may be involved in the regulation of larval silk synthesis. This study is the first to identify the acetylome in a lepidoptera insect, and expands greatly the catalog of lysine acetylation substrates and sites in insects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The relative importance of light and nutrient limitation of phytoplankton growth: A simple index of coastal ecosystem sensitivity to nutrient enrichment

USGS Publications Warehouse

Cloern, J.E.

1999-01-01

Anthropogenic nutrient enrichment of the coastal zone is now a well-established fact. However, there is still uncertainty about the mechanisms through which nutrient enrichment can disrupt biological communities and ecosystem processes in the coastal zone. For example, while some estuaries exhibit classic symptoms of acute eutrophication, including enhanced production of algal biomass, other nutrient-rich estuaries maintain low algal biomass and primary production. This implies that large differences exist among coastal ecosystems in the rates and patterns of nutrient assimilation and cycling. Part of this variability comes from differences among ecosystems in the other resource that can limit algal growth and production - the light energy required for photosynthesis. Complete understanding of the eutrophication process requires consideration of the interacting effects of light and nutrients, including the role of light availability as a regulator of the expression of eutrophication. A simple index of the relative strength of light and nutrient limitation of algal growth can be derived from models that describe growth rate as a function of these resources. This index can then be used as one diagnostic to classify the sensitivity of coastal ecosystems to the harmful effects of eutrophication. Here I illustrate the application of this diagnostic with light and nutrient measurements made in three California estuaries and two Dutch estuaries.

SigWin-detector: a Grid-enabled workflow for discovering enriched windows of genomic features related to DNA sequences.

PubMed

Inda, Márcia A; van Batenburg, Marinus F; Roos, Marco; Belloum, Adam S Z; Vasunin, Dmitry; Wibisono, Adianto; van Kampen, Antoine H C; Breit, Timo M

2008-08-08

Chromosome location is often used as a scaffold to organize genomic information in both the living cell and molecular biological research. Thus, ever-increasing amounts of data about genomic features are stored in public databases and can be readily visualized by genome browsers. To perform in silico experimentation conveniently with this genomics data, biologists need tools to process and compare datasets routinely and explore the obtained results interactively. The complexity of such experimentation requires these tools to be based on an e-Science approach, hence generic, modular, and reusable. A virtual laboratory environment with workflows, workflow management systems, and Grid computation are therefore essential. Here we apply an e-Science approach to develop SigWin-detector, a workflow-based tool that can detect significantly enriched windows of (genomic) features in a (DNA) sequence in a fast and reproducible way. For proof-of-principle, we utilize a biological use case to detect regions of increased and decreased gene expression (RIDGEs and anti-RIDGEs) in human transcriptome maps. We improved the original method for RIDGE detection by replacing the costly step of estimation by random sampling with a faster analytical formula for computing the distribution of the null hypothesis being tested and by developing a new algorithm for computing moving medians. SigWin-detector was developed using the WS-VLAM workflow management system and consists of several reusable modules that are linked together in a basic workflow. The configuration of this basic workflow can be adapted to satisfy the requirements of the specific in silico experiment. As we show with the results from analyses in the biological use case on RIDGEs, SigWin-detector is an efficient and reusable Grid-based tool for discovering windows enriched for features of a particular type in any sequence of values. Thus, SigWin-detector provides the proof-of-principle for the modular e-Science based concept of integrative bioinformatics experimentation.

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†.

PubMed

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-08-15

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. © The Author 2015. Published by Oxford University Press.

Extensive Determination of Glycan Heterogeneity Reveals an Unusual Abundance of High Mannose Glycans in Enriched Plasma Membranes of Human Embryonic Stem Cells*

PubMed Central

An, Hyun Joo; Gip, Phung; Kim, Jaehan; Wu, Shuai; Park, Kun Wook; McVaugh, Cheryl T.; Schaffer, David V.; Bertozzi, Carolyn R.; Lebrilla, Carlito B.

2012-01-01

Most cell membrane proteins are known or predicted to be glycosylated in eukaryotic organisms, where surface glycans are essential in many biological processes including cell development and differentiation. Nonetheless, the glycosylation on cell membranes remains not well characterized because of the lack of sensitive analytical methods. This study introduces a technique for the rapid profiling and quantitation of N- and O-glycans on cell membranes using membrane enrichment and nanoflow liquid chromatography/mass spectrometry of native structures. Using this new method, the glycome analysis of cell membranes isolated from human embryonic stem cells and somatic cell lines was performed. Human embryonic stem cells were found to have high levels of high mannose glycans, which contrasts with IMR-90 fibroblasts and a human normal breast cell line, where complex glycans are by far the most abundant and high mannose glycans are minor components. O-Glycosylation affects relatively minor components of cell surfaces. To verify the quantitation and localization of glycans on the human embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed. Proteomics analyses were also performed and confirmed enrichment of plasma membrane proteins with some contamination from endoplasmic reticulum and other membranes. These findings suggest that high mannose glycans are the major component of cell surface glycosylation with even terminal glucoses. High mannose glycans are not commonly presented on the surfaces of mammalian cells or in serum yet may play important roles in stem cell biology. The results also mean that distinguishing stem cells from other mammalian cells may be facilitated by the major difference in the glycosylation of the cell membrane. The deep structural analysis enabled by this new method will enable future mechanistic studies on the biological significance of high mannose glycans on stem cell membranes and provide a general tool to examine cell surface glycosylation. PMID:22147732

Key issues concerning environmental enrichment for laboratory-held fish species.

PubMed

Williams, T D; Readman, G D; Owen, S F

2009-04-01

An improved knowledge and understanding of the fundamental biological requirements is needed for many of the species of fish held in captivity and, without this knowledge it is difficult to determine the optimal conditions for laboratory culture. The aim of this paper is to review the key issues concerning environmental enrichment for laboratory-held fish species and identify where improvements are required. It provides background information on environmental enrichment, describes enrichment techniques currently used in aquatic ecotoxicology studies, identifies potential restrictions in their use and discusses why more detailed and species-specific guidance is needed.

Startup pattern and performance enhancement of pilot-scale biofilm process for raw water pretreatment.

PubMed

Yang, Guang-Feng; Feng, Li-Juan; Yang, Qi; Zhu, Liang; Xu, Jian; Xu, Xiang-Yang

2014-11-01

The quality of raw water is getting worse in developing countries because of the inadequate treatment of municipal sewage, industrial wastewater and agricultural runoff. Aiming at the biofilm enrichment and pollutant removal, two pilot-scale biofilm reactors were built with different biological carriers. Results showed that compared with the blank carrier, the biofilm was easily enriched on the biofilm precoated carrier and less nitrite accumulation occurred. The removal efficiencies of NH4(+)-N, DOC and UV254 increased under the aeration condition, and a optimum DO level for the adequate nitrification was 1.0-2.6mgL(-1) with the suitable temperature range of 21-22°C. Study on the trihalomethane prediction model indicated that the presentence of algae increased the risk of disinfection by-products production, which could be effectively controlled via manual algae removing and light shading. In this study, the performance of biofilm pretreatment process could be enhanced under the optimized condition of DO level and biofilm carrier. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integration of Population-Level Genotype Data with Functional Annotation Reveals Over-Representation of Long Noncoding RNAs at Ovarian Cancer Susceptibility Loci.

PubMed

Reid, Brett M; Permuth, Jennifer B; Chen, Y Ann; Teer, Jamie K; Monteiro, Alvaro N A; Chen, Zhihua; Tyrer, Jonathan; Berchuck, Andrew; Chenevix-Trench, Georgia; Doherty, Jennifer A; Goode, Ellen L; Iverson, Edwin S; Lawrenson, Kate; Pearce, Celeste L; Pharoah, Paul D; Phelan, Catherine M; Ramus, Susan J; Rossing, Mary Anne; Schildkraut, Joellen M; Cheng, Jin Q; Gayther, Simon A; Sellers, Thomas A

2017-01-01

Genome-wide association studies (GWAS) have identified multiple loci associated with epithelial ovarian cancer (EOC) susceptibility, but further progress requires integration of epidemiology and biology to illuminate true risk loci below genome-wide significance levels (P < 5 × 10 -8 ). Most risk SNPs lie within non-protein-encoding regions, and we hypothesize that long noncoding RNA (lncRNA) genes are enriched at EOC risk regions and represent biologically relevant functional targets. Using imputed GWAS data from about 18,000 invasive EOC cases and 34,000 controls of European ancestry, the GENCODE (v19) lncRNA database was used to annotate SNPs from 13,442 lncRNAs for permutation-based enrichment analysis. Tumor expression quantitative trait locus (eQTL) analysis was performed for sub-genome-wide regions (1 × 10 -5 > P > 5 × 10 -8 ) overlapping lncRNAs. Of 5,294 EOC-associated SNPs (P < 1.0 × 10 -5 ), 1,464 (28%) mapped within 53 unique lncRNAs and an additional 3,484 (66%) SNPs were correlated (r 2 > 0.2) with SNPs within 115 lncRNAs. EOC-associated SNPs comprised 130 independent regions, of which 72 (55%) overlapped with lncRNAs, representing a significant enrichment (P = 5.0 × 10 -4 ) that was more pronounced among a subset of 5,401 lncRNAs with active epigenetic regulation in normal ovarian tissue. EOC-associated lncRNAs and their putative promoters and transcription factors were enriched for biologically relevant pathways and eQTL analysis identified five novel putative risk regions with allele-specific effects on lncRNA gene expression. lncRNAs are significantly enriched at EOC risk regions, suggesting a mechanistic role for lncRNAs in driving predisposition to EOC. lncRNAs represent key candidates for integrative epidemiologic and functional studies. Further research on their biologic role in ovarian cancer is indicated. Cancer Epidemiol Biomarkers Prev; 26(1); 116-25. ©2016 AACR. ©2016 American Association for Cancer Research.

GEAR: genomic enrichment analysis of regional DNA copy number changes.

PubMed

Kim, Tae-Min; Jung, Yu-Chae; Rhyu, Mun-Gan; Jung, Myeong Ho; Chung, Yeun-Jun

2008-02-01

We developed an algorithm named GEAR (genomic enrichment analysis of regional DNA copy number changes) for functional interpretation of genome-wide DNA copy number changes identified by array-based comparative genomic hybridization. GEAR selects two types of chromosomal alterations with potential biological relevance, i.e. recurrent and phenotype-specific alterations. Then it performs functional enrichment analysis using a priori selected functional gene sets to identify primary and clinical genomic signatures. The genomic signatures identified by GEAR represent functionally coordinated genomic changes, which can provide clues on the underlying molecular mechanisms related to the phenotypes of interest. GEAR can help the identification of key molecular functions that are activated or repressed in the tumor genomes leading to the improved understanding on the tumor biology. GEAR software is available with online manual in the website, http://www.systemsbiology.co.kr/GEAR/.

Comprehensive analysis of genetic variations in strictly-defined Leber congenital amaurosis with whole-exome sequencing in Chinese

PubMed Central

Wang, Shi-Yuan; Zhang, Qi; Zhang, Xiang; Zhao, Pei-Quan

2016-01-01

AIM To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis (LCA) in Chinese. METHODS LCA subjects and their families were retrospectively collected from 2013 to 2015. Firstly, whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found, and then homozygous sites was selected, candidate sites were annotated, and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant (SIFT), Polyphen-2, Mutation assessor, Condel, and Functional Analysis through Hidden Markov Models (FATHMM). Furthermore, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test. Sanger sequencing was used to validate single-nucleotide variations (SNVs). Expanded verification was performed in the rest patients. RESULTS Totally 51 LCA families with 53 patients and 24 family members were recruited. A total of 104 SNVs (66 LCA-related genes and 15 co-segregated genes) were submitted for expand verification. The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families. Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion, biological adhesion, retinoid metabolic process, and eye development biological adhesion. Additionally, WFS1 and STAU2 had the highest homozygous frequencies. CONCLUSION LCA is a highly heterogeneous disease. Mutations in KRT12, CYP1A1, WFS1, and STAU2 may be involved in the development of LCA. PMID:27672588

Identification of potential crucial genes associated with steroid-induced necrosis of femoral head based on gene expression profile.

PubMed

Lin, Zhe; Lin, Yongsheng

2017-09-05

The aim of this study was to explore potential crucial genes associated with the steroid-induced necrosis of femoral head (SINFH) and to provide valid biological information for further investigation of SINFH. Gene expression profile of GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using LIMMA package. After functional enrichment analyses of DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted based on the STRING database and cytoscape. In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up-regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and Il7R), and the downregulated DEGs were mainly enriched in muscle system process (e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and 300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based on both subgraph centrality and degree centrality evaluation. These three genes interacted with each other in the network. Furthermore, the significant network module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These genes were mainly enriched in functions like muscle system process. The DEGs related to the regulation of immune system process (e.g. Fcer1A and Il7R), and DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be closely associated with the progress of SINFH, which is still needed to be confirmed by experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of chlorate on the sulfation process of Trypanosoma cruzi glycoconjugates. Implication of parasite sulfates in cellular invasion.

PubMed

Ferrero, Maximiliano R; Soprano, Luciana L; Acosta, Diana M; García, Gabriela A; Esteva, Mónica I; Couto, Alicia S; Duschak, Vilma G

2014-09-01

Sulfation, a post-translational modification which plays a key role in various biological processes, is inhibited by competition with chlorate. In Trypanosoma cruzi, the agent of Chagas' disease, sulfated structures have been described as part of glycolipids and we have reported sulfated high-mannose type oligosaccharides in the C-T domain of the cruzipain (Cz) glycoprotein. However, sulfation pathways have not been described yet in this parasite. Herein, we studied the effect of chlorate treatment on T. cruzi with the aim to gain some knowledge about sulfation metabolism and the role of sulfated molecules in this parasite. In chlorate-treated epimastigotes, immunoblotting with anti-sulfates enriched Cz IgGs (AS-enriched IgGs) showed Cz undersulfation. Accordingly, a Cz mobility shift toward higher isoelectric points was observed in 2D-PAGE probed with anti-Cz antibodies. Ultrastructural membrane abnormalities and a significant decrease of dark lipid reservosomes were shown by electron microscopy and a significant decrease in sulfatide levels was confirmed by TLC/UV-MALDI-TOF-MS analysis. Altogether, these results suggest T. cruzi sulfation occurs via PAPS. Sulfated epitopes in trypomastigote and amastigote forms were evidenced using AS-enriched IgGs by immunoblotting. Their presence on trypomastigotes surface was demonstrated by flow cytometry and IF with Cz/dCz specific antibodies. Interestingly, the percentage of infected cardiac HL-1 cells decreased 40% when using chlorate-treated trypomastigotes, suggesting sulfates are involved in the invasion process. The same effect was observed when cells were pre-incubated with dCz, dC-T or an anti-high mannose receptor (HMR) antibody, suggesting Cz sulfates and HMR are also involved in the infection process by T. cruzi. Copyright © 2014 Elsevier B.V. All rights reserved.

Spatial distribution and potential biological risk of some metals in relation to granulometric content in core sediments from Chilika Lake, India.

PubMed

Barik, Saroja K; Muduli, Pradipta R; Mohanty, Bita; Rath, Prasanta; Samanta, Srikanta

2018-01-01

The article presents first systematic report on the concentration of selected major elements [iron (Fe) and manganese (Mn)] and minor elements [zinc (Zn), copper (Cu), chromium (Cr), lead (Pb), nickel (Ni), and cobalt (Co)] from the core sediment of Chilika Lake, India. The analyzed samples revealed higher content of Pb than the background levels in the entire study area. The extent of contamination from minor and major elements is expressed by assessing (i) the metal enrichments in the sediment through the calculations of anthropogenic factor (AF), pollution load index (PLI), Enrichment factor (EF), and geoaccumulation index (Igeo) and (ii) potential biological risks by the use of sediment quality guidelines like effect range median (ERM) and effect range low (ERL) benchmarks. The estimated indices indicated that sediment is enriched with Pb, Ni, Cr, Cu and Co. The enrichment of these elements seems to be due to the fine granulometric characteristics of the sediment with Fe and Mn oxyhydroxides being the main metal carriers and fishing boats using low grade paints, fuel, and fishing technology using lead beads fixed to fishing nets. Trace element input to the Chilika lake needs to be monitored with due emphasis on Cr and Pb contaminations since the ERM and ERL benchmarks indicated potential biological risk with these metals.

Development and modelling of a steel slag filter effluent neutralization process with CO2-enriched air from an upstream bioprocess.

PubMed

Bove, Patricia; Claveau-Mallet, Dominique; Boutet, Étienne; Lida, Félix; Comeau, Yves

2018-02-01

The main objective of this project was to develop a steel slag filter effluent neutralization process by acidification with CO 2 -enriched air coming from a bioprocess. Sub-objectives were to evaluate the neutralization capacity of different configurations of neutralization units in lab-scale conditions and to propose a design model of steel slag effluent neutralization. Two lab-scale column neutralization units fed with two different types of influent were operated at hydraulic retention time of 10 h. Tested variables were mode of flow (saturated or percolating), type of media (none, gravel, Bionest and AnoxKaldnes K3), type of air (ambient or CO 2 -enriched) and airflow rate. One neutralization field test (saturated and no media, 2000-5000 ppm CO 2 , sequential feeding, hydraulic retention time of 7.8 h) was conducted for 7 days. Lab-scale and field-scale tests resulted in effluent pH of 7.5-9.5 when the aeration rate was sufficiently high. A model was implemented in the PHREEQC software and was based on the carbonate system, CO 2 transfer and calcite precipitation; and was calibrated on ambient air lab tests. The model was validated with CO 2 -enriched air lab and field tests, providing satisfactory validation results over a wide range of CO 2 concentrations. The flow mode had a major impact on CO 2 transfer and hydraulic efficiency, while the type of media had little influence. The flow mode also had a major impact on the calcite surface concentration in the reactor: it was constant in saturated mode and was increasing in percolating mode. Predictions could be made for different steel slag effluent pH and different operation conditions (hydraulic retention time, CO 2 concentration, media and mode of flow). The pH of the steel slag filter effluent and the CO 2 concentration of the enriched air were factors that influenced most the effluent pH of the neutralization process. An increased concentration in CO 2 in the enriched air reduced calcite precipitation and clogging risks. Stoichiometric calculations showed that a typical domestic septic tank effluent with 300 mg/L of biodegradable COD provides enough biological CO 2 for neutralization of a steel slag effluent with pH of 10.5-11.5. A saturated neutralization reactor with no media operated at hydraulic retention time of 10 h and a concentration of 2000 ppm in CO 2 enriched air is recommended for full-scale applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isotope pattern deconvolution as rising tool for isotope tracer studies in environmental research

NASA Astrophysics Data System (ADS)

Irrgeher, Johanna; Zitek, Andreas; Prohaska, Thomas

2014-05-01

During the last decade stable isotope tracers have emerged as versatile tool in ecological research. Besides 'intrinsic' isotope tracers caused by the natural variation of isotopes, the intentional introduction of 'extrinsic' enriched stable isotope tracers into biological systems has gained significant interest. Hereby the induced change in the natural isotopic composition of an element allows amongst others for studying the fate and fluxes of metals, trace elements and species in organisms or provides an intrinsic marker or tag of particular biological samples. Due to the shoreless potential of this methodology, the number of publications dealing with applications of isotope (double) spikes as tracers to address research questions in 'real world systems' is constantly increasing. However, some isotope systems like the natural Sr isotopic system, although potentially very powerful for this type of application, are still rarely used, mainly because their adequate measurement/determination poses major analytical challenges; as e.g. Sr is available in significant amounts in natural samples. In addition, biological systems underlie complex processes such as metabolism, adsorption/desorption or oxidation/reduction. As a consequence, classic evaluation approaches such as the isotope dilution mass spectrometry equation are often not applicable because of the unknown amount of tracer finally present in the sample. Isotope pattern deconvolution (IPD), based on multiple linear regression, serves as simplified alternative data processing strategy to double spike isotope dilution calculations. The outstanding advantage of this mathematical tool lies in the possibility of deconvolving the isotope pattern in a spiked sample without knowing the quantities of enriched isotope tracer being incorporated into the natural sample matrix as well as the degree of impurities and species-interconversion (e.g. from sample preparation). Here, the potential of IPD for environmental tracer studies is critically discussed, where special emphasis is set on evaluating different data processing strategies on the example of enriched stable Sr isotopes.1 The analytical key parameters such as blank (Kr, Sr and Rb), variation of the natural Sr isotopic composition in the sample, mass bias, interferences (Rb) and total combined uncertainty are considered. A full metrological protocol for data processing using IPD is presented based on data gained during two transgenerational marking studies of fish, where the transfer of a Sr isotope double spike (84Sr and 86Sr) from female spawners of common carp (Cyprinus carpio L.) and brown trout (Salmo trutta f.f.)2 to the centre of the otoliths of their offspring was studied by (LA)-MC-ICP-MS. 1J. Irrgeher, A. Zitek, M. Cervicek and T. Prohaska, J. Anal. At. Spectrom., 2014, 29, 193-200. 2A. Zitek, J. Irrgeher, M. Kletzl, T. Weismann and T. Prohaska, Fish. Manage. Ecol., 2013, 20, 654-361.

Boron isotopes at the catchment scale, a new potential tool to infer critical zone processes.

NASA Astrophysics Data System (ADS)

Gaillardet, J.; Noireaux, J.; Braun, J. J.; Riotte, J.; Louvat, P.; Bouchez, J.; Lemarchand, D.; Muddu, S.; Mohan Kumar, M.; Candaudap, F.

2017-12-01

Boron is a mid-mass element that has two isotopes, 10B and 11B. These isotopes are largely fractioned by a number of chemical, biological and physical processes. Boron as a great affinity for clays and is useful for life, making it a double tracer of critical zone processes. This study focuses on the Mule Hole Critical Zone Observatory in South India. This is part of the French Research Infrastructure OZCAR and has benefited from the fruitful Indo-French collaboration (Indo-French Cell for Water Sciences) for more that 15 years. Boron and its isotopes were measured in the different compartment of the CZ in Mule Hole, vegetation, atmosphere, throughfall, soil, soil water, river water and compared to the behavior of other elements. The well constrained hydrology in Mule Hole allowed us to calculate the main fluxes affecting boron in the Critical Zone and came to the first order conclusion that the recycling of boron by vegetation is by far the most important flux within the system, reaching 15-20 times the catchment outlet flux. From an isotopic point of view, the total range of variation is measured between -3 ‰ and 77‰, with a bedrock value at 10‰ in classical delta unit, making boron a well suited tracer for constraining CZ processes. The flux of boron most enriched in heavy boron is the throughfall, showing the importance of biological processes in controlling the boron isotopic composition of the stream. Boron in soils in depleted in the heavy isotope but is enriched in boron compared to the bedrock, a surprising situation that we interpret as the legacy of a previous stage of transient weathering. These results indicate a strong decoupling between the behaviors of boron at the surface of the CZ and at depth.

The influence of shelf processes in delivering dissolved iron to the HNLC waters of the Drake Passage, Antarctica

NASA Astrophysics Data System (ADS)

Measures, C. I.; Brown, M. T.; Selph, K. E.; Apprill, A.; Zhou, M.; Hatta, M.; Hiscock, W. T.

2013-06-01

Dissolved trace element distributions near Elephant Island in the Drake Passage show extremely high levels of dissolved Fe and Mn in waters above the shelf. The entrainment of this enriched shelf water by the Fe-poor Antarctic Circumpolar Current (ACC) as it passes through the Shackleton Gap delivers an estimated 2.8×106 mol yr-1 dissolved Fe to the offshore waters of the Drake Passage. The magnitude and spatial distribution of dissolved Fe, Mn and Al over the shelf are consistent with a diagenetically produced sedimentary source, but are inconsistent with eolian or upwelling sources. The systematics of the Mn and Fe concentrations suggest that there are two distinct sources of dissolved Fe to the surface waters of this region. The highest Fe concentrations are associated with Bransfield Strait water, which can be identified by its characteristic temperature and salinity (T/S) properties both inside the Bransfield Strait and in the Bransfield Current outflow between Elephant and Clarence Islands. Most of the shelf area is dominated by a second water type with T/S properties that are typical of modified Antarctic Surface Water, which while also enriched has a lower Fe:Mn ratio. The predominantly linear relationships between the Fe and Mn concentrations at the stations in each of these water mass types suggest that the distribution of these elements is largely controlled by physical mixing processes and that biological removal of Fe on the shelf, while certainly occurring, is limited, perhaps as a result of rapid physical flushing processes and relatively slow biological growth rates. The consequent export of large quantities of this shelf-derived Fe into the ACC is likely responsible for the extensive regions of enhanced primary production seen in satellite imagery downstream of the Drake Passage.

Solar photocatalytic oxidation of recalcitrant natural metabolic by-products of amoxicillin biodegradation.

PubMed

Pereira, João H O S; Reis, Ana C; Homem, Vera; Silva, José A; Alves, Arminda; Borges, Maria T; Boaventura, Rui A R; Vilar, Vítor J P; Nunes, Olga C

2014-11-15

The contamination of the aquatic environment by non-metabolized and metabolized antibiotic residues has brought the necessity of alternative treatment steps to current water decontamination technologies. This work assessed the feasibility of using a multistage treatment system for amoxicillin (AMX) spiked solutions combining: i) a biological treatment process using an enriched culture to metabolize AMX, with ii) a solar photocatalytic system to achieve the removal of the metabolized transformation products (TPs) identified via LC-MS, recalcitrant to further biological degradation. Firstly, a mixed culture (MC) was obtained through the enrichment of an activated sludge sample collected in an urban wastewater treatment plant (WWTP). Secondly, different aqueous matrices spiked with AMX were treated with the MC and the metabolic transformation products were identified. Thirdly, the efficiency of two solar assisted photocatalytic processes (TiO2/UV or Fe(3+)/Oxalate/H2O2/UV-Vis) was assessed in the degradation of the obtained TPs using a lab-scale prototype photoreactor equipped with a compound parabolic collector (CPC). Highest AMX specific biodegradation rates were obtained in buffer and urban wastewater (WW) media (0.10 ± 0.01 and 0.13 ± 0.07 g(AMX) g(biomass)(-1) h(-1), respectively). The resulting TPs, which no longer presented antibacterial activity, were identified as amoxicilloic acid (m/z = 384). The performance of the Fe(3+)/Oxalate/H2O2/UV-Vis system in the removal of the TPs from WW medium was superior to the TiO2/UV process (TPs no longer detected after 40 min (QUV = 2.6 kJ L(-1)), against incomplete TPs removal after 240 min (QUV = 14.9 kJ L(-1)), respectively). Copyright © 2014 Elsevier Ltd. All rights reserved.

Long non-coding RNAs and mRNAs profiling during spleen development in pig.

PubMed

Che, Tiandong; Li, Diyan; Jin, Long; Fu, Yuhua; Liu, Yingkai; Liu, Pengliang; Wang, Yixin; Tang, Qianzi; Ma, Jideng; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

2018-01-01

Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.

Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.

PubMed

Fic, A; Mlakar, S Jurković; Juvan, P; Mlakar, V; Marc, J; Dolenc, M Sollner; Broberg, K; Mašič, L Peterlin

2015-08-01

The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10 nM BPA, BPAF, or BPS, for 8 h and 3 months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bacterial diversity and reductive dehalogenase redundancy in a 1,2-dichloroethane-degrading bacterial consortium enriched from a contaminated aquifer

PubMed Central

2010-01-01

Background Bacteria possess a reservoir of metabolic functionalities ready to be exploited for multiple purposes. The use of microorganisms to clean up xenobiotics from polluted ecosystems (e.g. soil and water) represents an eco-sustainable and powerful alternative to traditional remediation processes. Recent developments in molecular-biology-based techniques have led to rapid and accurate strategies for monitoring and identification of bacteria and catabolic genes involved in the degradation of xenobiotics, key processes to follow up the activities in situ. Results We report the characterization of the response of an enriched bacterial community of a 1,2-dichloroethane (1,2-DCA) contaminated aquifer to the spiking with 5 mM lactate as electron donor in microcosm studies. After 15 days of incubation, the microbial community structure was analyzed. The bacterial 16S rRNA gene clone library showed that the most represented phylogenetic group within the consortium was affiliated with the phylum Firmicutes. Among them, known degraders of chlorinated compounds were identified. A reductive dehalogenase genes clone library showed that the community held four phylogenetically-distinct catalytic enzymes, all conserving signature residues previously shown to be linked to 1,2-DCA dehalogenation. Conclusions The overall data indicate that the enriched bacterial consortium shares the metabolic functionality between different members of the microbial community and is characterized by a high functional redundancy. These are fundamental features for the maintenance of the community's functionality, especially under stress conditions and suggest the feasibility of a bioremediation treatment with a potential prompt dehalogenation and a process stability over time. PMID:20170484

Relating Diseases by Integrating Gene Associations and Information Flow through Protein Interaction Network

PubMed Central

Hamaneh, Mehdi Bagheri; Yu, Yi-Kuo

2014-01-01

Identifying similar diseases could potentially provide deeper understanding of their underlying causes, and may even hint at possible treatments. For this purpose, it is necessary to have a similarity measure that reflects the underpinning molecular interactions and biological pathways. We have thus devised a network-based measure that can partially fulfill this goal. Our method assigns weights to all proteins (and consequently their encoding genes) by using information flow from a disease to the protein interaction network and back. Similarity between two diseases is then defined as the cosine of the angle between their corresponding weight vectors. The proposed method also provides a way to suggest disease-pathway associations by using the weights assigned to the genes to perform enrichment analysis for each disease. By calculating pairwise similarities between 2534 diseases, we show that our disease similarity measure is strongly correlated with the probability of finding the diseases in the same disease family and, more importantly, sharing biological pathways. We have also compared our results to those of MimMiner, a text-mining method that assigns pairwise similarity scores to diseases. We find the results of the two methods to be complementary. It is also shown that clustering diseases based on their similarities and performing enrichment analysis for the cluster centers significantly increases the term association rate, suggesting that the cluster centers are better representatives for biological pathways than the diseases themselves. This lends support to the view that our similarity measure is a good indicator of relatedness of biological processes involved in causing the diseases. Although not needed for understanding this paper, the raw results are available for download for further study at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/DiseaseRelations/. PMID:25360770

Relating diseases by integrating gene associations and information flow through protein interaction network.

PubMed

Hamaneh, Mehdi Bagheri; Yu, Yi-Kuo

2014-01-01

Identifying similar diseases could potentially provide deeper understanding of their underlying causes, and may even hint at possible treatments. For this purpose, it is necessary to have a similarity measure that reflects the underpinning molecular interactions and biological pathways. We have thus devised a network-based measure that can partially fulfill this goal. Our method assigns weights to all proteins (and consequently their encoding genes) by using information flow from a disease to the protein interaction network and back. Similarity between two diseases is then defined as the cosine of the angle between their corresponding weight vectors. The proposed method also provides a way to suggest disease-pathway associations by using the weights assigned to the genes to perform enrichment analysis for each disease. By calculating pairwise similarities between 2534 diseases, we show that our disease similarity measure is strongly correlated with the probability of finding the diseases in the same disease family and, more importantly, sharing biological pathways. We have also compared our results to those of MimMiner, a text-mining method that assigns pairwise similarity scores to diseases. We find the results of the two methods to be complementary. It is also shown that clustering diseases based on their similarities and performing enrichment analysis for the cluster centers significantly increases the term association rate, suggesting that the cluster centers are better representatives for biological pathways than the diseases themselves. This lends support to the view that our similarity measure is a good indicator of relatedness of biological processes involved in causing the diseases. Although not needed for understanding this paper, the raw results are available for download for further study at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/DiseaseRelations/.

Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

PubMed

Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J

2016-01-01

Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest. CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store ( http://apps.cytoscape.org/apps/chat).

Direction Discovery: A Science Enrichment Program for High School Students

ERIC Educational Resources Information Center

Sikes, Suzanne S.; Schwartz-Bloom, Rochelle D.

2009-01-01

Launch into education about pharmacology (LEAP) is an inquiry-based science enrichment program designed to enhance competence in biology and chemistry and foster interest in science careers especially among under-represented minorities. The study of how drugs work, how they enter cells, alter body chemistry, and exit the body engages students to…

Gene-network inference by message passing

NASA Astrophysics Data System (ADS)

Braunstein, A.; Pagnani, A.; Weigt, M.; Zecchina, R.

2008-01-01

The inference of gene-regulatory processes from gene-expression data belongs to the major challenges of computational systems biology. Here we address the problem from a statistical-physics perspective and develop a message-passing algorithm which is able to infer sparse, directed and combinatorial regulatory mechanisms. Using the replica technique, the algorithmic performance can be characterized analytically for artificially generated data. The algorithm is applied to genome-wide expression data of baker's yeast under various environmental conditions. We find clear cases of combinatorial control, and enrichment in common functional annotations of regulated genes and their regulators.

Surficial geology along the Spokane River, Washington and its relationship to the metal content of sediments (Idaho-Washington stateline to Latah Creek confluence)

USGS Publications Warehouse

Box, Stephen E.; Wallis, John C.

2002-01-01

3. to compare the metal contents of different sedimentary lithologies. This data is used to gain some understanding of the physical and chemical processes that control those metal contents. It is hoped this study can be used to guide potential future remedial actions aimed at reducing the biologic impact of metal-enriched sediments in this area. This work was undertaken in cooperation with the Washington Department of Ecology and the Environmental Protection Agency.

Cardiolipin content is involved in liver mitochondrial energy wasting associated with cancer-induced cachexia without the involvement of adenine nucleotide translocase.

PubMed

Julienne, Cloé Mimsy; Tardieu, Marine; Chevalier, Stéphan; Pinault, Michelle; Bougnoux, Philippe; Labarthe, François; Couet, Charles; Servais, Stéphane; Dumas, Jean-François

2014-05-01

Cancer-induced cachexia describes the progressive skeletal muscle wasting associated with many cancers leading to shortened survival time in cancer patients. We previously reported that cardiolipin content and energy-wasting processes were both increased in liver mitochondria in a rat model of peritoneal carcinosis (PC)-induced cachexia. To increase the understanding of the cellular biology of cancer cachexia, we investigated the involvement of adenine nucleotide translocator (ANT) in mitochondrial energy-wasting processes in liver mitochondria of PC and pair-fed control rats and its interactions with cardiolipin in isolated liver mitochondria from healthy rats exposed to cardiolipin-enriched liposomes. We showed in this study that functional ANT content was decreased in liver mitochondria from PC rats but without any effects on the efficiency of ATP synthesis. Moreover, non-phosphorylating energy wasting was not affected by saturating concentrations of carboxyatractylate (CAT), a potent inhibitor of ANT, in liver mitochondria from PC rats. Decreased efficiency of ATP synthesis was found in normal liver mitochondria exposed to cardiolipin-enriched liposomes, with increased non-phosphorylating energy wasting, thus mimicking mitochondria from PC rats. However, the functional ANT content in these cardiolipin-enriched mitochondria was unchanged, although non-phosphorylating energy wasting was reduced by CAT-induced inhibition of ANT. Finally, non-phosphorylating energy wasting was increased in cardiolipin-enriched mitochondria with substrates for complexes 1 and 2, but not for complex 4. In conclusion, increased energy wasting measured in liver mitochondria from rats with cancer cachexia is dependent on cardiolipin but independent of ANT. Interactions between ANT and cardiolipin are modified when cancer cachexia occurs. Copyright © 2014 Elsevier B.V. All rights reserved.

Unique Physiological and Transcriptional Shifts under Combinations of Salinity, Drought, and Heat.

PubMed

Shaar-Moshe, Lidor; Blumwald, Eduardo; Peleg, Zvi

2017-05-01

Climate-change-driven stresses such as extreme temperatures, water deficit, and ion imbalance are projected to exacerbate and jeopardize global food security. Under field conditions, these stresses usually occur simultaneously and cause damages that exceed single stresses. Here, we investigated the transcriptional patterns and morpho-physiological acclimations of Brachypodium dystachion to single salinity, drought, and heat stresses, as well as their double and triple stress combinations. Hierarchical clustering analysis of morpho-physiological acclimations showed that several traits exhibited a gradually aggravating effect as plants were exposed to combined stresses. On the other hand, other morphological traits were dominated by salinity, while some physiological traits were shaped by heat stress. Response patterns of differentially expressed genes, under single and combined stresses (i.e. common stress genes), were maintained only among 37% of the genes, indicating a limited expression consistency among partially overlapping stresses. A comparison between common stress genes and genes that were uniquely expressed only under combined stresses (i.e. combination unique genes) revealed a significant shift from increased intensity to antagonistic responses, respectively. The different transcriptional signatures imply an alteration in the mode of action under combined stresses and limited ability to predict plant responses as different stresses are combined. Coexpression analysis coupled with enrichment analysis revealed that each gene subset was enriched with different biological processes. Common stress genes were enriched with known stress response pathways, while combination unique-genes were enriched with unique processes and genes with unknown functions that hold the potential to improve stress tolerance and enhance cereal productivity under suboptimal field conditions. © 2017 American Society of Plant Biologists. All Rights Reserved.

Where Do Epigenetics and Developmental Origins Take the Field of Developmental Psychopathology?

PubMed

Nigg, Joel T

2016-04-01

The time is ripe for upgrading or rethinking the assumed paradigms for how we study developmental psychopathology. The classic transactional models appear robust but need specification in terms of biological and psychosocial processes. That specification is increasingly tractable due to developments in genetics, epigenetics, the measurement of psychosocial processes, and theory and data on developmental origins of health and disease. This essay offers a high-level view of where the field has been and where it may be going in regard to nosology and conceptions of etiology. Remarks seek to consider rapidly evolving contexts not only for children, but also for the science itself due to progress in our field and in neighboring fields. Illustrations are provided as to how syndromal nosology can be enriched and advanced by careful integration with biologically relevant behavioral dimensions and application of quantitative methods. It is concluded that a revised, forward-looking, transactional model of abnormal child psychology will incorporate prenatal and postnatal developmental programming, epigenetic mechanisms and their associated genotype x environment interactions, and inflammatory processes as a potential common mediator influencing numerous health and mental health conditions.

Gene expression profile change and growth inhibition in Drosophila larvae treated with azadirachtin.

PubMed

Lai, Duo; Jin, Xiaoyong; Wang, Hao; Yuan, Mei; Xu, Hanhong

2014-09-20

Azadirachtin is a botanical insecticide that affects various biological processes. The effects of azadirachtin on the digital gene expression profile and growth inhibition in Drosophila larvae have not been investigated. In this study, we applied high-throughput sequencing technology to detect the differentially expressed genes of Drosophila larvae regulated by azadirachtin. A total of 15,322 genes were detected, and 28 genes were found to be significantly regulated by azadirachtin. Biological process and pathway analysis showed that azadirachtin affected starch and sucrose metabolism, defense response, signal transduction, instar larval or pupal development, and chemosensory behavior processes. The genes regulated by azadirachtin were mainly enriched in starch and sucrose metabolism. This study provided a general digital gene expression profile of dysregulated genes in response to azadirachtin and showed that azadirachtin provoked potent growth inhibitory effects in Drosophila larvae by regulating the genes of cuticular protein, amylase, and odorant-binding protein. Finally, we propose a potential mechanism underlying the dysregulation of the insulin/insulin-like growth factor signaling pathway by azadirachtin. Copyright © 2014 Elsevier B.V. All rights reserved.

Ca cycling and isotopic fluxes in forested ecosystems in Hawaii

USGS Publications Warehouse

Wiegand, B.A.; Chadwick, O.A.; Vitousek, P.M.; Wooden, J.L.

2005-01-01

Biogeochemical processes fractionate Ca isotopes in plants and soils along a 4 million year developmental sequence in the Hawaiian Islands. We observed that plants preferentially take up 40Ca relative to 44Ca, and that biological fractionation and changes in the relative contributions from volcanic and marine sources produce a significant increase in 44Ca in soil exchangeable pools. Our results imply moderate fluxes enriched in 44Ca from strongly nutrient-depleted old soils, in contrast with high 40Ca fluxes in young and little weathered environments. In addition, biological fractionation controls divergent geochemical pathways of Ca and Sr in the plant-soil system. While Ca depletes progressively with increasing soil age, Sr/Ca ratios increase systematically. Sr isotope ratios provide a valuable tracer for provenance studies of alkaline earth elements in forested ecosystems, but its usefulness is limited when deciphering biogeochemical processes involved in the terrestrial Ca cycle. Ca isotopes in combination with Sr/ Ca ratios reveal more complex processes involved in the biogeochemistry of Ca and Sr. Copyright 2005 by the American Geophysical Union.

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

PubMed

Yin, Li; Cai, Zhihui; Zhu, Baoan; Xu, Cunshuan

2018-02-14

Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC. Among the eight consecutive pathological stages, five representative modules are selected to perform canonical pathway enrichment and upstream regulator analysis by using ingenuity pathway analysis (IPA) software. We found that cell cycle related biological processes were activated at four neoplastic stages, and the degree of activation of the cell cycle corresponded to the deterioration degree of HCC. The orange and yellow modules enriched in energy metabolism, especially oxidative metabolism, and the expression value of the genes decreased only at four neoplastic stages. The brown module, enriched in protein ubiquitination and ephrin receptor signaling pathways, correlated mainly with the very early stage of HCC. The darkred module, enriched in hepatic fibrosis/hepatic stellate cell activation, correlated with the cirrhotic stage only. The high degree hub genes were identified based on the protein-protein interaction (PPI) network and were verified by Kaplan-Meier survival analysis. The novel five high degree hub genes signature that was identified in our study may shed light on future prognostic and therapeutic approaches. Our study brings a new perspective to the understanding of the key pathways and genes in the dynamic changes of HCC progression. These findings shed light on further investigations.

Whole exome sequencing implicates eye development, the unfolded protein response and plasma membrane homeostasis in primary open-angle glaucoma

PubMed Central

Souzeau, Emmanuelle; Sharma, Shiwani; Landers, John; Mills, Richard; Goldberg, Ivan; Healey, Paul R.; Graham, Stuart; Hewitt, Alex W.; Mackey, David A.; Galanopoulos, Anna; Casson, Robert J.; Ruddle, Jonathan B.; Ellis, Jonathan; Leo, Paul; Brown, Matthew A.; MacGregor, Stuart; Lynn, David J.; Burdon, Kathryn P.; Craig, Jamie E.

2017-01-01

Purpose To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants. Methods A total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF < 0.001) and potentially functionally damaging (nonsense, frameshift, splice or predicted pathogenic using SIFT or Polyphen2 software). Genes showing enrichment of qualifying variants in cases were selected for pathway and network analysis using InnateDB. Results POAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10–7, corrected p = 3.28×10–4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10–5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05×10–4, corrected p = 0.027) including calcium, chloride and phospholipid transporters involved in plasma membrane homeostasis. Network analysis also revealed enrichment of the MHC Class I antigen presentation pathway in HTG, and the EGFR1 and cell-cycle pathways in both HTG and NTG. Conclusion This study suggests that mutations in eye development genes are enriched in POAG. HTG can result from aberrant responses to protein misfolding which may be amenable to molecular chaperone therapy. NTG is associated with impaired plasma membrane homeostasis increasing susceptibility to apoptosis. PMID:28264060

CompGO: an R package for comparing and visualizing Gene Ontology enrichment differences between DNA binding experiments.

PubMed

Waardenberg, Ashley J; Basset, Samuel D; Bouveret, Romaric; Harvey, Richard P

2015-09-02

Gene ontology (GO) enrichment is commonly used for inferring biological meaning from systems biology experiments. However, determining differential GO and pathway enrichment between DNA-binding experiments or using the GO structure to classify experiments has received little attention. Herein, we present a bioinformatics tool, CompGO, for identifying Differentially Enriched Gene Ontologies, called DiEGOs, and pathways, through the use of a z-score derivation of log odds ratios, and visualizing these differences at GO and pathway level. Through public experimental data focused on the cardiac transcription factor NKX2-5, we illustrate the problems associated with comparing GO enrichments between experiments using a simple overlap approach. We have developed an R/Bioconductor package, CompGO, which implements a new statistic normally used in epidemiological studies for performing comparative GO analyses and visualizing comparisons from . BED data containing genomic coordinates as well as gene lists as inputs. We justify the statistic through inclusion of experimental data and compare to the commonly used overlap method. CompGO is freely available as a R/Bioconductor package enabling easy integration into existing pipelines and is available at: http://www.bioconductor.org/packages/release/bioc/html/CompGO.html packages/release/bioc/html/CompGO.html.

Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers

NASA Astrophysics Data System (ADS)

Cao, Weiqian; Huang, Jiangming; Jiang, Biyun; Gao, Xing; Yang, Pengyuan

2016-07-01

Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 μL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics.

Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers.

PubMed

Cao, Weiqian; Huang, Jiangming; Jiang, Biyun; Gao, Xing; Yang, Pengyuan

2016-07-14

Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 μL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics.

Proteomic profiling of maize opaque endosperm mutants reveals selective accumulation of lysine-enriched proteins

PubMed Central

Morton, Kyla J.; Jia, Shangang; Zhang, Chi; Holding, David R.

2016-01-01

Reduced prolamin (zein) accumulation and defective endoplasmic reticulum (ER) body formation occurs in maize opaque endosperm mutants opaque2 (o2), floury2 (fl2), defective endosperm*B30 (DeB30), and Mucronate (Mc), whereas other opaque mutants such as opaque1 (o1) and floury1 (fl1) are normal in these regards. This suggests that other factors contribute to kernel texture. A liquid chromatography approach coupled with tandem mass spectrometry (LC-MS/MS) proteomics was used to compare non-zein proteins of nearly isogenic opaque endosperm mutants. In total, 2762 proteins were identified that were enriched for biological processes such as protein transport and folding, amino acid biosynthesis, and proteolysis. Principal component analysis and pathway enrichment suggested that the mutants partitioned into three groups: (i) Mc, DeB30, fl2 and o2; (ii) o1; and (iii) fl1. Indicator species analysis revealed mutant-specific proteins, and highlighted ER secretory pathway components that were enriched in selected groups of mutants. The most significantly changed proteins were related to stress or defense and zein partitioning into the soluble fraction for Mc, DeB30, o1, and fl1 specifically. In silico dissection of the most significantly changed proteins revealed novel qualitative changes in lysine abundance contributing to the overall lysine increase and the nutritional rebalancing of the o2 and fl2 endosperm. PMID:26712829

Chemical Mapping of Proterozoic Organic Matter at Sub-Micron Spatial Resolution

NASA Technical Reports Server (NTRS)

Oehler, Dorothy Z.; Robert, Francois; Mostefaoui, Smail; Meibom, Anders; Selo, Madeleine; McKay, David S.

2006-01-01

We have used a NanoSIMS ion microprobe to map sub-micron-scale distributions of carbon, nitrogen, sulfur, silicon, and oxygen in organic microfossils and laminae from the approximately 0.85 Ga Bitter Springs Formation of Australia. The data provide clues about the original chemistry of the microfossils, the silicification process, and biosignatures of specific microorganisms and microbial communities. Chemical maps of fossil unicells and filaments reveal distinct wall-and sheath-like structures enriched in C, N and S, consistent with their accepted biological origin. Surprisingly, organic laminae, previously considered to be amorphous, also exhibit filamentous and apparently compressed spheroidal structures defined by strong enrichments in C, N and S. By analogy to data from the well-preserved microfossils, these structures are interpreted as being of biological origin, most likely representing densely packed remnants of microbial mats. Because the preponderance of organic matter in Precambrian sediments is similarly "amorphous," our findings open a large body of generally neglected material to in situ structural, chemical, and isotopic study. Our results also offer new criteria for assessing biogenicity of problematic kerogenous materials and thus can be applied to assessments of poorly preserved or fragmentary organic residues in early Archean sediments and any that might occur in meteorites or other extraterrestrial samples.

Systematic Analysis and Prediction of In Situ Cross Talk of O-GlcNAcylation and Phosphorylation

PubMed Central

Li, Ao; Wang, Minghui

2015-01-01

Reversible posttranslational modification (PTM) plays a very important role in biological process by changing properties of proteins. As many proteins are multiply modified by PTMs, cross talk of PTMs is becoming an intriguing topic and draws much attention. Currently, lots of evidences suggest that the PTMs work together to accomplish a specific biological function. However, both the general principles and underlying mechanism of PTM crosstalk are elusive. In this study, by using large-scale datasets we performed evolutionary conservation analysis, gene ontology enrichment, motif extraction of proteins with cross talk of O-GlcNAcylation and phosphorylation cooccurring on the same residue. We found that proteins with in situ O-GlcNAc/Phos cross talk were significantly enriched in some specific gene ontology terms and no obvious evolutionary pressure was observed. Moreover, 3 functional motifs associated with O-GlcNAc/Phos sites were extracted. We further used sequence features and GO features to predict O-GlcNAc/Phos cross talk sites based on phosphorylated sites and O-GlcNAcylated sites separately by the use of SVM model. The AUC of classifier based on phosphorylated sites is 0.896 and the other classifier based on GlcNAcylated sites is 0.843. Both classifiers achieved a relatively better performance compared with other existing methods. PMID:26601103

Systematic Analysis and Prediction of In Situ Cross Talk of O-GlcNAcylation and Phosphorylation.

PubMed

Yao, Heming; Li, Ao; Wang, Minghui

2015-01-01

Reversible posttranslational modification (PTM) plays a very important role in biological process by changing properties of proteins. As many proteins are multiply modified by PTMs, cross talk of PTMs is becoming an intriguing topic and draws much attention. Currently, lots of evidences suggest that the PTMs work together to accomplish a specific biological function. However, both the general principles and underlying mechanism of PTM crosstalk are elusive. In this study, by using large-scale datasets we performed evolutionary conservation analysis, gene ontology enrichment, motif extraction of proteins with cross talk of O-GlcNAcylation and phosphorylation cooccurring on the same residue. We found that proteins with in situ O-GlcNAc/Phos cross talk were significantly enriched in some specific gene ontology terms and no obvious evolutionary pressure was observed. Moreover, 3 functional motifs associated with O-GlcNAc/Phos sites were extracted. We further used sequence features and GO features to predict O-GlcNAc/Phos cross talk sites based on phosphorylated sites and O-GlcNAcylated sites separately by the use of SVM model. The AUC of classifier based on phosphorylated sites is 0.896 and the other classifier based on GlcNAcylated sites is 0.843. Both classifiers achieved a relatively better performance compared with other existing methods.

Fundamentals and Application of Magnetic Particles in Cell Isolation and Enrichment

PubMed Central

Plouffe, Brian D.; Murthy, Shashi K.; Lewis, Laura H.

2014-01-01

Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell separation systems. PMID:25471081

Combination of bioaugmentation and biostimulation for remediation of paddy soil contaminated with 2,4-dichlorophenoxyacetic acid.

PubMed

Yang, Zhiman; Xu, Xiaohui; Dai, Meng; Wang, Lin; Shi, Xiaoshuang; Guo, Rongbo

2018-04-22

The batch and fed-batch tests were performed to evaluate the efficiency of bioaugmentation in combination with biostimulation for remediation of paddy soil contaminated with 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D degrading enrichments were used for bioaugmentation, and effluents prepared through biological hydrogen production process were used as substrate for biostimulation. The batch tests indicated that 2,4-D degradation depended on the enrichment/substrate ratio (E/S), where E/S of 0.03 showed an excellent performance. The fed-batch tests showed that biostimulation only led to an improvement in 2,4-D degradation, while the pattern of repeated augmentation of enrichments (FRA) together with biostimulation obviously improved degradation of 2,4-D, 2-chlorophenol (2-CP) and phenol. DNA-sequencing approach showed that the FRA pattern altered the bacterial community composition, and high removal of 2,4-D, 2-CP and phenol may be attributed to the acclimation and persistence of Thauera. The findings demonstrated the importance of the FRA pattern on remediation of paddy soil contaminated with 2,4-D. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential Proteome Analysis of a Flor Yeast Strain under Biofilm Formation.

PubMed

Moreno-García, Jaime; Mauricio, Juan Carlos; Moreno, Juan; García-Martínez, Teresa

2017-03-28

Several Saccharomyces cerevisiae strains (flor yeasts) form a biofilm (flor velum) on the surface of Sherry wines after fermentation, when glucose is depleted. This flor velum is fundamental to biological aging of these particular wines. In this study, we identify abundant proteins in the formation of the biofilm of an industrial flor yeast strain. A database search to enrich flor yeast "biological process" and "cellular component" according to Gene Ontology Terminology (GO Terms) and, "pathways" was carried out. The most abundant proteins detected were largely involved in respiration, translation, stress damage prevention and repair, amino acid metabolism (glycine, isoleucine, leucine and arginine), glycolysis/gluconeogenesis and biosynthesis of vitamin B9 (folate). These proteins were located in cellular components as in the peroxisome, mitochondria, vacuole, cell wall and extracellular region; being these two last directly related with the flor formation. Proteins like Bgl2p, Gcv3p, Hyp2p, Mdh1p, Suc2p and Ygp1p were quantified in very high levels. This study reveals some expected processes and provides new and important information for the design of conditions and genetic constructions of flor yeasts for improving the cellular survival and, thus, to optimize biological aging of Sherry wine production.

A new method to track seed dispersal and recruitment using 15N isotope enrichment.

PubMed

Carlo, Tomás A; Tewksbury, Joshua J; Martínez Del Río, Carlos

2009-12-01

Seed dispersal has a powerful influence on population dynamics, genetic structuring, evolutionary rates, and community ecology. Yet, patterns of seed dispersal are difficult to measure due to methodological shortcomings in tracking dispersed seeds from sources of interest. Here we introduce a new method to track seed dispersal: stable isotope enrichment. It consists of leaf-feeding plants with sprays of 15N-urea during the flowering stage such that seeds developed after applications are isotopically enriched. We conducted a greenhouse experiment with Solanum americanum and two field experiments with wild Capsicum annuum in southern Arizona, USA, to field-validate the method. First, we show that plants sprayed with 15N-urea reliably produce isotopically enriched progeny, and that delta 15N (i.e., the isotopic ratio) of seeds and seedlings is a linear function of the 15N-urea concentration sprayed on mothers. We demonstrate that three urea dosages can be used to distinctly enrich plants and unambiguously differentiate their offspring after seeds are dispersed by birds. We found that, with high urea dosages, the resulting delta 15N values in seedlings are 10(3) - 10(4) times higher than the delta 15N values of normal plants. This feature allows tracking not only where seeds arrive, but in locations where seeds germinate and recruit, because delta 15N enrichment is detectable in seedlings that have increased in mass by at least two orders of magnitude before fading to normal delta 15N values. Last, we tested a mixing model to analyze seed samples in bulk. We used the delta 15N values of batches (i.e., combined seedlings or seeds captured in seed traps) to estimate the number of enriched seeds coming from isotopically enriched plants in the field. We confirm that isotope enrichment, combined with batch-sampling, is a cheap, reliable, and user-friendly method for bulk-processing seeds and is thus excellent for the detection of rare dispersal events. This method could further the study of dispersal biology, including the elusive, but critically important, estimation of long-distance seed dispersal.

Predicted Arabidopsis Interactome Resource and Gene Set Linkage Analysis: A Transcriptomic Analysis Resource.

PubMed

Yao, Heng; Wang, Xiaoxuan; Chen, Pengcheng; Hai, Ling; Jin, Kang; Yao, Lixia; Mao, Chuanzao; Chen, Xin

2018-05-01

An advanced functional understanding of omics data is important for elucidating the design logic of physiological processes in plants and effectively controlling desired traits in plants. We present the latest versions of the Predicted Arabidopsis Interactome Resource (PAIR) and of the gene set linkage analysis (GSLA) tool, which enable the interpretation of an observed transcriptomic change (differentially expressed genes [DEGs]) in Arabidopsis ( Arabidopsis thaliana ) with respect to its functional impact for biological processes. PAIR version 5.0 integrates functional association data between genes in multiple forms and infers 335,301 putative functional interactions. GSLA relies on this high-confidence inferred functional association network to expand our perception of the functional impacts of an observed transcriptomic change. GSLA then interprets the biological significance of the observed DEGs using established biological concepts (annotation terms), describing not only the DEGs themselves but also their potential functional impacts. This unique analytical capability can help researchers gain deeper insights into their experimental results and highlight prospective directions for further investigation. We demonstrate the utility of GSLA with two case studies in which GSLA uncovered how molecular events may have caused physiological changes through their collective functional influence on biological processes. Furthermore, we showed that typical annotation-enrichment tools were unable to produce similar insights to PAIR/GSLA. The PAIR version 5.0-inferred interactome and GSLA Web tool both can be accessed at http://public.synergylab.cn/pair/. © 2018 American Society of Plant Biologists. All Rights Reserved.

TOXICOKINETICS OF CHIRAL POLYCHLORINATED BIPHENYLS ACROSS DIFFERENT SPECIES—A REVIEW

PubMed Central

Kania-Korwel, Izabela; Lehmler, Hans-Joachim

2015-01-01

Nineteen PCBs (chiral or C-PCBs) exist as two stable rotational isomers (atropisomers) that are non-superimposable mirror images of each other. C-PCBs are released into the environment as racemic (i.e., equal) mixtures of both atropisomers and undergo atropisomeric enrichment due to biological, but not abiotic processes. In particular toxicokinetic studies provide important, initial insights into atropselective processes involved in the disposition (i.e., absorption, distribution, biotransformation and excretion) of C-PCBs. The toxicokinetic of C-PCBs is highly congener and species dependent. In particular at lower trophic levels, abiotic processes play a predominant role in C-PCB toxicokinetics. Biotransformation plays an important role in the elimination of C-PCBs in mammals. The elimination of C-PCB follows the approximate order mammals > birds > amphibians > fish, mostly due to a corresponding decrease in metabolic capacity. A few studies have shown differences in the toxicokinetics of C-PCB atropisomers; however, more work in needed to understand the toxicokinetics of C-PCBs and the underlying biological processes. Such studies will not only contribute to our understanding of the fate of C-PCBs in aquatic and terrestrial food webs, but also facilitate our understanding of human exposures to C-PCBs. PMID:25824003

Enhanced biological phosphorus removal with different carbon sources.

PubMed

Shen, Nan; Zhou, Yan

2016-06-01

Enhanced biological phosphorus removal (EBPR) process is one of the most economical and sustainable methods for phosphorus removal from wastewater. However, the performance of EBPR can be affected by available carbon sources types in the wastewater that may induce different functional microbial communities in the process. Glycogen accumulating organisms (GAOs) and polyphosphate accumulating organisms (PAOs) are commonly found by coexisting in the EBPR process. Predominance of GAO population may lead to EBPR failure due to the competition on carbon source with PAO without contributing phosphorus removal. Carbon sources indeed play an important role in alteration of PAOs and GAOs in EBPR processes. Various types of carbon sources have been investigated for EBPR performance. Certain carbon sources tend to enrich specific groups of GAOs and/or PAOs. This review summarizes the types of carbon sources applied in EBPR systems and highlights the roles of these carbon sources in PAO and GAO competition. Both single (e.g., acetate, propionate, glucose, ethanol, and amino acid) and complex carbon sources (e.g., yeast extract, peptone, and mixed carbon sources) are discussed in this review. Meanwhile, the environmental friendly and economical carbon sources that are derived from waste materials, such as crude glycerol and wasted sludge, are also discussed and compared.

Facile preparation of magnetic graphene double-sided mesoporous composites for the selective enrichment and analysis of endogenous peptides.

PubMed

Yin, Peng; Sun, Nianrong; Deng, Chunhui; Li, Yan; Zhang, Xiangmin; Yang, Pengyuan

2013-08-01

In this work, magnetic graphene double-sided mesoporous nanocomposites (mag-graphene@mSiO₂) were synthesized by coating a layer of mesoporous silica materials on each side of magnetic grapheme. The surfactant (CTAB) mediated sol-gel coating was performed using tetraethyl orthosilicate as the silica source. The as-made magnetic graphene double-sided mesoporous silica composites were treated with high-temperature calcination to remove the hydroxyl on the surface. The novel double-sided materials possess high surface area (167.8 cm²/g) and large pore volume (0.2 cm³/g). The highly open pore structure presents uniform pore size (3.2 nm) and structural stability. The hydrophobic interior pore walls could ensure an efficient adsorption of target molecules through hydrophobic-hydrophobic interaction. At the same time, the magnetic Fe₃O₄ particles on both sides of the materials could simplify the process of enrichment, which plays an important role in the treatment of complex biological samples. The magnetic graphene double-sided nanocomposites were successfully applied to size-selective and specific enrichment of peptides in standard peptide mixtures, protein digest solutions, and human urine samples. Finally, the novel material was applied to selective enrichment of endogenous peptides in mouse brain tissue. The enriched endogenous peptides were then analyzed by LC-MS/MS, and 409 endogenous peptides were detected and identified. The results demonstrate that the as-made mag-graphene@mSiO₂ have powerful potential for peptidome research. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.

PubMed

Ramanan, Vijay K; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L; Foroud, Tatiana M; Mukherjee, Shubhabrata; Crane, Paul K; Aisen, Paul S; Petersen, Ronald C; Weiner, Michael W; Saykin, Andrew J

2012-12-01

Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions.

PHYSICAL AND BIOLOGICAL CONTROLS ON DISSOLVED OXYGEN DYNAMICS IN PENSACOLA BAY, FL

EPA Science Inventory

Nutrient enrichment of estuaries and coastal waters can contribute to hypoxia (low dissolved oxygen) by increasing primary production and biological oxygen demand. Other factors, however, contribute to hypoxia and affect the susceptibility of coastal waters to hypoxia. Hypoxia fo...

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

PubMed

Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

2018-01-01

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease.

PubMed

Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni; Zhong, Wujuan; Konganti, Kranti; Abiodun-Ojo, Olayinka; Ness, Roberta B; O'Connell, Catherine M; Haggerty, Catherine L

2017-01-01

Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.

Identification of key microRNAs and genes in preeclampsia by bioinformatics analysis

PubMed Central

Luo, Shouling; Cao, Nannan; Tang, Yao; Gu, Weirong

2017-01-01

Preeclampsia is a leading cause of perinatal maternal–foetal mortality and morbidity. The aim of this study is to identify the key microRNAs and genes in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE84260 and the gene expression profile of GSE73374 from the Gene Expression Omnibus database. Differentially expressed miRNAs and genes were identified and compared to miRNA-target information from MiRWalk 2.0, and a total of 65 differentially expressed miRNAs (DEMIs), including 32 up-regulated miRNAs and 33 down-regulated miRNAs, and 91 differentially expressed genes (DEGs), including 83 up-regulated genes and 8 down-regulated genes, were identified. The pathway enrichment analyses of the DEMIs showed that the up-regulated DEMIs were enriched in the Hippo signalling pathway and MAPK signalling pathway, and the down-regulated DEMIs were enriched in HTLV-I infection and miRNAs in cancers. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses of the DEGs were performed using Multifaceted Analysis Tool for Human Transcriptome. The up-regulated DEGs were enriched in biological processes (BPs), including the response to cAMP, response to hydrogen peroxide and cell-cell adhesion mediated by integrin; no enrichment of down-regulated DEGs was identified. KEGG analysis showed that the up-regulated DEGs were enriched in the Hippo signalling pathway and pathways in cancer. A PPI network of the DEGs was constructed by using Cytoscape software, and FOS, STAT1, MMP14, ITGB1, VCAN, DUSP1, LDHA, MCL1, MET, and ZFP36 were identified as the hub genes. The current study illustrates a characteristic microRNA profile and gene profile in preeclampsia, which may contribute to the interpretation of the progression of preeclampsia and provide novel biomarkers and therapeutic targets for preeclampsia. PMID:28594854

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Genome-wide identification of runs of homozygosity islands and associated genes in local dairy cattle breeds.

PubMed

Mastrangelo, S; Sardina, M T; Tolone, M; Di Gerlando, R; Sutera, A M; Fontanesi, L; Portolano, B

2018-03-26

Runs of homozygosity (ROH) are widely used as predictors of whole-genome inbreeding levels in cattle. They identify regions that have an unfavorable effect on a phenotype when homozygous, but also identify the genes associated with traits of economic interest present in these regions. Here, the distribution of ROH islands and enriched genes within these regions in four dairy cattle breeds were investigated. Cinisara (71), Modicana (72), Reggiana (168) and Italian Holstein (96) individuals were genotyped using the 50K v2 Illumina BeadChip. The genomic regions most commonly associated with ROHs were identified by selecting the top 1% of the single nucleotide polymorphisms (SNPs) most commonly observed in the ROH of each breed. In total, 11 genomic regions were identified in Cinisara and Italian Holstein, and eight in Modicana and Reggiana, indicating an increased ROH frequency level. Generally, ROH islands differed between breeds. The most homozygous region (>45% of individuals with ROH) was found in Modicana on chromosome 6 within a quantitative trail locus affecting milk fat and protein concentrations. We identified between 126 and 347 genes within ROH islands, which are involved in multiple signaling and signal transduction pathways in a wide variety of biological processes. The gene ontology enrichment provided information on possible molecular functions, biological processes and cellular components under selection related to milk production, reproduction, immune response and resistance/susceptibility to infection and diseases. Thus, scanning the genome for ROH could be an alternative strategy to detect genomic regions and genes related to important economic traits.

Comparative Analysis of Transcriptomes of Macrophage Revealing the Mechanism of the Immunoregulatory Activities of a Novel Polysaccharide Isolated from Boletus speciosus Frost.

PubMed

Ding, Xiang; Zhu, Hongqing; Hou, Yiling; Hou, Wanru; Zhang, Nan; Fu, Lei

2017-01-01

The mechanism of the immunoregulatory activities of polysaccharide is still not clear. Here, we performed the B-cell, T-cell, and macrophage cell proliferation, the cell cycle analysis of macrophage cells, sequenced the transcriptomes of control group macrophages, and Boletus speciosus Frost polysaccharide (BSF-1) group macrophages using Illumina sequencing technology to identify differentially expressed genes (DEGs) to determine the molecular mechanisms of immunomodulatory activity of BSF-1 in macrophages. These results suggested that BSF-1 could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell division. A total of 12,498,414 and 11,840,624 bp paired-end reads were obtained for the control group and BSF-1 group, respectively, and they corresponded to a total size of 12.5 G bp and 11.8 G bp, respectively, after the low-quality reads and adapter sequences were removed. Approximately 81.83% of the total number of genes (8,257) were expressed reads per kilobase per million mapped reads (RPKM ≥1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 group. A gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functions. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathways are significantly enriched for DEGs between the two cell groups. An analysis of transcriptome resources enabled us to examine gene expression profiles, verify differential gene expression, and select candidate signaling pathways as the mechanisms of the immunomodulatory activity of BSF-1. Based on the experimental data, we believe that the significant antitumor activities of BSF-1 in vivo mainly involve the MAPK signaling pathways. Boletus speciosus Frost-1 (BSF-1) could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell divisionApproximately 81.83% of the total number of genes (8257) were expressed (reads per kilobase per million mapped reads [RPKM] =1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 groupA gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functionsA Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase signaling pathways are significantly enriched for DEGs between the two cell groups. Abbreviations used: BSF-1: Boletus speciosus Frost polysaccharide.

Proteomic Profiling of De Novo Protein Synthesis in Starvation-Induced Autophagy Using Bioorthogonal Noncanonical Amino Acid Tagging.

PubMed

Zhang, J; Wang, J; Lee, Y-M; Lim, T-K; Lin, Q; Shen, H-M

2017-01-01

Autophagy is an intracellular degradation process activated by stress factors such as nutrient starvation to maintain cellular homeostasis. There is emerging evidence demonstrating that de novo protein synthesis is involved in the autophagic process. However, up-to-date characterizing of these de novo proteins is technically difficult. In this chapter, we describe a novel method to identify newly synthesized proteins during starvation-mediated autophagy by bioorthogonal noncanonical amino acid tagging (BONCAT), in conjunction with isobaric tagging for relative and absolute quantification (iTRAQ)-based quantitative proteomics. l-azidohomoalanine (AHA) is an analog of methionine, and it can be readily incorporated into the newly synthesized proteins. The AHA-containing proteins can be enriched with avidin beads after a "click" reaction between alkyne-bearing biotin and the azide moiety of AHA. The enriched proteins are then subjected to iTRAQ™ labeling for protein identification and quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). By using this technique, we have successfully profiled more than 700 proteins that are synthesized during starvation-induced autophagy. We believe that this approach is effective in identification of newly synthesized proteins in the process of autophagy and provides useful insights to the molecular mechanisms and biological functions of autophagy. © 2017 Elsevier Inc. All rights reserved.

Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in Aspergillus flavus*

PubMed Central

Ren, Silin; Yang, Mingkun; Yue, Yuewei; Ge, Feng; Li, Yu; Guo, Xiaodong; Zhang, Jia; Zhang, Feng; Nie, Xinyi; Wang, Shihua

2018-01-01

Aspergillus flavus (A. flavus) is a ubiquitous saprophytic and pathogenic fungus that produces the aflatoxin carcinogen, and A. flavus can have tremendous economic and health impacts worldwide. Increasing evidence demonstrates that lysine succinylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine succinylation in A. flavus. Here, we performed a global succinylome analysis of A. flavus using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 985 succinylation sites on 349 succinylated proteins were identified in this pathogen. Bioinformatics analysis revealed that the succinylated proteins were involved in various biological processes and were particularly enriched in the aflatoxin biosynthesis process. Site-specific mutagenesis and biochemical studies showed that lysine succinylation on the norsolorinic acid reductase NorA (AflE), a key enzyme in aflatoxins biosynthesis, can affect the production of sclerotia and aflatoxins biosynthesis in A. flavus. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and aflatoxins biosynthesis in A. flavus. Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this pathogen. PMID:29298838

Proteomic analysis of Bombyx mori molting fluid: Insights into the molting process.

PubMed

Liu, Hua-Wei; Wang, Luo-Ling; Tang, Xin; Dong, Zhao-Ming; Guo, Peng-Chao; Zhao, Dong-Chao; Xia, Qing-You; Zhao, Ping

2018-02-20

Molting is an essential biological process occurring multiple times throughout the life cycle of most Ecdysozoa. Molting fluids accumulate and function in the exuvial space during the molting process. In this study, we used liquid chromatography-tandem mass spectrometry to investigate the molting fluids to analyze the molecular mechanisms of molting in the silkworm, Bombyx mori. In total, 375 proteins were identified in molting fluids from the silkworm at 14-16h before pupation and eclosion, including 12 chitin metabolism-related enzymes, 35 serine proteases, 15 peptidases, and 38 protease inhibitors. Gene ontology analysis indicated that "catalytic" constitutes the most enriched function in the molting fluid. Gene expression patterns and bioinformatic analyses suggested that numerous enzymes are involved in the degradation of cuticle proteins and chitin. Protein-protein interaction network and activity analyses showed that protease inhibitors are involved in the regulation of multiple pathways in molting fluid. Additionally, many immune-related proteins may be involved in the immune defense during molting. These results provide a comprehensive proteomic insight into proteolytic enzymes and protease inhibitors in molting fluid, and will likely improve the current understanding of physiological processes in insect molting. Insect molting constitutes a dynamic physiological process. To better understand this process, we used LC-MS/MS to investigate the proteome of silkworm molting fluids and identified key proteins involved in silkworm molting. The biological processes of the old cuticle degradation pathway and immune defense response were analyzed in the proteome of silkworm molting fluid. We report that protease inhibitors serve as key factors in the regulation of the molting process. The proteomic results provide new insight into biological molting processes in insects. Copyright © 2017 Elsevier B.V. All rights reserved.

The use of selective adsorbents in capillary electrophoresis-mass spectrometry for analyte preconcentration and microreactions: a powerful three-dimensional tool for multiple chemical and biological applications.

PubMed

Guzman, N A; Stubbs, R J

2001-10-01

Much attention has recently been directed to the development and application of online sample preconcentration and microreactions in capillary electrophoresis using selective adsorbents based on chemical or biological specificity. The basic principle involves two interacting chemical or biological systems with high selectivity and affinity for each other. These molecular interactions in nature usually involve noncovalent and reversible chemical processes. Properly bound to a solid support, an "affinity ligand" can selectively adsorb a "target analyte" found in a simple or complex mixture at a wide range of concentrations. As a result, the isolated analyte is enriched and highly purified. When this affinity technique, allowing noncovalent chemical interactions and biochemical reactions to occur, is coupled on-line to high-resolution capillary electrophoresis and mass spectrometry, a powerful tool of chemical and biological information is created. This paper describes the concept of biological recognition and affinity interaction on-line with high-resolution separation, the fabrication of an "analyte concentrator-microreactor", optimization conditions of adsorption and desorption, the coupling to mass spectrometry, and various applications of clinical and pharmaceutical interest.

Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.

PubMed

Zhang, Jing; Koch, Iris; Gibson, Laura A; Loughery, Jennifer R; Martyniuk, Christopher J; Button, Mark; Caumette, Guilhem; Reimer, Kenneth J; Cullen, William R; Langlois, Valerie S

2015-12-01

Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Identification of OBO nonalignments and its implications for OBO enrichment.

PubMed

Bada, Michael; Hunter, Lawrence

2008-06-15

Existing projects that focus on the semiautomatic addition of links between existing terms in the Open Biomedical Ontologies can take advantage of reasoners that can make new inferences between terms that are based on the added formal definitions and that reflect nonalignments between the linked terms. However, these projects require that these definitions be necessary and sufficient, a strong requirement that often does not hold. If such definitions cannot be added, the reasoners cannot point to the nonalignments through the suggestion of new inferences. We describe a methodology by which we have identified over 1900 instances of nonredundant nonalignments between terms from the Gene Ontology (GO) biological process (BP), cellular component (CC) and molecular function (MF) ontologies, Chemical Entities of Biological Interest (ChEBI) and the Cell Type Ontology (CL). Many of the 39.8% of these nonalignments whose object terms are more atomic than the subject terms are not currently examined in other ontology-enrichment projects due to the fact that the necessary and sufficient conditions required for the inferences are not currently examined. Analysis of the ratios of nonalignments to assertions from which the nonalignments were identified suggests that BP-MF, BP-BP, BP-CL and CC-CC terms are relatively well-aligned, while ChEBI-MF, BP-ChEBI and CC-MF terms are relatively not aligned well. We propose four ways to resolve an identified nonalignment and recommend an analogous implementation of our methodology in ontology-enrichment tools to identify types of nonalignments that are currently not detected. The nonalignments discussed in this article may be viewed at http://compbio.uchsc.edu/Hunter_lab/Bada/nonalignments_2008_03_06.html. Code for the generation of these nonalignments is available upon request. mike.bada@uchsc.edu.

Relationship of Hydrogen Bioavailability to Chromate Reduction in Aquifer Sediments

PubMed Central

Marsh, Tamara L.; McInerney, Michael J.

2001-01-01

Biological Cr(VI) reduction was studied in anaerobic sediments from an aquifer in Norman, Okla. Microcosms containing sediment and mineral medium were amended with various electron donors to determine those most important for biological Cr(VI) reduction. Cr(VI) (about 340 μM) was reduced with endogenous substrates (no donor), or acetate was added. The addition of formate, hydrogen, and glucose stimulated Cr(VI) reduction compared with reduction in unamended controls. From these sediments, an anaerobic Cr(VI)-utilizing enrichment was obtained that was dependent upon hydrogen for both growth and Cr(VI) reduction. No methane was produced by the enrichment, which reduced about 750 μM Cr(VI) in less than six days. The dissolved hydrogen concentration was used as an indicator of the terminal electron accepting process occurring in the sediments. Microcosms with sediments, groundwater, and chromate metabolized hydrogen to a concentration below the detection limits of the mercury vapor gas chromatograph. In microcosms without chromate, the hydrogen concentration was about 8 nM, a concentration comparable to that under methanogenic conditions. When these microcosms were amended with 500 μM Cr(VI), the dissolved hydrogen concentration quickly fell below the detection limits. These results showed that the hydrogen concentration under chromate-reducing conditions became very low, as low as that reported under nitrate- and manganese-reducing conditions, a result consistent with the free energy changes for these reactions. The utilization of formate, lactate, hydrogen, and glucose as electron donors for Cr(VI) reduction indicates that increasing the availability of hydrogen results in a greater capacity for Cr(VI) reduction. This conclusion is supported by the existence of an enrichment dependent upon hydrogen for growth and Cr(VI) reduction. PMID:11282599

The Role of Management in Enrichment Ratio Dynamics and Resilience of Aggregate Fractions Via Raindrop Impact within Agricultural Hillslopes

NASA Astrophysics Data System (ADS)

Wacha, K.; Papanicolaou, T.; Hatfield, J.; Cambardella, C.; Abban, B. K.; Wilson, C. G.; Filley, T. R.; Hou, T.; Dold, C.

2017-12-01

The abundance and distribution of surface soil size fractions has been shown to be reflective of changes in management practices and landscape position. Soil size fractions exist in both un-aggregated and aggregated forms that differ in textural and biological composition, which can impact soil hydrology and aggregation processes. Soils with higher stocks of soil organic matter (SOM) promote higher biological activity, infiltration, and soil structure due to stronger, more resilient aggregates. Within ag-systems, intensive cultivation and steep gradients can negatively impact the formation/stability of aggregates and amplify erosion processes, which redistributes material along downslope flowpathways to varying degrees, based on the amount of available surface cover during a rainfall event. The innate variability in SOM composition found amongst the size fractions combined with these highly active flowpathways, produces a symphony of interactive biogeochemical and hydrologic processes, which promote spatial landscape heterogeneity. Due to this intricacy, accurately assessing changes in SOM stocks within high energy ag-systems is extremely challenging, and could greatly impact soil carbon budgets at the hillslope and greater spatial scales. To address this, in part, we utilize a systematic approach that isolates the role of management in building aggregate resilience to hydrologic forcing. Soil samples were collected from farm fields with varying slopes (1-20%) and management conditions, and then isolated into seven aggregate size fractions. Each aggregate fraction was tested for resilience to raindrop impact with corresponding SOM composition and biological activity. Rainfall simulations were conducted on plots under representative management and gradient to capture the dynamicity of the size fractions being transported during an applied rainfall event. Results found that small macroaggregate fractions were most indicative of changes in management, and erosion rates from plots were inversely proportional to SOM enrichment. These experiments not only promote our fundamental understanding on the dynamics of surface soil and SOM redistribution but also can provide guidance into best management practices that promote aggregate stability, decrease soil loss, and enhance soil health.

Network biology discovers pathogen contact points in host protein-protein interactomes.

PubMed

Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

2018-06-13

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

``Recycling'' Geophysics: Monitoring and Isotopic Analysis of Engineered Biological Systems

NASA Astrophysics Data System (ADS)

Doherty, R.; Singh, K. P.; Ogle, N.; Ntarlagiannis, D.

2010-12-01

The emerging sub discipline of biogeophysics has provoked debate on the mechanisms of microbial processes that may contribute to geophysical signatures. At field scales geophysical signatures are often non unique due to the many parameters (physical, chemical, and biological) that are involved. It may be easier to apply geophysical techniques such as electrodic potential (EP), self potential (SP) and induced polarization (IP) to engineered biological systems where there is a degree of control over the design of the physical and chemical domain. Here we present results of a column experiment that was designed to anaerobically biodegrade dissolved organic matter in landfill leachate. The column utilises a recycled porous media (concrete) to help sequester organic carbon. Electrodic potential, self potential and induced polarisation are used in conjunction with chemical and isotopic techniques to monitor the effectiveness of this approach. Preliminary carbon and oxygen isotopic analysis on concrete from the column in contact with leachate show isotopic enrichment suggesting abiotic precipitation of carbonates.

Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.

PubMed

Guo, Michael; Liu, Zun; Willen, Jessie; Shaw, Cameron P; Richard, Daniel; Jagoda, Evelyn; Doxey, Andrew C; Hirschhorn, Joel; Capellini, Terence D

2017-12-05

GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at CHSY1 , we identified a candidate causal variant (rs9920291) overlapping an open chromatin region. Reporter assays demonstrated that rs9920291 shows allelic regulatory activity, and CRISPR/Cas9 targeting of human chondrocytes demonstrates that the region regulates CHSY1 expression. Thus, integrating biologically relevant epigenetic information (here, from growth plates) with genetic association results can identify biological mechanisms important for human growth.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides

NASA Astrophysics Data System (ADS)

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-01

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05955g

Enrichment of glioma stem cell-like cells on 3D porous scaffolds composed of different extracellular matrix.

PubMed

Wang, Xuanzhi; Dai, Xingliang; Zhang, Xinzhi; Li, Xinda; Xu, Tao; Lan, Qing

2018-04-15

Cancer stem cells (CSCs), being tumor-initiating with self-renewal capacity and heterogeneity, are most likely the cause of tumor resistance, reoccurrence and metastasis. To further investigate the role of CSCs in tumor biology, there is a need to develop an effective culture system to grow, maintain and enrich CSCs. Three-dimensional (3D) cell culture model has been widely used in tumor research and drug screening. Recently, researchers have begun to utilize 3D models to culture cancer cells for CSCs enrichment. In this study, glioma cell line was cultured with 3D porous chitosan (CS) scaffolds or chitosan-hyaluronic acid (CS-HA) scaffolds to explore the possibility of glioma stem cells (GSCs)-like cells enrichment, to study the morphology, gene expression, and in vivo tumorigenicity of 3D scaffolds cells, and to compare results to 2D controls. Results showed that glioma cells on both CS and CS-HA scaffolds could form tumor cell spheroids and increased the expression of GSCs biomarkers compared to conventional 2D monolayers. Furthermore, cells in CS-HA scaffolds had higher expression levels of epithelial-to-mesenchymal transition (EMT)-related gene. Specifically, the in vivo tumorigenicity capability of CS-HA scaffold cultured cells was greater than 2D cells or CS scaffold cultured cells. It is indicated that the chemical composition of scaffold plays an important role in the enrichment of CSCs. Our results suggest that CS-HA scaffolds have a better capability to enrich GSCs-like cells and can serve as a simple and effective way to cultivate and enrich CSCs in vitro to support the study of CSCs biology and development of novel anti-cancer therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

16. VIEW OF THE ENRICHED URANIUM RECOVERY SYSTEM. ENRICHED URANIUM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. VIEW OF THE ENRICHED URANIUM RECOVERY SYSTEM. ENRICHED URANIUM RECOVERY PROCESSED RELATIVELY PURE MATERIALS AND SOLUTIONS AND SOLID RESIDUES WITH RELATIVELY LOW URANIUM CONTENT. URANIUM RECOVERY INVOLVED BOTH SLOW AND FAST PROCESSES. (4/4/66) - Rocky Flats Plant, General Manufacturing, Support, Records-Central Computing, Southern portion of Plant, Golden, Jefferson County, CO

GeLC-MRM quantitation of mutant KRAS oncoprotein in complex biological samples.

PubMed

Halvey, Patrick J; Ferrone, Cristina R; Liebler, Daniel C

2012-07-06

Tumor-derived mutant KRAS (v-Ki-ras-2 Kirsten rat sarcoma viral oncogene) oncoprotein is a critical driver of cancer phenotypes and a potential biomarker for many epithelial cancers. Targeted mass spectrometry analysis by multiple reaction monitoring (MRM) enables selective detection and quantitation of wild-type and mutant KRAS proteins in complex biological samples. A recently described immunoprecipitation approach (Proc. Nat. Acad. Sci.2011, 108, 2444-2449) can be used to enrich KRAS for MRM analysis, but requires large protein inputs (2-4 mg). Here, we describe sodium dodecyl sulfate-polyacrylamide gel electrophoresis-based enrichment of KRAS in a low molecular weight (20-25 kDa) protein fraction prior to MRM analysis (GeLC-MRM). This approach reduces background proteome complexity, thus, allowing mutant KRAS to be reliably quantified in low protein inputs (5-50 μg). GeLC-MRM detected KRAS mutant variants (G12D, G13D, G12V, G12S) in a panel of cancer cell lines. GeLC-MRM analysis of wild-type and mutant was linear with respect to protein input and showed low variability across process replicates (CV = 14%). Concomitant analysis of a peptide from the highly similar HRAS and NRAS proteins enabled correction of KRAS-targeted measurements for contributions from these other proteins. KRAS peptides were also quantified in fluid from benign pancreatic cysts and pancreatic cancers at concentrations from 0.08 to 1.1 fmol/μg protein. GeLC-MRM provides a robust, sensitive approach to quantitation of mutant proteins in complex biological samples.

Small RNAs as important regulators for the hybrid vigour of super-hybrid rice.

PubMed

Zhang, Lei; Peng, Yonggang; Wei, Xiaoli; Dai, Yan; Yuan, Dawei; Lu, Yufei; Pan, Yangyang; Zhu, Zhen

2014-11-01

Heterosis is an important biological phenomenon; however, the role of small RNA (sRNA) in heterosis of hybrid rice remains poorly described. Here, we performed sRNA profiling of F1 super-hybrid rice LYP9 and its parents using high-throughput sequencing technology, and identified 355 distinct mature microRNAs and trans-acting small interfering RNAs, 69 of which were differentially expressed sRNAs (DES) between the hybrid and the mid-parental value. Among these, 34 DES were predicted to target 176 transcripts, of which 112 encoded 94 transcription factors. Further analysis showed that 67.6% of DES expression levels were negatively correlated with their target mRNAs either in flag leaves or panicles. The target genes of DES were significantly enriched in some important biological processes, including the auxin signalling pathway, in which existed a regulatory network mediated by DES and their targets, closely associated with plant growth and development. Overall, 20.8% of DES and their target genes were significantly enriched in quantitative trait loci of small intervals related to important rice agronomic traits including growth vigour, grain yield, and plant architecture, suggesting that the interaction between sRNAs and their targets contributes to the heterotic phenotypes of hybrid rice. Our findings revealed that sRNAs might play important roles in hybrid vigour of super-hybrid rice by regulating their target genes, especially in controlling the auxin signalling pathway. The above finding provides a novel insight into the molecular mechanism of heterosis. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Factors that predict consumer acceptance of enriched processed meats.

PubMed

Shan, Liran C; Henchion, Maeve; De Brún, Aoife; Murrin, Celine; Wall, Patrick G; Monahan, Frank J

2017-11-01

The study aimed to understand predictors of consumers' purchase intention towards processed meat based functional foods (i.e. enriched processed meat). A cross-sectional survey was conducted with 486 processed meat consumers in spring 2016. Results showed that processed meats were perceived differently in healthiness, with sausage-type products perceived less healthy than cured meat products. Consumers were in general more uncertain than positive about enriched processed meat but differences existed in terms of the attitudes and purchase intention. Following regression analysis, consumers' purchase intention towards enriched processed meat was primarily driven by their attitudes towards the product concept. Perceived healthiness of existing products and eating frequency of processed meat were also positively associated with the purchase intention. Other factors such as general food choice motives, socio-demographic characteristics, consumer health and the consumption of functional foods and dietary supplements in general, were not significant predictors of the purchase intention for enriched processed meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Characteristics of heavy metals enrichment in algae ano its application prospects].

PubMed

Lu, Kaixing; Tang, Jian-jun; Jiang, De'an

2006-01-01

Using algae to bio-remedy heavy metals-contaminated waters has become an available and practical approach for environmental restoration. Because of its special cell wall structure, high capacity of heavy metal-enrichment, and easy to desorption, algae has been considered as an ideal biological adsorbent. This paper briefly introduced the structural and metabolic characteristics adapted for heavy metals enrichment of algae, including functional groups on cell wall, extracellular products, and intracellular heavy metals-chelating proteins, discussed the enrichment capability of living, dead and immobilized algae as well as the simple and convenient ways for desorption, and analyzed the advantages and disadvantages of using algae for bioremediation of polluted water, and its application prospects.

Determining Semantically Related Significant Genes.

PubMed

Taha, Kamal

2014-01-01

GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

Fungal Genes in Context: Genome Architecture Reflects Regulatory Complexity and Function

PubMed Central

Noble, Luke M.; Andrianopoulos, Alex

2013-01-01

Gene context determines gene expression, with local chromosomal environment most influential. Comparative genomic analysis is often limited in scope to conserved or divergent gene and protein families, and fungi are well suited to this approach with low functional redundancy and relatively streamlined genomes. We show here that one aspect of gene context, the amount of potential upstream regulatory sequence maintained through evolution, is highly predictive of both molecular function and biological process in diverse fungi. Orthologs with large upstream intergenic regions (UIRs) are strongly enriched in information processing functions, such as signal transduction and sequence-specific DNA binding, and, in the genus Aspergillus, include the majority of experimentally studied, high-level developmental and metabolic transcriptional regulators. Many uncharacterized genes are also present in this class and, by implication, may be of similar importance. Large intergenic regions also share two novel sequence characteristics, currently of unknown significance: they are enriched for plus-strand polypyrimidine tracts and an information-rich, putative regulatory motif that was present in the last common ancestor of the Pezizomycotina. Systematic consideration of gene UIR in comparative genomics, particularly for poorly characterized species, could help reveal organisms’ regulatory priorities. PMID:23699226

Systematic identification of latent disease-gene associations from PubMed articles.

PubMed

Zhang, Yuji; Shen, Feichen; Mojarad, Majid Rastegar; Li, Dingcheng; Liu, Sijia; Tao, Cui; Yu, Yue; Liu, Hongfang

2018-01-01

Recent scientific advances have accumulated a tremendous amount of biomedical knowledge providing novel insights into the relationship between molecular and cellular processes and diseases. Literature mining is one of the commonly used methods to retrieve and extract information from scientific publications for understanding these associations. However, due to large data volume and complicated associations with noises, the interpretability of such association data for semantic knowledge discovery is challenging. In this study, we describe an integrative computational framework aiming to expedite the discovery of latent disease mechanisms by dissecting 146,245 disease-gene associations from over 25 million of PubMed indexed articles. We take advantage of both Latent Dirichlet Allocation (LDA) modeling and network-based analysis for their capabilities of detecting latent associations and reducing noises for large volume data respectively. Our results demonstrate that (1) the LDA-based modeling is able to group similar diseases into disease topics; (2) the disease-specific association networks follow the scale-free network property; (3) certain subnetwork patterns were enriched in the disease-specific association networks; and (4) genes were enriched in topic-specific biological processes. Our approach offers promising opportunities for latent disease-gene knowledge discovery in biomedical research.

Systematic identification of latent disease-gene associations from PubMed articles

PubMed Central

Mojarad, Majid Rastegar; Li, Dingcheng; Liu, Sijia; Tao, Cui; Yu, Yue; Liu, Hongfang

2018-01-01

Recent scientific advances have accumulated a tremendous amount of biomedical knowledge providing novel insights into the relationship between molecular and cellular processes and diseases. Literature mining is one of the commonly used methods to retrieve and extract information from scientific publications for understanding these associations. However, due to large data volume and complicated associations with noises, the interpretability of such association data for semantic knowledge discovery is challenging. In this study, we describe an integrative computational framework aiming to expedite the discovery of latent disease mechanisms by dissecting 146,245 disease-gene associations from over 25 million of PubMed indexed articles. We take advantage of both Latent Dirichlet Allocation (LDA) modeling and network-based analysis for their capabilities of detecting latent associations and reducing noises for large volume data respectively. Our results demonstrate that (1) the LDA-based modeling is able to group similar diseases into disease topics; (2) the disease-specific association networks follow the scale-free network property; (3) certain subnetwork patterns were enriched in the disease-specific association networks; and (4) genes were enriched in topic-specific biological processes. Our approach offers promising opportunities for latent disease-gene knowledge discovery in biomedical research. PMID:29373609

Robotic Enrichment Processing of Roche 454 Titanium Emlusion PCR at the DOE Joint Genome Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Matthew; Wilson, Steven; Bauer, Diane

2010-05-28

Enrichment of emulsion PCR product is the most laborious and pipette-intensive step in the 454 Titanium process, posing the biggest obstacle for production-oriented scale up. The Joint Genome Institute has developed a pair of custom-made robots based on the Microlab Star liquid handling deck manufactured by Hamilton to mediate the complexity and ergonomic demands of the 454 enrichment process. The robot includes a custom built centrifuge, magnetic deck positions, as well as heating and cooling elements. At present processing eight emulsion cup samples in a single 2.5 hour run, these robots are capable of processing up to 24 emulsion cupmore » samples. Sample emulsions are broken using the standard 454 breaking process and transferred from a pair of 50ml conical tubes to a single 2ml tube and loaded on the robot. The robot performs the enrichment protocol and produces beads in 2ml tubes ready for counting. The robot follows the Roche 454 enrichment protocol with slight exceptions to the manner in which it resuspends beads via pipette mixing rather than vortexing and a set number of null bead removal washes. The robotic process is broken down in similar discrete steps: First Melt and Neutralization, Enrichment Primer Annealing, Enrichment Bead Incubation, Null Bead Removal, Second Melt and Neutralization and Sequencing Primer Annealing. Data indicating our improvements in enrichment efficiency and total number of bases per run will also be shown.« less

Text-based Analytics for Biosurveillance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charles, Lauren E.; Smith, William P.; Rounds, Jeremiah

The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related tomore » biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when). The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related to biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when).« less

Genes and pathways co-associated with the exposure to multiple drugs of abuse, including alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine, and/or nicotine: a review of proteomics analyses.

PubMed

Wang, Ju; Yuan, Wenji; Li, Ming D

2011-12-01

Drug addiction is a chronic neuronal disease. In recent years, proteomics technology has been widely used to assess the protein expression in the brain tissues of both animals and humans exposed to addictive drugs. Through this approach, a large number of proteins potentially involved in the etiology of drug addictions have been identified, which provide a valuable resource to study protein function, biochemical pathways, and networks related to the molecular mechanisms underlying drug dependence. In this article, we summarize the recent application of proteomics to profiling protein expression patterns in animal or human brain tissues after the administration of alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine/heroin/butorphanol, or nicotine. From available reports, we compiled a list of 497 proteins associated with exposure to one or more addictive drugs, with 160 being related to exposure to at least two abused drugs. A number of biochemical pathways and biological processes appear to be enriched among these proteins, including synaptic transmission and signaling pathways related to neuronal functions. The data included in this work provide a summary and extension of the proteomics studies on drug addiction. Furthermore, the proteins and biological processes highlighted here may provide valuable insight into the cellular activities and biological processes in neurons in the development of drug addiction.

T-cell lymphomas associated gene expression signature: Bioinformatics analysis based on gene expression Omnibus.

PubMed

Zhou, Lei-Lei; Xu, Xiao-Yue; Ni, Jie; Zhao, Xia; Zhou, Jian-Wei; Feng, Ji-Feng

2018-06-01

Due to the low incidence and the heterogeneity of subtypes, the biological process of T-cell lymphomas is largely unknown. Although many genes have been detected in T-cell lymphomas, the role of these genes in biological process of T-cell lymphomas was not further analyzed. Two qualified datasets were downloaded from Gene Expression Omnibus database. The biological functions of differentially expressed genes were evaluated by gene ontology enrichment and KEGG pathway analysis. The network for intersection genes was constructed by the cytoscape v3.0 software. Kaplan-Meier survival curves and log-rank test were employed to assess the association between differentially expressed genes and clinical characters. The intersection mRNAs were proved to be associated with fundamental processes of T-cell lymphoma cells. These intersection mRNAs were involved in the activation of some cancer-related pathways, including PI3K/AKT, Ras, JAK-STAT, and NF-kappa B signaling pathway. PDGFRA, CXCL12, and CCL19 were the most significant central genes in the signal-net analysis. The results of survival analysis are not entirely credible. Our findings uncovered aberrantly expressed genes and a complex RNA signal network in T-cell lymphomas and indicated cancer-related pathways involved in disease initiation and progression, providing a new insight for biotargeted therapy in T-cell lymphomas. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptomic variation of eyestalk reveals the genes and biological processes associated with molting in Portunus trituberculatus

PubMed Central

Zhang, Longtao; Liu, Ping; Li, Jian

2017-01-01

Background Molting is an essential biological process throughout the life history of crustaceans, which is regulated by many neuropeptide hormones expressed in the eyestalk. To better understand the molting mechanism in Portunus trituberculatus, we used digital gene expression (DGE) to analyze single eyestalk samples during the molting cycle by high-throughput sequencing. Results We obtained 14,387,942, 12,631,508 and 13,060,062 clean sequence reads from inter-molt (InM), pre-molt (PrM) and post-molt (PoM) cDNA libraries, respectively. A total of 1,394 molt-related differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analysis identified some important processes and pathways with key roles in molting regulation, such as chitin metabolism, peptidase inhibitor activity, and the ribosome. We first observed a pattern associated with the neuromodulator-related pathways during the molting cycle, which were up-regulated in PrM and down-regulated in PoM. Four categories of important molting-related transcripts were clustered and most of them had similar expression patterns, which suggests that there is a connection between these genes throughout the molt cycle. Conclusion Our work is the first molt-related investigation of P. trituberculatus focusing on the eyestalk at the whole transcriptome level. Together, our results, including DEGs, identification of molting-related biological processes and pathways, and observed expression patterns of important genes, provide a novel insight into the function of the eyestalk in molting regulation. PMID:28394948

[Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides].

PubMed

Sun, Xudong; Zhang, Lingyi; Zhang, Weibing

2017-07-08

Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO 2 ). The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N -linked glycopeptides. The Cys-Mal@SiO 2 demonstrated better identification capability over Cys@SiO 2 , Mal@SiO 2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO 2 . In addition, 1551 unique glycopeptides with 906 N -glycosylation sites from 466 different N -linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO 2 . In contrast, the numbers of identified glycopeptides, glycoproteins and N -glycosylation sites identified by Cys@SiO 2 were 211, 67, 127 respectively less than by Cys-Mal@SiO 2 , and the corresponding numbers were 289, 76, 193 by Mal@SiO 2 . These results showed that the developed Cys-Mal@SiO 2 is a promising affinity material for N -glycoproteomics research of real complex biological samples.

Indices, multispecies and synthesis descriptors in benthic assessments: Intertidal organic enrichment from oyster farming

NASA Astrophysics Data System (ADS)

Quintino, Victor; Azevedo, Ana; Magalhães, Luísa; Sampaio, Leandro; Freitas, Rosa; Rodrigues, Ana Maria; Elliott, Michael

2012-09-01

Intertidal off-bottom oyster culture is shown to cause organic enrichment of the shore and although there are two stressors of interest (the presence of a structure, the trestles, and also the sediment and organic waste from the oysters), these can be separated and their relative impacts determined using an appropriate nested experimental design and data treatments. Although no artificial food sources are involved, the oysters feeding activity and intensity of culture enhances biodeposition and significantly increases the sediment fines content and total organic matter. This in general impoverished the benthic community in culture areas rather than a species succession with the installation of opportunists or a resulting increase in the abundance and biomass of benthic species; the findings can be a direct consequence of the intertidal situation which is less-amenable recruitment of species more common to the subtidal environment. Thus the most appropriate biological descriptors to diagnose the effects associated with the organic enrichment were the multispecies abundance data as well as the primary biological variables species richness and abundance. The effects were however spatially and statistically significantly confined to the area located directly underneath the culture bags compared to the corridors located between the trestles, which do not show such enrichment effects. Synthesis biotic indices were much less effective to diagnose the benthic alterations associated with this organic enrichment. These results show that special attention must be paid when using indices in areas where the organic enrichment induces an impoverishment of the benthic community but not necessarily a species replacement with the installation of opportunists.

Defining the gene expression signature of rhabdomyosarcoma by meta-analysis

PubMed Central

Romualdi, Chiara; De Pittà, Cristiano; Tombolan, Lucia; Bortoluzzi, Stefania; Sartori, Francesca; Rosolen, Angelo; Lanfranchi, Gerolamo

2006-01-01

Background Rhabdomyosarcoma is a highly malignant soft tissue sarcoma in childhood and arises as a consequence of regulatory disruption of the growth and differentiation pathways of myogenic precursor cells. The pathogenic pathways involved in this tumor are mostly unknown and therefore a better characterization of RMS gene expression profile would represent a considerable advance. The availability of publicly available gene expression datasets have opened up new challenges especially for the integration of data generated by different research groups and different array platforms with the purpose of obtaining new insights on the biological process investigated. Results In this work we performed a meta-analysis on four microarray and two SAGE datasets of gene expression data on RMS in order to evaluate the degree of agreement of the biological results obtained by these different studies and to identify common regulatory pathways that could be responsible of tumor growth. Regulatory pathways and biological processes significantly enriched has been investigated and a list of differentially meta-profiles have been identified as possible candidate of aggressiveness of RMS. Conclusion Our results point to a general down regulation of the energy production pathways, suggesting a hypoxic physiology for RMS cells. This result agrees with the high malignancy of RMS and with its resistance to most of the therapeutic treatments. In this context, different isoforms of the ANT gene have been consistently identified for the first time as differentially expressed in RMS. This gene is involved in anti-apoptotic processes when cells grow in low oxygen conditions. These new insights in the biological processes responsible of RMS growth and development demonstrate the effective advantage of the use of integrated analysis of gene expression studies. PMID:17090319

Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation.

PubMed

Amato, Roberto; Pinelli, Michele; Monticelli, Antonella; Miele, Gennaro; Cocozza, Sergio

2010-11-11

Many natural phenomena are directly or indirectly related to latitude. Living at different latitudes, indeed, has its consequences with being exposed to different climates, diets, light/dark cycles, etc. In humans, one of the best known examples of genetic traits following a latitudinal gradient is skin pigmentation. Nevertheless, also several diseases show latitudinal clinals such as hypertension, cancer, dismetabolic conditions, schizophrenia, Parkinson's disease and many more. We investigated, for the first time on a wide genomic scale, the latitude-driven adaptation phenomena. In particular, we selected a set of genes showing signs of latitude-dependent population differentiation. The biological characterization of these genes showed enrichment for neural-related processes. In light of this, we investigated whether genes associated to neuropsychiatric diseases were enriched by Latitude-Related Genes (LRGs). We found a strong enrichment of LRGs in the set of genes associated to schizophrenia. In an attempt to try to explain this possible link between latitude and schizophrenia, we investigated their associations with vitamin D. We found in a set of vitamin D related genes a significant enrichment of both LRGs and of genes involved in schizophrenia. Our results suggest a latitude-driven adaptation for both schizophrenia and vitamin D related genes. In addition we confirm, at a molecular level, the link between schizophrenia and vitamin D. Finally, we discuss a model in which schizophrenia is, at least partly, a maladaptive by-product of latitude dependent adaptive changes in vitamin D metabolism.

Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology

PubMed Central

Moreno, Marta; Fernández, Virginia; Monllau, Josep M.; Borrell, Víctor; Lerin, Carles; de la Iglesia, Núria

2015-01-01

Summary Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state. PMID:26235896

DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis.

PubMed

Yu, Guangchuang; Wang, Li-Gen; Yan, Guang-Rong; He, Qing-Yu

2015-02-15

Disease ontology (DO) annotates human genes in the context of disease. DO is important annotation in translating molecular findings from high-throughput data to clinical relevance. DOSE is an R package providing semantic similarity computations among DO terms and genes which allows biologists to explore the similarities of diseases and of gene functions in disease perspective. Enrichment analyses including hypergeometric model and gene set enrichment analysis are also implemented to support discovering disease associations of high-throughput biological data. This allows biologists to verify disease relevance in a biological experiment and identify unexpected disease associations. Comparison among gene clusters is also supported. DOSE is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (http://www.bioconductor.org/packages/release/bioc/html/DOSE.html). Supplementary data are available at Bioinformatics online. gcyu@connect.hku.hk or tqyhe@jnu.edu.cn. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Enhancement of anaerobic methanogenesis at a short hydraulic retention time via bioelectrochemical enrichment of hydrogenotrophic methanogens.

PubMed

Li, Yang; Zhang, Yaobin; Liu, Yiwen; Zhao, Zhiqiang; Zhao, Zisheng; Liu, Sitong; Zhao, Huimin; Quan, Xie

2016-10-01

Anaerobic digestion (AD) is an important energy strategy for converting organic waste to CH4. A major factor limiting the practical applicability of AD is the relatively long hydraulic retention time (HRT) which declines the treatment efficiency of digesters. A coupling process of anaerobic digestion and 'electromethanogenesis' was proposed to enhance anaerobic digestion at a short HRT in this study. Microorganisms analysis indicated that the electric-biological reactor enriched hydrogenotrophic methanogens in both cathodic biofilm and suspended sludge, helping achieve the high organic removal (71.0% vs 42.3% [control reactor]) and CH4 production (248.5mL/h vs 51.3mL/h), while the additional electric input was only accounted for 25.6% of the energy income from the increased CH4 production. This study demonstrated that a bioelectrochemical enhanced anaerobic reactor could improve the CH4 production and organic removal at a short HRT, providing an economically feasible scheme to treat wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electroactive Biofilms: Current Status and Future Research Needs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borole, Abhijeet P; Reguera, Gemma; Ringeisen, Bradley

2011-01-01

Electroactive biofilms generated by electrochemically active microorganisms have many potential applications in bioenergy and chemicals production. This review assesses the effects of microbiological and process parameters on enrichment of such biofilms as well as critically evaluates the current knowledge of the mechanisms of extracellular electron transfer in BES systems. First we discuss the role of biofilm forming microorganisms vs. planktonic microorganisms. Physical, chemical and electrochemical parameters which dictate the enrichment and subsequent performance of the biofilms are discussed. Potential dependent biological parameters including biofilm growth rate, specific electron transfer rate and others and their relationship to BES system performance ismore » assessed. A review of the mechanisms of electron transfer in BES systems is included followed by a discussion of biofilm and its exopolymeric components and their electrical conductivity. A discussion of the electroactive biofilms in biocathodes is also included. Finally, we identify the research needs for further development of the electroactive biofilms to enable commercial applications.« less

Bioavailable metals in tourist beaches of Richards Bay, Kwazulu-Natal, South Africa.

PubMed

Vetrimurugan, E; Jonathan, M P; Roy, Priyadarsi D; Shruti, V C; Ndwandwe, O M

2016-04-15

Acid Leachable Trace Metal (ALTMs) concentrations in tourist beaches of Richards Bay, Kwazulu-Natal, South Africa were assessed. 53 surface sediment samples were collected from five different beaches (Kwambonambi Long Beach; Nhlabane Beach; Five Mile Beach; Alkanstrand Beach and Port Durnford Beach). The results of ALTMs (Fe, Mn, Cr, Cu, Ni, Co, Pb, Cd, Zn, As, Hg) suggest that they are enriched naturally and with some local industrial sources for (avg. in μgg(-1)) Fe (3530-7219), Mn (46-107.11), Cd (0.43-1.00) and Zn (48-103.98). Statistical results indicate that metal concentrations were from natural origin attributed to leaching, weathering process and industrial sources. Comparative studies of metal concentrations with sediment quality guidelines and ecotoxicological values indicate that there is no adverse biological effect. Enrichment factor and geoaccumulation indices results indicate moderate enhancement of Fe (Igeo class 1 in FMB), Cd (EF>50; Igeo classes 2-4) and Zn (Igeo classes 1 & 2). Copyright © 2016 Elsevier Ltd. All rights reserved.

Detecting cooperative sequences in the binding of RNA Polymerase-II

NASA Astrophysics Data System (ADS)

Glass, Kimberly; Rozenberg, Julian; Girvan, Michelle; Losert, Wolfgang; Ott, Ed; Vinson, Charles

2008-03-01

Regulation of the expression level of genes is a key biological process controlled largely by the 1000 base pair (bp) sequence preceding each gene (the promoter region). Within that region transcription factor binding sites (TFBS), 5-10 bp long sequences, act individually or cooperate together in the recruitment of, and therefore subsequent gene transcription by, RNA Polymerase-II (RNAP). We have measured the binding of RNAP to promoters on a genome-wide basis using Chromatin Immunoprecipitation (ChIP-on-Chip) microarray assays. Using all 8-base pair long sequences as a test set, we have identified the DNA sequences that are enriched in promoters with high RNAP binding values. We are able to demonstrate that virtually all sequences enriched in such promoters contain a CpG dinucleotide, indicating that TFBS that contain the CpG dinucleotide are involved in RNAP binding to promoters. Further analysis shows that the presence of pairs of CpG containing sequences cooperate to enhance the binding of RNAP to the promoter.

Enriching a Collaborative Teacher Inquiry Discourse: Exploring Teachers' Experiences of a Theory-Framed Discourse in a Singapore Case of Lesson Study

ERIC Educational Resources Information Center

Tan, Yuen Sze Michelle

2014-01-01

This paper explores how a learning theory enriched a collaborative teacher inquiry discourse where lesson study was adopted as the educational action research model to promote teacher professional development. Four Grade 9-10 biology teachers in Singapore drew from variation theory to collaboratively plan and teach new genetics content as part of…

Process for producing enriched uranium having a .sup.235 U content of at least 4 wt. % via combination of a gaseous diffusion process and an atomic vapor laser isotope separation process to eliminate uranium hexafluoride tails storage

DOEpatents

Horton, James A.; Hayden, Jr., Howard W.

1995-01-01

An uranium enrichment process capable of producing an enriched uranium, having a .sup.235 U content greater than about 4 wt. %, is disclosed which will consume less energy and produce metallic uranium tails having a lower .sup.235 U content than the tails normally produced in a gaseous diffusion separation process and, therefore, eliminate UF.sub.6 tails storage and sharply reduce fluorine use. The uranium enrichment process comprises feeding metallic uranium into an atomic vapor laser isotope separation process to produce an enriched metallic uranium isotopic mixture having a .sup.235 U content of at least about 2 wt. % and a metallic uranium residue containing from about 0.1 wt. % to about 0.2 wt. % .sup.235 U; fluorinating this enriched metallic uranium isotopic mixture to form UF.sub.6 ; processing the resultant isotopic mixture of UF.sub.6 in a gaseous diffusion process to produce a final enriched uranium product having a .sup.235 U content of at least 4 wt. %, and up to 93.5 wt. % or higher, of the total uranium content of the product, and a low .sup.235 U content UF.sub.6 having a .sup.235 U content of about 0.71 wt. % of the total uranium content of the low .sup.235 U content UF.sub.6 ; and converting this low .sup.235 U content UF.sub.6 to metallic uranium for recycle to the atomic vapor laser isotope separation process.

Process for producing enriched uranium having a {sup 235}U content of at least 4 wt. % via combination of a gaseous diffusion process and an atomic vapor laser isotope separation process to eliminate uranium hexafluoride tails storage

DOEpatents

Horton, J.A.; Hayden, H.W. Jr.

1995-05-30

An uranium enrichment process capable of producing an enriched uranium, having a {sup 235}U content greater than about 4 wt. %, is disclosed which will consume less energy and produce metallic uranium tails having a lower {sup 235}U content than the tails normally produced in a gaseous diffusion separation process and, therefore, eliminate UF{sub 6} tails storage and sharply reduce fluorine use. The uranium enrichment process comprises feeding metallic uranium into an atomic vapor laser isotope separation process to produce an enriched metallic uranium isotopic mixture having a {sup 235} U content of at least about 2 wt. % and a metallic uranium residue containing from about 0.1 wt. % to about 0.2 wt. % {sup 235} U; fluorinating this enriched metallic uranium isotopic mixture to form UF{sub 6}; processing the resultant isotopic mixture of UF{sub 6} in a gaseous diffusion process to produce a final enriched uranium product having a {sup 235}U content of at least 4 wt. %, and up to 93.5 wt. % or higher, of the total uranium content of the product, and a low {sup 235}U content UF{sub 6} having a {sup 235}U content of about 0.71 wt. % of the total uranium content of the low {sup 235}U content UF{sub 6}; and converting this low {sup 235}U content UF{sub 6} to metallic uranium for recycle to the atomic vapor laser isotope separation process. 4 figs.

Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

PubMed Central

Ye, Hao; Ng, Hui Wen; Sakkiah, Sugunadevi; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

2016-01-01

Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD) and the Herbal Ingredients’ Targets (HIT) database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process. PMID:27023590

Apoptotic Cell Clearance in Development.

PubMed

Shklover, Jeny; Levy-Adam, Flonia; Kurant, Estee

2015-01-01

Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology. © 2015 Elsevier Inc. All rights reserved.

Amine-functionalized TiO₂ nanoparticles for highly selective enrichment of phosphopeptides.

PubMed

Liu, Hailong; Zhou, Jiahong; Huang, Heyong

2015-10-01

Specific enrichment of trace phosphoproteins or phosphopeptides from complex biological samples prior to mass spectrometry analysis is of profound significance for in-depth phosphoproteomics. In this work, an amine-functionalized TiO2 nano-material with N'[3-(trimethoxysilyl)-propyl] diethylenetriamine (TPDA) modified on the surface of nanoparticle TiO2 (TiO2@TPDA) was successfully designed and applied for the enrichment of phosphopeptides. Compared with pure TiO2, the novel prepared TiO2@TPDA possessed lower Lewis acidity, enhanced hydrophilicity and stronger affinity to phosphopeptides, and its performance for selective and effective enrichment of phosphopeptide was investigated by the standard protein digests and human serum. Copyright © 2015 Elsevier B.V. All rights reserved.

Coupling Flash LC with MS for enrichment and isolation of milk oligosaccharides for functional studies

PubMed Central

Strum, John S.; Aldredge, Danielle; Barile, Daniela; Lebrilla, Carlito B.

2013-01-01

Mass spectrometry has been coupled with flash liquid chromatography to yield new capabilities for isolating non-chromophoric material from complicated biological mixtures. A flash LC/MS/MS method enabled fraction collection of milk oligosaccharides from biological mixtures based on composition and structure. The method is compatible with traditional gas-pressure driven flow flash chromatography, widely employed in organic chemistry laboratories. The on-line mass detector enabled real-time optimization of chromatographic parameters to favor separation of oligosaccharides that would otherwise be indistinguishable from co-eluting components with a non-specific detector. Unlike previously described preparative LC/MS techniques, we have employed a dynamic flow connection that permits any flow rate from the flash system to be delivered from 1–200 mL/min without affecting the ionization conditions of the mass spectrometer. A new way of packing large amounts of graphitized carbon allowed the enrichment and separation of milligram quantities of structurally heterogeneous mixtures of human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). Abundant saccharide components in milk, such as lactose and lacto-N-tetraose, were separated from the rarer and less abundant oligosaccharides that have greater structural diversity and biological functionality. Neutral and acidic HMOs and BMOs were largely separated and enriched with a dual binary solvent system. PMID:22370281

Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

PubMed

Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

2017-07-01

Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks.

PubMed

Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E

2017-04-12

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

Interstellar Processes Leading to Molecular Deuterium Enrichment and Their Detection

NASA Technical Reports Server (NTRS)

Sandford, Scott A.; Kliss, Mark (Technical Monitor)

2001-01-01

Large deuterium (D) enrichments in meteoritic materials indicate that interstellar organic materials survived incorporation into parent bodies within the forming Solar System. These enrichments are likelier due to one or more of four distinct astrochemical processes. These are (1) low temperature gas phase ion-molecule reactions; (2) low temperature gas-grain reactions; (3) gas phase unimolecular photodissociation, and (4) ultraviolet photolysis in D-enriched ice mantles. Each of these processes should be associated with molecular carriers having, distinct regiochemical signatures (D placement on the product molecules, correlation with specific chemical functionalities, etc.). These processes are reviewed and specific spectroscopic signatures for the detection of these processes in space are identified and described.

A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration.

PubMed

Huang, Lin; Lv, Qi; Liu, Fenfen; Shi, Tieliu; Wen, Chengping

2015-11-12

Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.

Stable Carbon Isotope Fractionation during Bacterial Acetylene Fermentation: Potential for Life Detection in Hydrocarbon-Rich Volatiles of Icy Planet(oid)s.

PubMed

Miller, Laurence G; Baesman, Shaun M; Oremland, Ronald S

2015-11-01

We report the first study of stable carbon isotope fractionation during microbial fermentation of acetylene (C2H2) in sediments, sediment enrichments, and bacterial cultures. Kinetic isotope effects (KIEs) averaged 3.7 ± 0.5‰ for slurries prepared with sediment collected at an intertidal mudflat in San Francisco Bay and 2.7 ± 0.2‰ for a pure culture of Pelobacter sp. isolated from these sediments. A similar KIE of 1.8 ± 0.7‰ was obtained for methanogenic enrichments derived from sediment collected at freshwater Searsville Lake, California. However, C2H2 uptake by a highly enriched mixed culture (strain SV7) obtained from Searsville Lake sediments resulted in a larger KIE of 9.0 ± 0.7‰. These are modest KIEs when compared with fractionation observed during oxidation of C1 compounds such as methane and methyl halides but are comparable to results obtained with other C2 compounds. These observations may be useful in distinguishing biologically active processes operating at distant locales in the Solar System where C2H2 is present. These locales include the surface of Saturn's largest moon Titan and the vaporous water- and hydrocarbon-rich jets emanating from Enceladus. Acetylene-Fermentation-Isotope fractionation-Enceladus-Life detection.

Dimethylated H3K27 Is a Repressive Epigenetic Histone Mark in the Protist Entamoeba histolytica and Is Significantly Enriched in Genes Silenced via the RNAi Pathway*

PubMed Central

Foda, Bardees M.; Singh, Upinder

2015-01-01

RNA interference (RNAi) is a fundamental biological process that plays a crucial role in regulation of gene expression in many organisms. Transcriptional gene silencing (TGS) is one of the important nuclear roles of RNAi. Our previous data show that Entamoeba histolytica has a robust RNAi pathway that links to TGS via Argonaute 2-2 (Ago2-2) associated 27-nucleotide small RNAs with 5′-polyphosphate termini. Here, we report the first repressive histone mark to be identified in E. histolytica, dimethylation of H3K27 (H3K27Me2), and demonstrate that it is enriched at genes that are silenced by RNAi-mediated TGS. An RNAi-silencing trigger can induce H3K27Me2 deposits at both episomal and chromosomal loci, mediating gene silencing. Our data support two phases of RNAi-mediated TGS: an active silencing phase where the RNAi trigger is present and both H3K27Me2 and Ago2-2 concurrently enrich at chromosomal loci; and an established silencing phase in which the RNAi trigger is removed, but gene silencing with H3K27Me2 enrichment persist independently of Ago2-2 deposition. Importantly, some genes display resistance to chromosomal silencing despite induction of functional small RNAs. In those situations, the RNAi-triggering plasmid that is maintained episomally gets partially silenced and has H3K27Me2 enrichment, but the chromosomal copy displays no repressive histone enrichment. Our data are consistent with a model in which H3K27Me2 is a repressive histone modification, which is strongly associated with transcriptional repression. This is the first example of an epigenetic histone modification that functions to mediate RNAi-mediated TGS in the deep-branching eukaryote E. histolytica. PMID:26149683

Chiral Polychlorinated Biphenyl Transport, Metabolism and Distribution - A Review

PubMed Central

Lehmler, Hans-Joachim; Harrad, Stuart J.; Hühnerfuss, Heinrich; Kania-Korwel, Izabela; Lee, Cindy M.; Lu, Zhe; Wong, Charles S.

2009-01-01

Chirality can be exploited to gain insight into enantioselective fate processes that may otherwise remain undetected because only biological, but not physical and chemical transport and transformation processes in an achiral environment will change enantiomer compositions. This review provides an in-depth overview of the application of chirality to the study of chiral polychlorinated biphenyls (PCBs), an important group of legacy pollutants. Like other chiral compounds, individual PCB enantiomers may interact enantioselectively (or enantiospecifically) with chiral macromolecules, such as cytochrome P-450 enzymes or ryanodine receptors, leading to differences in their toxicological effects and the enantioselective formation of chiral biotransformation products. Species and congener-specific enantiomer enrichment has been demonstrated in environmental compartments, wildlife and mammals, including humans, typically due to a complex combination of biotransformation processes and uptake via the diet by passive diffusion. Changes in the enantiomer composition of chiral PCBs in the environment have been used to understand complex aerobic and anaerobic microbial transformation pathways, to delineate and quantify PCB sources and transport in the environment, to gain insight into the biotransformation of PCBs in aquatic food webs, and to investigate the enantioselective disposition of PCBs and their methylsulfonyl PCBs metabolites in rodents. Overall, changes in chiral signatures are powerful, but currently underutilized tools for studies of environmental and biological processes of PCBs. PMID:20384371

Long-term expression of glomerular genes in diabetic nephropathy.

PubMed

Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

2018-01-11

Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney injury. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A cost-effective method to get insight into the peritoneal dialysate effluent proteome.

PubMed

Araújo, J E; Jorge, S; Teixeira E Costa, F; Ramos, A; Lodeiro, C; Santos, H M; Capelo, J L

2016-08-11

Protein depletion with acetonitrile and protein equalization with dithiothreitol have been assessed with success as proteomics tools for getting insight into the peritoneal dialysate effluent proteome. The methods proposed are cost-effective, fast and easy of handling, and they match the criteria of analytical minimalism: low sample volume and low reagent consumption. Using two-dimensional gel electrophoresis and peptide mass fingerprinting, a total of 72 unique proteins were identified. Acetonitrile depletes de PDE proteome from high-abundance proteins, such as albumin, and enriches the sample in apolipo-like proteins. Dithiothreitol equalizes the PDE proteome by diminishing the levels of albumin and enriching the extract in immunoglobulin-like proteins. The annotation per gene ontology term reveals the same biological paths being affected for patients undergoing peritoneal dialysis, namely that the largest number of proteins lost through peritoneal dialysate are extracellular proteins involved in regulation processes through binding. Renal failure is a growing problem worldwide, and particularly in Europe where the population is getting older. Up-to-date there is a focus of interest in peritoneal dialysis (PD), as it provides a better quality of life and autonomy of the patients than other renal replacement therapies such as haemodialysis. However, PD can only be used during a short period of years, as the peritoneum lost its permeability through time. Therefore to make a breakthrough in PD and consequently contribute to better healthcare system it is urgent to find a group of biomarkers of peritoneum degradation. Here we report on two cost-effective methods for protein depletion in peritoneal dialysate effluent (PDE). The use of ACN and DTT over PDE to deplete high abundant proteins or to equalize the concentration of proteins, respectively, performs well and with similar protein profiles than when the same chemicals are used in human plasma samples. ACN depletes de PDE proteome from large proteins, such as albumin, and enriches the sample in apolipoproteins. DTT equalizes the PDE proteome by diminishing the levels of large proteins such as albumin and enriching the extract in immunoglobulins. Although the number and type of proteins identified are different, the annotation per gene ontology term reveals the same biological paths being affected for patients undergoing peritoneal dialysate. Thus, the largest number of proteins lost through peritoneal dialysate belongs to the group of extracellular proteins involved in regulation processes through binding. As for the searching of biomarkers, DTT seems to be the most promising of the two methods because acts as an equalizer and it allows interrogating more proteins in the same sample.

Changes in optical characteristics of surface microlayers hint to photochemically and microbially-mediated DOM turnover in the upwelling region off Peru

NASA Astrophysics Data System (ADS)

Galgani, L.; Engel, A.

2015-12-01

The coastal upwelling system off Peru is characterized by high biological activity and a pronounced subsurface oxygen minimum zone, as well as associated emissions of atmospheric trace gases such as N2O, CH4 and CO2. During the Meteor (M91) cruise to the Peruvian upwelling system in 2012, we investigated the composition of the sea-surface microlayer (SML), the oceanic uppermost boundary directly subject to high solar radiation, often enriched in specific organic compounds of biological origin like Chromophoric Dissolved Organic Matter (CDOM) and marine gels. In the SML, the continuous photochemical and microbial recycling of organic matter may strongly influence gas exchange between marine systems and the atmosphere. In order to understand organic matter cycling in surface films, we analyzed SML and underlying water samples at 38 stations determining DOC concentration, amino acid composition, marine gels, CDOM and bacterial and phytoplankton abundance as indicators of photochemical and microbial alteration processes. CDOM composition was characterized by spectral slope (S) values and Excitation-Emission Matrix fluorescence (EEMs), which allow to track changes in molecular weight (MW) of DOM, and to determine potential DOM sources and sinks. We identified five fluorescent components of the CDOM pool, of which two had excitation/emission characteristics of protein-like fluorophores and were highly enriched in the SML. CDOM composition and changes in spectral slope properties suggested a local microbial release of HMW DOM directly in the SML as a response to light exposure in this extreme environment. Our results suggest that microbial and photochemical processes play an important role for the production, alteration and loss of optically active substances in the SML.

Metagenomics-Enabled Understanding of Soil Microbial Feedbacks to Climate Warming

NASA Astrophysics Data System (ADS)

Zhou, J.; Wu, L.; Zhili, H.; Kostas, K.; Luo, Y.; Schuur, E. A. G.; Cole, J. R.; Tiedje, J. M.

2014-12-01

Understanding the response of biological communities to climate warming is a central issue in ecology and global change biology, but it is poorly understood microbial communities. To advance system-level predictive understanding of the feedbacks of belowground microbial communities to multiple climate change factors and their impacts on soil carbon (C) and nitrogen (N) cycling processes, we have used integrated metagenomic technologies (e.g., target gene and shotgun metagenome sequencing, GeoChip, and isotope) to analyze soil microbial communities from experimental warming sites in Alaska (AK) and Oklahoma (OK), and long-term laboratory incubation. Rapid feedbacks of microbial communities to warming were observed in the AK site. Consistent with the changes in soil temperature, moisture and ecosystem respiration, microbial functional community structure was shifted after only 1.5-year warming, indicating rapid responses and high sensitivity of this permafrost ecosystem to climate warming. Also, warming stimulated not only functional genes involved in aerobic respiration of both labile and recalcitrant C, contributing to an observed 24% increase in 2010 growing season and 56% increase of decomposition of a standard substrate, but also functional genes for anaerobic processes (e.g., denitrification, sulfate reduction, methanogenesis). Further comparisons by shotgun sequencing showed significant differences of microbial community structure between AK and OK sites. The OK site was enriched in genes annotated for cellulose degradation, CO2 production, denitrification, sporulation, heat shock response, and cellular surface structures (e.g., trans-membrane transporters for glucosides), while the AK warmed plots were enriched in metabolic pathways related to labile C decomposition. Together, our results demonstrate the vulnerability of permafrost ecosystem C to climate warming and the importance of microbial feedbacks in mediating such vulnerability.

Performance impact of dynamic surface coatings on polymeric insulator-based dielectrophoretic particle separators.

PubMed

Davalos, Rafael V; McGraw, Gregory J; Wallow, Thomas I; Morales, Alfredo M; Krafcik, Karen L; Fintschenko, Yolanda; Cummings, Eric B; Simmons, Blake A

2008-02-01

Efficient and robust particle separation and enrichment techniques are critical for a diverse range of lab-on-a-chip analytical devices including pathogen detection, sample preparation, high-throughput particle sorting, and biomedical diagnostics. Previously, using insulator-based dielectrophoresis (iDEP) in microfluidic glass devices, we demonstrated simultaneous particle separation and concentration of various biological organisms, polymer microbeads, and viruses. As an alternative to glass, we evaluate the performance of similar iDEP structures produced in polymer-based microfluidic devices. There are numerous processing and operational advantages that motivate our transition to polymers such as the availability of numerous innate chemical compositions for tailoring performance, mechanical robustness, economy of scale, and ease of thermoforming and mass manufacturing. The polymer chips we have evaluated are fabricated through an injection molding process of the commercially available cyclic olefin copolymer Zeonor 1060R. This publication is the first to demonstrate insulator-based dielectrophoretic biological particle differentiation in a polymeric device injection molded from a silicon master. The results demonstrate that the polymer devices achieve the same performance metrics as glass devices. We also demonstrate an effective means of enhancing performance of these microsystems in terms of system power demand through the use of a dynamic surface coating. We demonstrate that the commercially available nonionic block copolymer surfactant, Pluronic F127, has a strong interaction with the cyclic olefin copolymer at very low concentrations, positively impacting performance by decreasing the electric field necessary to achieve particle trapping by an order of magnitude. The presence of this dynamic surface coating, therefore, lowers the power required to operate such devices and minimizes Joule heating. The results of this study demonstrate that iDEP polymeric microfluidic devices with surfactant coatings provide an affordable engineering strategy for selective particle enrichment and sorting.

The nuclear proteome of Trypanosoma brucei

PubMed Central

Goos, Carina; Dejung, Mario; Janzen, Christian J.; Butter, Falk

2017-01-01

Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host. Here, we provide the nuclear proteome of procyclic Trypanosoma brucei, the stage that resides within the tsetse fly midgut. We have performed quantitative label-free mass spectrometry to score 764 significantly nuclear enriched proteins in comparison to whole cell lysates. A comparison with proteomes of several experimentally characterised nuclear and non-nuclear structures and pathways confirmed the high quality of the dataset: the proteome contains about 80% of all nuclear proteins and less than 2% false positives. Using motif enrichment, we found the amino acid sequence KRxR present in a large number of nuclear proteins. KRxR is a sub-motif of a classical eukaryotic monopartite nuclear localisation signal and could be responsible for nuclear localization of proteins in Kinetoplastida species. As a proof of principle, we have confirmed the nuclear localisation of six proteins with previously unknown localisation by expressing eYFP fusion proteins. While proteome data of several T. brucei organelles have been published, our nuclear proteome closes an important gap in knowledge to study trypanosome biology, in particular nuclear-related processes. PMID:28727848

Analysis of Gene Expression Changes in PHA-M Stimulated Lymphocytes - Unraveling PHA Activity as Prerequisite for Dicentric Chromosome Analysis.

PubMed

Beinke, C; Port, M; Ullmann, R; Gilbertz, K; Majewski, M; Abend, M

2018-06-01

Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose assessment. However, DCA is limited by the time-consuming phytohemagglutinin (PHA)-mediated lymphocyte activation. In this study using human peripheral blood lymphocytes, we investigated PHA-associated whole genome gene expression changes to elucidate this process and sought to identify suitable gene targets as a means of meeting our long-term objective of accelerating cell cycle kinetics to reduce DCA culture time. Human peripheral whole blood from three healthy donors was separately cultured in RPMI/FCS/antibiotics with BrdU and PHA-M. Diluted whole blood samples were transferred into PAXgene tubes at 0, 12, 24 and 36 h culture time. RNA was isolated and aliquots were used for whole genome gene expression screening. Microarray results were validated using qRT-PCR and differentially expressed genes [significantly (FDR corrected) twofold different from the 0 h value reference] were analyzed using several bioinformatic tools. The cell cycle positions and DNA-synthetic activities of lymphocytes were determined by analyzing the correlated total DNA content and incorporated BrdU level with flow cytometry after continued BrdU incubation. From 42,545 transcripts of the whole genome microarray 47.6%, on average, appeared expressed. The number of differentially expressed genes increased linearly from 855 to 2,858 and 4,607 at 12, 24 and 36 h after PHA addition, respectively. Approximately 2-3 times more up- than downregulated genes were observed with several hundred genes differentially expressed at each time point. Earliest enrichment was observed for gene sets related to the nucleus (12 h) followed by genes assigned to intracellular structures such as organelles (24 h) and finally genes related to the membrane and the extracellular matrix were enriched (36 h). Early gene expression changes at 12 h, in particular, were associated with protein classes such as chemokines/cytokines (e.g., CXCL1, CXCL2) and chaperones. Genes coding for biological processes involved in cell cycle control (e.g., MYBL2, RBL1, CCNA, CCNE) and DNA replication (e.g., POLA, POLE, MCM) appeared enriched at 24 h and later, but many more biological processes (42 altogether) showed enrichment as well. Flow cytometry data fit together with gene expression and bioinformatic analyses as cell cycle transition into S phase was observed with interindividual differences from 12 h onward, whereas progression into G 2 as well as into the second G 1 occurred from 36 h onward after activation. Gene set enrichment analysis over time identifies, in particular, two molecular categories of PHA-responsive gene targets (cytokine and cell cycle control genes). Based on that analysis target genes for cell cycle acceleration in lymphocytes have been identified ( CDKN1A/B/C, RBL-1/RBL-2, E2F2, Deaf-1), and it remains undetermined whether the time expenditure for DCA can be reduced by influencing gene expression involved in the regulatory circuits controlling PHA-associated cell cycle entry and/or progression at a specific early cell cycle phase.

An enrichment method based on synergistic and reversible covalent interactions for large-scale analysis of glycoproteins.

PubMed

Xiao, Haopeng; Chen, Weixuan; Smeekens, Johanna M; Wu, Ronghu

2018-04-27

Protein glycosylation is ubiquitous in biological systems and essential for cell survival. However, the heterogeneity of glycans and the low abundance of many glycoproteins complicate their global analysis. Chemical methods based on reversible covalent interactions between boronic acid and glycans have great potential to enrich glycopeptides, but the binding affinity is typically not strong enough to capture low-abundance species. Here, we develop a strategy using dendrimer-conjugated benzoboroxole to enhance the glycopeptide enrichment. We test the performance of several boronic acid derivatives, showing that benzoboroxole markedly increases glycopeptide coverage from human cell lysates. The enrichment is further improved by conjugating benzoboroxole to a dendrimer, which enables synergistic benzoboroxole-glycan interactions. This robust and simple method is highly effective for sensitive glycoproteomics analysis, especially capturing low-abundance glycopeptides. Importantly, the enriched glycopeptides remain intact, making the current method compatible with mass-spectrometry-based approaches to identify glycosylation sites and glycan structures.

Biotransformation of RDX and HMX by Anaerobic Granular Sludge with Enriched Sulfate and Nitrate.

PubMed

An, Chunjiang; Shi, Yarong; He, Yanling; Huang, Guohe; Liu, Yonghong; Yang, Shucheng

2017-05-01

  RDX and HMX are widely used energetic materials and they are recognized as environmental contaminants at numerous locations. The present study investigated the biotransformation of RDX and HMX by anaerobic granular sludge under sulfate- and nitrate-enriched conditions. The results showed that RDX and HMX could be transformed by anaerobic granular sludge when nitrate was present. However, the biotransformation of RDX and HMX was negatively influenced, especially with high nitrate concentrations. Sulfate-enriched conditions were more favorable for the removal of ammunition compounds by anaerobic granular sludge than nitrate-enriched conditions. The removal of RDX and HMX under both nitrate- and sulfate-enriched conditions was facilitated by the use of glucose as additional substrate. This knowledge may help identify factors required for rapid removal of RDX and HMX in high-rate bioreactors. These results can also be applied to devise an appropriate and practical biological treatment strategy for explosive contaminated wastewater.

The plasma separation process as a pre-cursor for large scale radioisotope production

NASA Astrophysics Data System (ADS)

Stevenson, Nigel R.

2001-07-01

Radioisotope production generally employs either accelerators or reactors to convert stable (usually enriched) isotopes into the desired product species. Radioisotopes have applications in industry, environmental sciences, and most significantly in medicine. The production of many potentially useful radioisotopes is significantly hindered by the lack of availability or by the high cost of key enriched stable isotopes. To try and meet this demand, certain niche enrichment processes have been developed and commercialized. Calutrons, centrifuges, and laser separation processes are some of the devices and techniques being employed to produce large quantities of selective enriched stable isotopes. Nevertheless, the list of enriched stable isotopes in sufficient quantities remains rather limited and this continues to restrict the availability of many radioisotopes that otherwise could have a significant impact on society. The Plasma Separation Process is a newly available commercial technique for producing large quantities of a wide range of enriched isotopes and thereby holds promise of being able to open the door to producing new and exciting applications of radioisotopes in the future.

Response and adaptation of photosynthesis, respiration, and antioxidant systems to elevated CO2 with environmental stress in plants

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Zhou, Guangsheng

2015-01-01

It is well known that plant photosynthesis and respiration are two fundamental and crucial physiological processes, while the critical role of the antioxidant system in response to abiotic factors is still a focus point for investigating physiological stress. Although one key metabolic process and its response to climatic change have already been reported and reviewed, an integrative review, including several biological processes at multiple scales, has not been well reported. The current review will present a synthesis focusing on the underlying mechanisms in the responses to elevated CO2 at multiple scales, including molecular, cellular, biochemical, physiological, and individual aspects, particularly, for these biological processes under elevated CO2 with other key abiotic stresses, such as heat, drought, and ozone pollution, as well as nitrogen limitation. The present comprehensive review may add timely and substantial information about the topic in recent studies, while it presents what has been well established in previous reviews. First, an outline of the critical biological processes, and an overview of their roles in environmental regulation, is presented. Second, the research advances with regard to the individual subtopics are reviewed, including the response and adaptation of the photosynthetic capacity, respiration, and antioxidant system to CO2 enrichment alone, and its combination with other climatic change factors. Finally, the potential applications for plant responses at various levels to climate change are discussed. The above issue is currently of crucial concern worldwide, and this review may help in a better understanding of how plants deal with elevated CO2 using other mainstream abiotic factors, including molecular, cellular, biochemical, physiological, and whole individual processes, and the better management of the ecological environment, climate change, and sustainable development. PMID:26442017

Digital gene expression profiling of flax (Linum usitatissimum L.) stem peel identifies genes enriched in fiber-bearing phloem tissue.

PubMed

Guo, Yuan; Qiu, Caisheng; Long, Songhua; Chen, Ping; Hao, Dongmei; Preisner, Marta; Wang, Hui; Wang, Yufu

2017-08-30

To better understand the molecular mechanisms and gene expression characteristics associated with development of bast fiber cell within flax stem phloem, the gene expression profiling of flax stem peels and leaves were screened, using Illumina's Digital Gene Expression (DGE) analysis. Four DGE libraries (2 for stem peel and 2 for leaf), ranging from 6.7 to 9.2 million clean reads were obtained, which produced 7.0 million and 6.8 million mapped reads for flax stem peel and leave, respectively. By differential gene expression analysis, a total of 975 genes, of which 708 (73%) genes have protein-coding annotation, were identified as phloem enriched genes putatively involved in the processes of polysaccharide and cell wall metabolism. Differential expression genes (DEGs) was validated using quantitative RT-PCR, the expression pattern of all nine genes determined by qRT-PCR fitted in well with that obtained by sequencing analysis. Cluster and Gene Ontology (GO) analysis revealed that a large number of genes related to metabolic process, catalytic activity and binding category were expressed predominantly in the stem peels. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the phloem enriched genes suggested approximately 111 biological pathways. The large number of genes and pathways produced from DGE sequencing will expand our understanding of the complex molecular and cellular events in flax bast fiber development and provide a foundation for future studies on fiber development in other bast fiber crops. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential gene expression in the intestine of sea cucumber (Apostichopus japonicus) under low and high salinity conditions.

PubMed

Zhang, Libin; Feng, Qiming; Sun, Lina; Ding, Kui; Huo, Da; Fang, Yan; Zhang, Tao; Yang, Hongsheng

2018-03-01

Sea cucumber, Apostichopus japonicus is an important species for aquaculture, and its behavior and physiology can change in response to changing salinity conditions. For this reason, it is important to understand the molecular responses of A. japonicus when exposed to ambient changes in salinity. In this study, RNA-Seq provided a general overview of the gene expression profiles in the intestine of A. japonicus exposed to high salinity (SD40), normal salinity (SD30) and low salinity (SD20) environments. Screening for differentially expressed genes (DEGs) using the NOISeq method identified 109, 100, and 89 DEGs based on a fold change of ≥2 and divergence probability ≥0.8 according to the comparisons of SD20 vs. SD30, SD20 vs.SD40, and SD30 vs. SD40, respectively. Gene ontology analysis showed that the terms "metabolic process" and "catalytic activity" comprised the most enriched DEGs. These fell into the categories of "biological process" and "molecular function". While "cell" and "cell part" had the most enriched DEGs in the category of "cellular component". With these DEGs mapping to 2119, 159, and 160 pathways in the Kyoto Encyclopedia of Genes and Genomes database. Of these 51, 2, and 57 pathways were significantly enriched, respectively. The osmosis-specific DEGs identified in this study of A. japonicus will be important targets for further studies to understand the biochemical mechanisms involved with the adaption of sea cucumbers to changes in salinity. Copyright © 2017. Published by Elsevier Inc.

Identification of karyopherins involved in the nuclear import of RNA exosome subunit Rrp6 in Saccharomyces cerevisiae.

PubMed

Gonzales-Zubiate, Fernando A; Okuda, Ellen K; Da Cunha, Julia P C; Oliveira, Carla Columbano

2017-07-21

The exosome is a conserved multiprotein complex essential for RNA processing and degradation. The nuclear exosome is a key factor for pre-rRNA processing through the activity of its catalytic subunits, Rrp6 and Rrp44. In Saccharomyces cerevisiae , Rrp6 is exclusively nuclear and has been shown to interact with exosome cofactors. With the aim of analyzing proteins associated with the nuclear exosome, in this work, we purified the complex with Rrp6-TAP, identified the co-purified proteins by mass spectrometry, and found karyopherins to be one of the major groups of proteins enriched in the samples. By investigating the biological importance of these protein interactions, we identified Srp1, Kap95, and Sxm1 as the most important karyopherins for Rrp6 nuclear import and the nuclear localization signals recognized by them. Based on the results shown here, we propose a model of multiple pathways for the transport of Rrp6 to the nucleus. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Targeted enrichment strategies for next-generation plant biology

Treesearch

Richard Cronn; Brian J. Knaus; Aaron Liston; Peter J. Maughan; Matthew Parks; John V. Syring; Joshua Udall

2012-01-01

The dramatic advances offered by modem DNA sequencers continue to redefine the limits of what can be accomplished in comparative plant biology. Even with recent achievements, however, plant genomes present obstacles that can make it difficult to execute large-scale population and phylogenetic studies on next-generation sequencing platforms. Factors like large genome...

Acoustic Enrichment of Extracellular Vesicles from Biological Fluids.

PubMed

Ku, Anson; Lim, Hooi Ching; Evander, Mikael; Lilja, Hans; Laurell, Thomas; Scheding, Stefan; Ceder, Yvonne

2018-06-11

Extracellular vesicles (EVs) have emerged as a rich source of biomarkers providing diagnostic and prognostic information in diseases such as cancer. Large-scale investigations into the contents of EVs in clinical cohorts are warranted, but a major obstacle is the lack of a rapid, reproducible, efficient, and low-cost methodology to enrich EVs. Here, we demonstrate the applicability of an automated acoustic-based technique to enrich EVs, termed acoustic trapping. Using this technology, we have successfully enriched EVs from cell culture conditioned media and urine and blood plasma from healthy volunteers. The acoustically trapped samples contained EVs ranging from exosomes to microvesicles in size and contained detectable levels of intravesicular microRNAs. Importantly, this method showed high reproducibility and yielded sufficient quantities of vesicles for downstream analysis. The enrichment could be obtained from a sample volume of 300 μL or less, an equivalent to 30 min of enrichment time, depending on the sensitivity of downstream analysis. Taken together, acoustic trapping provides a rapid, automated, low-volume compatible, and robust method to enrich EVs from biofluids. Thus, it may serve as a novel tool for EV enrichment from large number of samples in a clinical setting with minimum sample preparation.

Strawberry tannins inhibit IL-8 secretion in a cell model of gastric inflammation.

PubMed

Fumagalli, Marco; Sangiovanni, Enrico; Vrhovsek, Urska; Piazza, Stefano; Colombo, Elisa; Gasperotti, Mattia; Mattivi, Fulvio; De Fabiani, Emma; Dell'Agli, Mario

2016-09-01

In the present study we chemically profiled tannin-enriched extracts from strawberries and tested their biological properties in a cell model of gastric inflammation. The chemical and biological features of strawberry tannins after in vitro simulated gastric digestion were investigated as well. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human gastric epithelial cells by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affected the chemical composition and the biological properties of strawberry tannins. By using pure compounds, we found that casuarictin may act as a pure NF-κB inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. We conclude that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathway analysis of high-throughput biological data within a Bayesian network framework.

PubMed

Isci, Senol; Ozturk, Cengizhan; Jones, Jon; Otu, Hasan H

2011-06-15

Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC. Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa.

The multidimensional ionotropic receptors of Drosophila melanogaster.

PubMed

Rimal, S; Lee, Y

2018-02-01

Ionotropic receptors (IRs), which form ion channels, can be categorized into conserved 'antennal IRs', which define the first olfactory receptor family of insects, and species-specific 'divergent IRs', which are expressed in gustatory receptor neurones. These receptors are located primarily in cell bodies and dendrites, and are highly enriched in the tips of the dendritic terminals that convey sensory information to higher brain centres. Antennal IRs play important roles in odour and thermosensation, whereas divergent IRs are involved in other important biological processes such as taste sensation. Some IRs are known to play specific biological roles in the perception of various molecules; however, many of their functions have not yet been defined. Although progress has been made in this field, many functions and mechanisms of these receptors remain unknown. In this review, we provide a comprehensive summary of the current state of knowledge in this field. © 2017 The Royal Entomological Society.

Profiling the Serum Protein Corona of Fibrillar Human Islet Amyloid Polypeptide.

PubMed

Pilkington, Emily H; Gustafsson, Ove J R; Xing, Yanting; Hernandez-Fernaud, Juan; Zampronio, Cleidi; Kakinen, Aleksandr; Faridi, Ava; Ding, Feng; Wilson, Paul; Ke, Pu Chun; Davis, Thomas P

2018-05-16

Amyloids may be regarded as native nanomaterials that form in the presence of complex protein mixtures. By drawing an analogy with the physicochemical properties of nanoparticles in biological fluids, we hypothesized that amyloids should form a protein corona in vivo that would imbue the underlying amyloid with a modified biological identity. To explore this hypothesis, we characterized the protein corona of human islet amyloid polypeptide (IAPP) fibrils in fetal bovine serum using two complementary methodologies developed herein: quartz crystal microbalance and "centrifugal capture", coupled with nanoliquid chromatography tandem mass spectroscopy. Clear evidence for a significant protein corona was obtained. No trends were identified for amyloid corona proteins based on their physicochemical properties, whereas strong binding with IAPP fibrils occurred for linear proteins or multidomain proteins with structural plasticity. Proteomic analysis identified amyloid-enriched proteins that are known to play significant roles in mediating cellular machinery and processing, potentially leading to pathological outcomes and therapeutic targets.

CoPub: a literature-based keyword enrichment tool for microarray data analysis.

PubMed

Frijters, Raoul; Heupers, Bart; van Beek, Pieter; Bouwhuis, Maurice; van Schaik, René; de Vlieg, Jacob; Polman, Jan; Alkema, Wynand

2008-07-01

Medline is a rich information source, from which links between genes and keywords describing biological processes, pathways, drugs, pathologies and diseases can be extracted. We developed a publicly available tool called CoPub that uses the information in the Medline database for the biological interpretation of microarray data. CoPub allows batch input of multiple human, mouse or rat genes and produces lists of keywords from several biomedical thesauri that are significantly correlated with the set of input genes. These lists link to Medline abstracts in which the co-occurring input genes and correlated keywords are highlighted. Furthermore, CoPub can graphically visualize differentially expressed genes and over-represented keywords in a network, providing detailed insight in the relationships between genes and keywords, and revealing the most influential genes as highly connected hubs. CoPub is freely accessible at http://services.nbic.nl/cgi-bin/copub/CoPub.pl.

Insulin released from titanium discs with insulin coatings-Kinetics and biological activity.

PubMed

Malekzadeh, B Ö; Ransjo, M; Tengvall, P; Mladenovic, Z; Westerlund, A

2017-10-01

Local administration of insulin from a titanium surface has been demonstrated to increase bone formation in non-diabetic rats. The authors hypothesized that insulin was released from the titanium surface and with preserved biological activity after the release. Thus, in the present in vitro study, human recombinant insulin was immobilized onto titanium discs, and the insulin release kinetics was evaluated using Electro-chemiluminescence immunoassay. Neutral Red uptake assay and mineralization assay were used to evaluate the biological effects of the released insulin on human osteoblast-like MG-63 cells. The results confirmed that insulin was released from titanium surfaces during a six-week period. Etching the disc prior to insulin coating, thickening of the insulin coating and incubation of the discs in serum-enriched cell culture medium increased the release. However, longer storage time decreased the release of insulin. Furthermore, the released insulin had retained its biological activity, as demonstrated by the significant increase in cell number and a stimulated mineralization process, upon exposure to released insulin. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1847-1854, 2017. © 2016 Wiley Periodicals, Inc.

Population dynamics in controlled unsteady-state systems: An application to the degradation of glyphosate in a sequencing batch reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devarakonda, M.S.

1988-01-01

Control over population dynamics and organism selection in a biological waste treatment system provides an effective means of engineering process efficiency. Examples of applications of organism selection include control of filamentous organisms, biological nutrient removal, industrial waste treatment requiring the removal of specific substrates, and hazardous waste treatment. Inherently, full scale biological waste treatment systems are unsteady state systems due to the variations in the waste streams and mass flow rates of the substrates. Some systems, however, have the capacity to impose controlled selective pressures on the biological population by means of their operation. An example of such a systemmore » is the Sequencing Batch Reactor (SBR) which was the experimental system utilized in this research work. The concepts of organism selection were studied in detail for the biodegradation of a herbicide waste stream, with glyphosate as the target compound. The SBR provided a reactor configuration capable of exerting the necessary selective pressures to select and enrich for a glyphosate degrading population. Based on results for bench scale SBRs, a hypothesis was developed to explain population dynamics in glyphosate degrading systems.« less

Meta-analysis of pathway enrichment: combining independent and dependent omics data sets.

PubMed

Kaever, Alexander; Landesfeind, Manuel; Feussner, Kirstin; Morgenstern, Burkhard; Feussner, Ivo; Meinicke, Peter

2014-01-01

A major challenge in current systems biology is the combination and integrative analysis of large data sets obtained from different high-throughput omics platforms, such as mass spectrometry based Metabolomics and Proteomics or DNA microarray or RNA-seq-based Transcriptomics. Especially in the case of non-targeted Metabolomics experiments, where it is often impossible to unambiguously map ion features from mass spectrometry analysis to metabolites, the integration of more reliable omics technologies is highly desirable. A popular method for the knowledge-based interpretation of single data sets is the (Gene) Set Enrichment Analysis. In order to combine the results from different analyses, we introduce a methodical framework for the meta-analysis of p-values obtained from Pathway Enrichment Analysis (Set Enrichment Analysis based on pathways) of multiple dependent or independent data sets from different omics platforms. For dependent data sets, e.g. obtained from the same biological samples, the framework utilizes a covariance estimation procedure based on the nonsignificant pathways in single data set enrichment analysis. The framework is evaluated and applied in the joint analysis of Metabolomics mass spectrometry and Transcriptomics DNA microarray data in the context of plant wounding. In extensive studies of simulated data set dependence, the introduced correlation could be fully reconstructed by means of the covariance estimation based on pathway enrichment. By restricting the range of p-values of pathways considered in the estimation, the overestimation of correlation, which is introduced by the significant pathways, could be reduced. When applying the proposed methods to the real data sets, the meta-analysis was shown not only to be a powerful tool to investigate the correlation between different data sets and summarize the results of multiple analyses but also to distinguish experiment-specific key pathways.

Comparative Analysis of Transcriptomes of Macrophage Revealing the Mechanism of the Immunoregulatory Activities of a Novel Polysaccharide Isolated from Boletus speciosus Frost

PubMed Central

Ding, Xiang; Zhu, Hongqing; Hou, Yiling; Hou, Wanru; Zhang, Nan; Fu, Lei

2017-01-01

Background: The mechanism of the immunoregulatory activities of polysaccharide is still not clear. Materials and Methods: Here, we performed the B-cell, T-cell, and macrophage cell proliferation, the cell cycle analysis of macrophage cells, sequenced the transcriptomes of control group macrophages, and Boletus speciosus Frost polysaccharide (BSF-1) group macrophages using Illumina sequencing technology to identify differentially expressed genes (DEGs) to determine the molecular mechanisms of immunomodulatory activity of BSF-1 in macrophages. Results: These results suggested that BSF-1 could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell division. A total of 12,498,414 and 11,840,624 bp paired-end reads were obtained for the control group and BSF-1 group, respectively, and they corresponded to a total size of 12.5 G bp and 11.8 G bp, respectively, after the low-quality reads and adapter sequences were removed. Approximately 81.83% of the total number of genes (8,257) were expressed reads per kilobase per million mapped reads (RPKM ≥1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 group. A gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functions. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathways are significantly enriched for DEGs between the two cell groups. Conclusion: An analysis of transcriptome resources enabled us to examine gene expression profiles, verify differential gene expression, and select candidate signaling pathways as the mechanisms of the immunomodulatory activity of BSF-1. Based on the experimental data, we believe that the significant antitumor activities of BSF-1 in vivo mainly involve the MAPK signaling pathways. SUMMARY Boletus speciosus Frost-1 (BSF-1) could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell divisionApproximately 81.83% of the total number of genes (8257) were expressed (reads per kilobase per million mapped reads [RPKM] =1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 groupA gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functionsA Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase signaling pathways are significantly enriched for DEGs between the two cell groups. Abbreviations used: BSF-1: Boletus speciosus Frost polysaccharide. PMID:28839373

Music enrichment programs improve the neural encoding of speech in at-risk children.

PubMed

Kraus, Nina; Slater, Jessica; Thompson, Elaine C; Hornickel, Jane; Strait, Dana L; Nicol, Trent; White-Schwoch, Travis

2014-09-03

Musicians are often reported to have enhanced neurophysiological functions, especially in the auditory system. Musical training is thought to improve nervous system function by focusing attention on meaningful acoustic cues, and these improvements in auditory processing cascade to language and cognitive skills. Correlational studies have reported musician enhancements in a variety of populations across the life span. In light of these reports, educators are considering the potential for co-curricular music programs to provide auditory-cognitive enrichment to children during critical developmental years. To date, however, no studies have evaluated biological changes following participation in existing, successful music education programs. We used a randomized control design to investigate whether community music participation induces a tangible change in auditory processing. The community music training was a longstanding and successful program that provides free music instruction to children from underserved backgrounds who stand at high risk for learning and social problems. Children who completed 2 years of music training had a stronger neurophysiological distinction of stop consonants, a neural mechanism linked to reading and language skills. One year of training was insufficient to elicit changes in nervous system function; beyond 1 year, however, greater amounts of instrumental music training were associated with larger gains in neural processing. We therefore provide the first direct evidence that community music programs enhance the neural processing of speech in at-risk children, suggesting that active and repeated engagement with sound changes neural function. Copyright © 2014 the authors 0270-6474/14/3411913-06$15.00/0.

Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

PubMed

Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

2008-01-01

ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of predictive genomic investigations.

Trace element partitioning in fluvial tufa reveals variable portions of biologically influenced calcite precipitation

NASA Astrophysics Data System (ADS)

Ritter, Simon M.; Isenbeck-Schröter, Margot; Schröder-Ritzrau, Andrea; Scholz, Christian; Rheinberger, Stefan; Höfle, Bernhard; Frank, Norbert

2018-03-01

The formation of tufa is essentially influenced by biological processes and, in order to infer environmental information from tufa deposits, it has to be determined how the geochemistry of biologically influenced tufa deviates from equilibrium conditions between water and calcite precipitate. We investigated the evolution of the water and tufa geochemistry of consecutive tufa barrages in a small tufa-depositing creek in Southern Germany. High incorporation of divalent cations into tufa is ubiquitous, which is probably promoted by an influence of biofilms in the tufa element partitioning. The distribution coefficients for the incorporation of Mg, Sr and Ba into tufa at the Kaisinger creek D(Mg), D(Sr) and D(Ba) are 0.020-0.031, 0.13-0.18 and 0.26-0.43, respectively. This agrees with previous research suggesting that biofilm influenced tufa will be enriched in divalent cations over equilibrium values in the order of Mg < Sr < Ba. Furthermore, the incorporation of Mg, Sr and Ba into tufa of the Kaisinger creek decreases downstream, which can be attributed to changes of the relative portions of bio-influenced tufa formation with likely higher distribution coefficients and inorganically-driven tufa formation with likely lower distribution coefficients. Additionally, the distribution coefficients of metals in tufa of the Kaisinger creek D(Cd), D(Zn), D(Co) and D(Mn) show values of 11-22, 2.2-12, 0.7-4.9 and 30-57, respectively. These metals are highly enriched in upstream tufa deposits and their contents in tufa strongly decrease downstream. Such highly compatible elements could therefore be used to distinguish easily between different lateral sections in fluvial barrage-dam tufa depositional systems and could serve as a useful geochemical tool in studying ancient barrage-dam tufa depositional systems.

A post-gene silencing bioinformatics protocol for plant-defence gene validation and underlying process identification: case study of the Arabidopsis thaliana NPR1.

PubMed

Yocgo, Rosita E; Geza, Ephifania; Chimusa, Emile R; Mazandu, Gaston K

2017-11-23

Advances in forward and reverse genetic techniques have enabled the discovery and identification of several plant defence genes based on quantifiable disease phenotypes in mutant populations. Existing models for testing the effect of gene inactivation or genes causing these phenotypes do not take into account eventual uncertainty of these datasets and potential noise inherent in the biological experiment used, which may mask downstream analysis and limit the use of these datasets. Moreover, elucidating biological mechanisms driving the induced disease resistance and influencing these observable disease phenotypes has never been systematically tackled, eliciting the need for an efficient model to characterize completely the gene target under consideration. We developed a post-gene silencing bioinformatics (post-GSB) protocol which accounts for potential biases related to the disease phenotype datasets in assessing the contribution of the gene target to the plant defence response. The post-GSB protocol uses Gene Ontology semantic similarity and pathway dataset to generate enriched process regulatory network based on the functional degeneracy of the plant proteome to help understand the induced plant defence response. We applied this protocol to investigate the effect of the NPR1 gene silencing to changes in Arabidopsis thaliana plants following Pseudomonas syringae pathovar tomato strain DC3000 infection. Results indicated that the presence of a functionally active NPR1 reduced the plant's susceptibility to the infection, with about 99% of variability in Pseudomonas spore growth between npr1 mutant and wild-type samples. Moreover, the post-GSB protocol has revealed the coordinate action of target-associated genes and pathways through an enriched process regulatory network, summarizing the potential target-based induced disease resistance mechanism. This protocol can improve the characterization of the gene target and, potentially, elucidate induced defence response by more effectively utilizing available phenotype information and plant proteome functional knowledge.

Identification of candidate genes in osteoporosis by integrated microarray analysis.

PubMed

Li, J J; Wang, B Q; Fei, Q; Yang, Y; Li, D

2016-12-01

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation.Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594-601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1. © 2016 Fei et al.

An examination of conceptual change in undergraduate biology majors while learning science concepts including biological evolution

NASA Astrophysics Data System (ADS)

McQuaide, Glenn G.

2006-12-01

Without adequate understanding of science, we cannot make responsible personal, regional, national, or global decisions about any aspect of life dealing with science. Better understanding how we learn about science can contribute to improving the quality of our educational experiences. Promoting pathways leading to life-long learning and deep understanding in our world should be a goal for all educators. This dissertation project was a phenomenological investigation into undergraduate understanding and acceptance of scientific theories, including biological evolution. Specifically, student descriptions of conceptual change while learning science theory were recorded and analyzed. These qualitative investigations were preceded by a survey that provided a means of selecting students who had a firmer understanding of science theory. Background information and survey data were collected in an undergraduate biology class at a small, Southern Baptist-affiliated liberal arts school located in south central Kentucky. Responses to questions on the MATE (Rutledge and Warden, 1999) instrument were used to screen students for interviews, which investigated the way by which students came to understand and accept scientific theories. This study identifies some ways by which individuals learn complex science theories, including biological evolution. Initial understanding and acceptance often occurs by the conceptual change method described by Posner et al. (1982). Three principle ways by which an individual may reach a level of understanding and acceptance of science theory were documented in this study. They were conceptual change through application of logic and reasoning; conceptual change through modification of religious views; and conceptual change through acceptance of authoritative knowledge. Development of a deeper, richer understanding and acceptance of complex, multi-faceted concepts such as biological evolution occurs in some individuals by means of conceptual enrichment. Conceptual enrichment occurs through addition of new knowledge, and then examining prior knowledge through the perspective of this new knowledge. In the field of science, enrichment reinforces complex concepts when multiple, convergent lines of supporting evidences point to the same rational scientific conclusion.

Behavioral and Biological Effects of Housing Conditions and Stress in Male Rats - Relevance to Heart Disease

DTIC Science & Technology

2006-08-01

animals had higher corticosterone than Combined Enrichment/Not Stressed (CNS) animals (F [1, 22 ] = 6.78, p < 0.01). The greatest effects were in...biological effects of stress. In particular, plasma corticosterone levels have been reported to increase in response to stressors in different... effects of restraint stress on the biological and behavioral factors relevant to cardiovascular disease (e.g., plasma corticosterone levels

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

[Acidophilic methanogens and their applications in anaerobic digestion].

PubMed

Guo, Xiao-Hui; Wu, Wei-Xiang; Han, Zhi-Ying; Shi, De-Zhi

2011-02-01

Methanogens play an important role in global carbon cycle. There exists a range of unknown methanogenic archaea in acidic peat lands, among which, acidophilic methanogens have attracted increasing research interests because of their special metabolic characteristics. To introduce acidophilic methanogens in the anaerobic digestion process of high concentration organic wastes or waste water could essentially overcome the inhibition of acid accumulation on the methanogens and help reduce the operation cost, broadening the industrial application of anaerobic bio-treatment technology. In this paper, we reviewed the recent researches on acidophilic methanogens, with the focus on enrichment and isolation methods, physiological and biochemical characters, metabolic characteristics, and application of molecular biology. The potential applications of acidophilic methanogens in anaerobic digestion process were analyzed and proposed, and the directions for further researches were suggested.

Continuous Succinic Acid Production by Actinobacillus succinogenes on Xylose-Enriched Hydrolysate

DOE PAGES

Bradfield, Michael F. A.; Mohagheghi, Ali; Salvachua, Davinia; ...

2015-11-14

Bio-manufacturing of high-value chemicals in parallel to renewable biofuels has the potential to dramatically improve the overall economic landscape of integrated lignocellulosic biorefineries. However, this will require the generation of carbohydrate streams from lignocellulose in a form suitable for efficient microbial conversion and downstream processing appropriate to the desired end use, making overall process development, along with selection of appropriate target molecules, crucial to the integrated biorefinery. Succinic acid (SA), a high-value target molecule, can be biologically produced from sugars and has the potential to serve as a platform chemical for various chemical and polymer applications. However, the feasibility ofmore » microbial SA production at industrially relevant productivities and yields from lignocellulosic biorefinery streams has not yet been reported.« less

Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a suppressor of innate immunity in Arabidopsis thaliana.

PubMed

Zhang, Xiao-Ning; Shi, Yifei; Powers, Jordan J; Gowda, Nikhil B; Zhang, Chong; Ibrahim, Heba M M; Ball, Hannah B; Chen, Samuel L; Lu, Hua; Mount, Stephen M

2017-10-11

Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45-1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45-1 plants do indeed show enhanced immunity. We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides.

PubMed

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-21

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.

Confronting the Paradox of Enrichment to the Metacommunity Perspective

PubMed Central

Hauzy, Céline; Nadin, Grégoire; Canard, Elsa; Gounand, Isabelle; Mouquet, Nicolas; Ebenman, Bo

2013-01-01

Resource enrichment can potentially destabilize predator-prey dynamics. This phenomenon historically referred as the "paradox of enrichment" has mostly been explored in spatially homogenous environments. However, many predator-prey communities exchange organisms within spatially heterogeneous networks called metacommunities. This heterogeneity can result from uneven distribution of resources among communities and thus can lead to the spreading of local enrichment within metacommunities. Here, we adapted the original Rosenzweig-MacArthur predator-prey model, built to study the paradox of enrichment, to investigate the effect of regional enrichment and of its spatial distribution on predator-prey dynamics in metacommunities. We found that the potential for destabilization was depending on the connectivity among communities and the spatial distribution of enrichment. In one hand, we found that at low dispersal regional enrichment led to the destabilization of predator-prey dynamics. This destabilizing effect was more pronounced when the enrichment was uneven among communities. In the other hand, we found that high dispersal could stabilize the predator-prey dynamics when the enrichment was spatially heterogeneous. Our results illustrate that the destabilizing effect of enrichment can be dampened when the spatial scale of resource enrichment is lower than that of organismss movements (heterogeneous enrichment). From a conservation perspective, our results illustrate that spatial heterogeneity could decrease the regional extinction risk of species involved in specialized trophic interactions. From the perspective of biological control, our results show that the heterogeneous distribution of pest resource could favor or dampen outbreaks of pests and of their natural enemies, depending on the spatial scale of heterogeneity. PMID:24358242

Enrichment of reticulocytes from whole blood using aqueous multiphase systems of polymers.

PubMed

Kumar, Ashok A; Lim, Caeul; Moreno, Yovany; Mace, Charles R; Syed, Abeer; Van Tyne, Daria; Wirth, Dyann F; Duraisingh, Manoj T; Whitesides, George M

2015-01-01

This paper demonstrates the enrichment of reticulocytes by centrifuging whole blood through aqueous multiphase systems (AMPSs)-immiscible phases of solutions of polymers that form step-gradients in density. The interfaces of an AMPS concentrate cells; this concentration facilitates the extraction of blood enriched for reticulocytes. AMPS enrich reticulocytes from blood from both healthy and hemochromatosis donors. Varying the osmolality and density of the phases of AMPS provides different levels of enrichment and yield of reticulocytes. A maximum enrichment of reticulocytemia of 64 ± 3% was obtained from donors with hemochromatosis. When used on peripheral blood from normal donors, AMPS can provide a higher yield of enriched reticulocytes and a higher proportion of reticulocytes expressing CD71 than differential centrifugation followed by centrifugation over Percoll. Blood enriched for reticulocytes by AMPS could be useful for research on malaria. Several species of malaria parasites show a preference to invade young erythrocytes and reticulocytes; this preference complicates in vitro cultivation of these species in human blood. Plasmodium knowlesi malaria parasites invade normal human blood enriched for reticulocytes by AMPSs at a rate 2.2 times greater (P < 0.01) than they invade unenriched blood. Parasite invasion in normal blood enriched by AMPS was 1.8 times greater (P < 0.05) than in blood enriched to a similar reticulocytemia by differential centrifugation followed by centrifugation over Percoll. The enrichment of reticulocytes that are invaded by malaria parasites demonstrates that AMPSs can provide a label-free method to enrich cells for biological research. © 2014 Wiley Periodicals, Inc.

m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

PubMed Central

Cui, Qi; Shi, Hailing; Ye, Peng; Li, Li; Qu, Qiuhao; Sun, Guoqiang; Sun, Guihua; Lu, Zhike; Huang, Yue; Yang, Cai-Guang; Riggs, Arthur D.

2017-01-01

Summary RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma. PMID:28297667

Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease

PubMed Central

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre FR; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2016-01-01

Objective Genome-wide association (GWA) studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Employing pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CADGWAS data sets (9,889 cases/11,089 controls), nominally significant gene-sets were tested for replication in a meta-analysis of 9 additional studies (15,502 cases/55,730 controls) from the CARDIoGRAM Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication p<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix integrity, innate immunity, axon guidance, and signaling by PDRF, NOTCH, and the TGF-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (e.g. semaphorin regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared to random networks (p<0.001). Network centrality analysis (‘degree’ and ‘betweenness’) further identified genes (e.g. NCAM1, FYN, FURIN etc.) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. PMID:25977570

Purification of Plant Receptor Kinases from Plant Plasma Membranes.

PubMed

Lee, Jin Suk

2017-01-01

Receptor kinases play a central role in various biological processes, but due to their low abundance and highly hydrophobic and dynamic nature, only a few of them have been functionally characterized, and their partners and ligands remain unidentified. Receptor protein extraction and purification from plant tissues is one of the most challenging steps for the success of various biochemical analyses to characterize their function. Immunoprecipitation is a widely used and selective method for enriching or purifying a specific protein. Here we describe two different optimized protein purification protocols, batch and on-chip immunoprecipitation, which efficiently isolate plant membrane receptor kinases for functional analysis.

Enhanced phenol removal in an innovative lignite activated coke-assisted biological process.

PubMed

Zhang, Chen; Li, Jianfeng; Cheng, Fangqin; Liu, Yu

2018-07-01

In this study, a lignite activated coke (LAC)-assisted activated sludge (AS) process was developed for enhancing biodegradation of phenol, while the effects of LAC on sludge properties and microbial community structure were investigated. It was found that more than 90% of phenol was removed within 1 h in the LAC/AS, which was 3 times higher than the conventional AS process. Moreover, the floc size and settleability were also significantly improved in the LAC/AS. These results suggested that LAC could serve as the nucleating agent to promote the formation of compact floc, which was beneficial for toxicity mitigation and system stability. The microbial community analysis by 16S high-throughput pyrosequencing technology further revealed a more abundant bacterial richness and diversity in the LAC/AS process loaded with phenol, while some phenol degraders, such as Propionibacteriaceae were enriched. Engineering implications further suggests the LAC-assisted AS process is technically sound and economically viable. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biology...Its People and Its Papers.

ERIC Educational Resources Information Center

Baumel, Howard B.; Berger, J. Joel

This publication contains a collection of research papers designed to be used as a supplement to the textbook in a high school biology class. The material can be used to enrich the curriculum by stimulating critical thinking and by making high school students aware of the ways in which scientists work. Some of the papers have been condensed or…

Room-temperature synthesis of core-shell structured magnetic covalent organic frameworks for efficient enrichment of peptides and simultaneous exclusion of proteins.

PubMed

Lin, Guo; Gao, Chaohong; Zheng, Qiong; Lei, Zhixian; Geng, Huijuan; Lin, Zian; Yang, Huanghao; Cai, Zongwei

2017-03-28

Core-shell structured magnetic covalent organic frameworks (Fe 3 O 4 @COFs) were synthesized via a facile approach at room temperature. Combining the advantages of high porosity, magnetic responsiveness, chemical stability and selectivity, Fe 3 O 4 @COFs can serve as an ideal absorbent for the highly efficient enrichment of peptides and the simultaneous exclusion of proteins from complex biological samples.

Enrichment and proteomic analysis of plasma membrane from rat dorsal root ganglions

PubMed Central

2009-01-01

Background Dorsal root ganglion (DRG) neurons are primary sensory neurons that conduct neuronal impulses related to pain, touch and temperature senses. Plasma membrane (PM) of DRG cells plays important roles in their functions. PM proteins are main performers of the functions. However, mainly due to the very low amount of DRG that leads to the difficulties in PM sample collection, few proteomic analyses on the PM have been reported and it is a subject that demands further investigation. Results By using aqueous polymer two-phase partition in combination with high salt and high pH washing, PMs were efficiently enriched, demonstrated by western blot analysis. A total of 954 non-redundant proteins were identified from the plasma membrane-enriched preparation with CapLC-MS/MS analysis subsequent to protein separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or shotgun digestion. 205 (21.5%) of the identified proteins were unambiguously assigned as PM proteins, including a large number of signal proteins, receptors, ion channel and transporters. Conclusion The aqueous polymer two-phase partition is a simple, rapid and relatively inexpensive method. It is well suitable for the purification of PMs from small amount of tissues. Therefore, it is reasonable for the DRG PM to be enriched by using aqueous two-phase partition as a preferred method. Proteomic analysis showed that DRG PM was rich in proteins involved in the fundamental biological processes including material exchange, energy transformation and information transmission, etc. These data would help to our further understanding of the fundamental DRG functions. PMID:19889238

Metagenomic mining pectinolytic microbes and enzymes from an apple pomace-adapted compost microbial community.

PubMed

Zhou, Man; Guo, Peng; Wang, Tao; Gao, Lina; Yin, Huijun; Cai, Cheng; Gu, Jie; Lü, Xin

2017-01-01

Degradation of pectin in lignocellulosic materials is one of the key steps for biofuel production. Biological hydrolysis of pectin, i.e., degradation by pectinolytic microbes and enzymes, is an attractive paradigm because of its obvious advantages, such as environmentally friendly procedures, low in energy demand for lignin removal, and the possibility to be integrated in consolidated process. In this study, a metagenomics sequence-guided strategy coupled with enrichment culture technique was used to facilitate targeted discovery of pectinolytic microbes and enzymes. An apple pomace-adapted compost (APAC) habitat was constructed to boost the enrichment of pectinolytic microorganisms. Analyses of 16S rDNA high-throughput sequencing revealed that microbial communities changed dramatically during composting with some bacterial populations being greatly enriched. Metagenomics data showed that apple pomace-adapted compost microbial community (APACMC) was dominated by Proteobacteria and Bacteroidetes . Functional analysis and carbohydrate-active enzyme profiles confirmed that APACMC had been successfully enriched for the targeted functions. Among the 1756 putative genes encoding pectinolytic enzymes, 129 were predicted as novel (with an identity <30% to any CAZy database entry) and only 1.92% were more than 75% identical with proteins in NCBI environmental database, demonstrating that they have not been observed in previous metagenome projects. Phylogenetic analysis showed that APACMC harbored a broad range of pectinolytic bacteria and many of them were previously unrecognized. The immensely diverse pectinolytic microbes and enzymes found in our study will expand the arsenal of proficient degraders and enzymes for lignocellulosic biofuel production. Our study provides a powerful approach for targeted mining microbes and enzymes in numerous industries.

Assessment of the Interstellar Processes Leading to Deuterium Enrichment in Meteoritic Organics

NASA Technical Reports Server (NTRS)

Sandford, Scott A.; Bernstein, Max P.; Dworkin, Jason P.; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

The presence of isotopic anomalies is the most unequivocal demonstration that meteoritic material contains circumstellar or interstellar components. In the case of organic compounds in meteorites and interplanetary dust particles (IDPs), the most useful isotopic tracer has been deuterium (D). We discuss four processes that are expected to lead to D enrichment in interstellar materials and describe how their unique characteristics can be used to assess their relative importance for the organics in meteorites. These enrichment processes are low temperature gas phase ion-molecule reactions, low temperature gas-grain reactions, gas phase unimolecular photodissociation, and ultraviolet photolysis in D-enriched ice mantles. Each of these processes is expected to be associated with distinct regiochemical signatures (D placement on the product molecules, correlation with specific chemical functionalities, etc.), especially in the molecular population of polycyclic aromatic hydrocarbons (PAHs). We describe these differences and discuss how they may be used to delineate the various interstellar processes that may have contributed to meteoritic D enrichments. We also briefly discuss how these processes may affect the isotopic distributions in C, 0, and N in the same compounds.

Population resequencing reveals candidate genes associated with salinity adaptation of the Pacific oyster Crassostrea gigas.

PubMed

She, Zhicai; Li, Li; Meng, Jie; Jia, Zhen; Que, Huayong; Zhang, Guofan

2018-06-06

The Pacific oyster Crassostrea gigas is an important cultivated shellfish. As a euryhaline species, it has evolved adaptive mechanisms responding to the complex and changeable intertidal environment that it inhabits. To investigate the genetic basis of this salinity adaptation mechanism, we conducted a genome-wide association study using phenotypically differentiated populations (hyposalinity and hypersalinity adaptation populations, and control population), and confirmed our results using an independent population, high-resolution melting, and mRNA expression analysis. For the hyposalinity adaptation, we determined 24 genes, including Cg_CLCN7 (chloride channel protein 7) and Cg_AP1 (apoptosis 1 inhibitor), involved in the ion/water channel and transporter mechanisms, free amino acid and reactive oxygen species metabolism, immune responses, and chemical defence. Three SNPs located on these two genes were significantly differentiated between groups, as was Cg_CLCN7. For the hypersalinity adaptation, the biological process for positive regulating the developmental process was enriched. Enriched gene functions were focused on transcriptional regulation, signal transduction, and cell growth and differentiation, including calmodulin (Cg_CaM) and ficolin-2 (Cg_FCN2). These genes and polymorphisms possibly play an important role in oyster hyposalinity and hypersalinity adaptation. They not only further our understanding of salinity adaptation mechanisms but also provide markers for highly adaptable oyster strains suitable for breeding.

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Phillips, Charles A; Langston, Michael A; Ragan, Mark A

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k ) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k . Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k .

MicroRNAs in Honey Bee Caste Determination

PubMed Central

Ashby, Regan; Forêt, Sylvain; Searle, Iain; Maleszka, Ryszard

2016-01-01

The cellular mechanisms employed by some organisms to produce contrasting morphological and reproductive phenotypes from the same genome remains one of the key unresolved issues in biology. Honeybees (Apis mellifera) use differential feeding and a haplodiploid sex determination system to generate three distinct organismal outcomes from the same genome. Here we investigate the honeybee female and male caste-specific microRNA and transcriptomic molecular signatures during a critical time of larval development. Both previously undetected and novel miRNAs have been discovered, expanding the inventory of these genomic regulators in invertebrates. We show significant differences in the microRNA and transcriptional profiles of diploid females relative to haploid drone males as well as between reproductively distinct females (queens and workers). Queens and drones show gene enrichment in physio-metabolic pathways, whereas workers show enrichment in processes associated with neuronal development, cell signalling and caste biased structural differences. Interestingly, predicted miRNA targets are primarily associated with non-physio-metabolic genes, especially neuronal targets, suggesting a mechanistic disjunction from DNA methylation that regulates physio-metabolic processes. Accordingly, miRNA targets are under-represented in methylated genes. Our data show how a common set of genetic elements are differentially harnessed by an organism, which may provide the remarkable level of developmental flexibility required. PMID:26739502

Demonstration and Characterization of Biomolecular Enrichment on Microfluidic Aptamer-Functionalized Surfaces

PubMed Central

Nguyen, Thai Huu; Pei, Renjun; Stojanovic, Milan; Lin, Qiao

2010-01-01

This paper demonstrates and systematically characterizes the enrichment of biomolecular compounds using aptamer-functionalized surfaces within a microfluidic device. The device consists of a microchamber packed with aptamer-functionalized microbeads and integrated with a microheater and temperature sensor to enable thermally controlled binding and release of biomolecules by the aptamer. We first present an equilibrium binding-based analytical model to understand the enrichment process. The characteristics of the aptamer-analyte binding and enrichment are then experimentally studied, using adenosine monophosphate (AMP) and a specific RNA aptamer as a model system. The temporal process of AMP binding to the aptamer is found to be primarily determined by the aptamer-AMP binding kinetics. The temporal process of aptamer-AMP dissociation at varying temperatures is also obtained and observed to occur relatively rapidly (< 2 s). The specificity of the enrichment is next confirmed by performing selective enrichment of AMP from a sample containing biomolecular impurities. Finally, we investigate the enrichment of AMP by either discrete or continuous introduction of a dilute sample into the microchamber, demonstrating enrichment factors ranging from 566 to 686×, which agree with predictions of the analytical model. PMID:21765612

Coupling flash liquid chromatography with mass spectrometry for enrichment and isolation of milk oligosaccharides for functional studies.

PubMed

Strum, John S; Aldredge, Danielle; Barile, Daniela; Lebrilla, Carlito B

2012-05-15

Mass spectrometry has been coupled with flash liquid chromatography to yield new capabilities for isolating nonchromophoric material from complicated biological mixtures. A flash liquid chromatography/tandem mass spectrometry (LC/MS/MS) method enabled fraction collection of milk oligosaccharides from biological mixtures based on composition and structure. The method is compatible with traditional gas pressure-driven flow flash chromatography widely employed in organic chemistry laboratories. The online mass detector enabled real-time optimization of chromatographic parameters to favor separation of oligosaccharides that would otherwise be indistinguishable from coeluting components with a nonspecific detector. Unlike previously described preparative LC/MS techniques, we have employed a dynamic flow connection that permits any flow rate from the flash system to be delivered from 1 to 200 ml/min without affecting the ionization conditions of the mass spectrometer. A new way of packing large amounts of graphitized carbon allowed the enrichment and separation of milligram quantities of structurally heterogeneous mixtures of human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). Abundant saccharide components in milk, such as lactose and lacto-N-tetraose, were separated from the rarer and less abundant oligosaccharides that have greater structural diversity and biological functionality. Neutral and acidic HMOs and BMOs were largely separated and enriched with a dual binary solvent system. Published by Elsevier Inc.

D and 18O enrichment measurements in biological fluids in a continuous-flow elemental analyser with an isotope-ratio mass spectrometer using two configurations.

PubMed

Ripoche, N; Ferchaud-Roucher, V; Krempf, M; Ritz, P

2006-09-01

In doubly labelled water studies, biological sample enrichments are mainly measured using off-line techniques (equilibration followed by dual-inlet introduction) or high-temperature elemental analysis (HT-EA), coupled with an isotope-ratio mass spectrometer (IRMS). Here another continuous-flow method, (CF-EA/IRMS), initially dedicated to water, is tested for plasma and urine analyses. The elemental analyser configuration is adapted for each stable isotope: chromium tube for deuterium reduction and glassy carbon reactor for 18O pyrolysis. Before on-line conversion of water into gas, each matrix is submitted to a short and easy treatment, which is the same for the analysis of the two isotopes. Plasma is passed through centrifugal filters. Urine is cleaned with black carbon and filtered (0.45 microm diameter). Tested between 150 and 300 ppm in these fluids, the D/H ratio response is linear with good repeatability (SD<0.2 ppm) and reproducibility (SD<0.5 ppm). For 18O/16O ratios (from 2000 to 2200 ppm), the same repeatability is obtained with a between-day precision lower than 1.4 ppm. The accuracy on biological samples is validated by comparison to classical dual-inlet methods: 18O analyses give more accurate results. The data show that enriched physiological fluids can be successfully analysed in CF-EA/IRMS. Copyright (c) 2006 John Wiley & Sons, Ltd.

Convergent genetic and expression data implicate immunity in Alzheimer's disease

PubMed Central

Jones, Lesley; Lambert, Jean-Charles; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Vedernikov, Alexey; Escott-Price, Valentina; Stone, Timothy; Richards, Alexander; Bellenguez, Céline; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Gerrish, Amy; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letteneur, Luc; Kornhuber, Johanes; Tárraga, Lluís; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Emilsson, Valur; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Kehoe, Pat; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleὀ, Alberti; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick; Hardy, John; Naranjo, Maria Candida Deniz; Razquin, Cristina; Bosco, Paola; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Moebus, Susanne; Mecocci, Patrizia; del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Jessen, Frank; Dichgans, Martin; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alavarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee FAG; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John SK; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Pastor, Pau; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broekhoven, Christine; Ramirez, Alfredo; Schellenberg, Gerard D; Seshadri, Sudha; Amouyel, Philippe; Holmans, Peter A

2015-01-01

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics. PMID:25533204

Sex Differences in Panic-Relevant Responding to a 10% Carbon Dioxide-Enriched Air Biological Challenge

PubMed Central

Nillni, Yael I.; Berenz, Erin C.; Rohan, Kelly J.; Zvolensky, Michael J.

2011-01-01

The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; Mage = 23.2 years, SD = 8.9) who underwent a 4-minute 10% CO2-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically-relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. PMID:22115836

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Convergent genetic and expression data implicate immunity in Alzheimer's disease.

PubMed

2015-06-01

Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. Copyright © 2015. Published by Elsevier Inc.

Supporting read-across using biological data.

PubMed

Zhu, Hao; Bouhifd, Mounir; Donley, Elizabeth; Egnash, Laura; Kleinstreuer, Nicole; Kroese, E Dinant; Liu, Zhichao; Luechtefeld, Thomas; Palmer, Jessica; Pamies, David; Shen, Jie; Strauss, Volker; Wu, Shengde; Hartung, Thomas

2016-01-01

Read-across, i.e. filling toxicological data gaps by relating to similar chemicals, for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, however, biological similarity based on biological data adds extra strength to this process. In the context of developing Good Read-Across Practice guidance, a number of case studies were evaluated to demonstrate the use of biological data to enrich read-across. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of e.g. genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances become increasingly available enabling big data approaches in read-across studies. Several case studies using various big data sources are described in this paper. An example is given for the US EPA's ToxCast dataset allowing read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example for REACH registration data enhancing read-across for acute toxicity studies is given. A different approach is taken using omics data to establish biological similarity: Examples are given for stem cell models in vitro and short-term repeated dose studies in rats in vivo to support read-across and category formation. These preliminary biological data-driven read-across studies highlight the road to the new generation of read-across approaches that can be applied in chemical safety assessment.

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PubMed Central

Loughman, James; Wildsoet, Christine F.; Williams, Cathy; Guggenheim, Jeremy A.

2018-01-01

Purpose To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. Results Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469). Conclusions Common genetic variants within or nearby genes that cause syndromic myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis of syndromic forms of refractive errors can provide new insights into the etiology of myopia and additional potential targets for therapeutic interventions. PMID:29346494

Effects of sludge retention time, carbon and initial biomass concentrations on selection process: From activated sludge to polyhydroxyalkanoate accumulating cultures.

PubMed

Chen, Zhiqiang; Huang, Long; Wen, Qinxue; Zhang, Huichao; Guo, Zirui

2017-02-01

Four sequence batch reactors (SBRs) fed by fermented sugar cane wastewater were continuously operated under the aerobic dynamic feeding (ADF) mode with different configurations of sludge retention time (SRT), carbon and initial biomass concentrations to enrich polyhydroxyalkanoate (PHA) accumulating mixed microbial cultures (MMCs) from municipal activated sludge. The stability of SBRs was investigated besides the enrichment performance. The microbial community structures of the enriched MMCs were analyzed using terminal restriction fragment length polymorphism (T-RFLP). The optimum operating conditions for the enrichment process were: SRT of 5days, carbon concentration of 2.52g COD/L and initial biomass concentration of 3.65g/L. The best enrichment performance in terms of both operating stability and PHA storage ability of enriched cultures (with the maximum PHA content and PHA storage yield (Y PHA/S ) of 61.26% and 0.68mg COD/mg COD, respectively) was achieved under this condition. Effects of the SRT, carbon concentration and initial biomass concentration on the PHA accumulating MMCs selection process were discussed respectively. A new model including the segmentation of the enrichment process and the effects of SRT on each phase was proposed. Copyright © 2016. Published by Elsevier B.V.

NaviSE: superenhancer navigator integrating epigenomics signal algebra.

PubMed

Ascensión, Alex M; Arrospide-Elgarresta, Mikel; Izeta, Ander; Araúzo-Bravo, Marcos J

2017-06-06

Superenhancers are crucial structural genomic elements determining cell fate, and they are also involved in the determination of several diseases, such as cancer or neurodegeneration. Although there are pipelines which use independent pieces of software to predict the presence of superenhancers from genome-wide chromatin marks or DNA-interaction protein binding sites, there is not yet an integrated software tool that processes automatically algebra combinations of raw data sequencing into a comprehensive final annotated report of predicted superenhancers. We have developed NaviSE, a user-friendly streamlined tool which performs a fully-automated parallel processing of genome-wide epigenomics data from sequencing files into a final report, built with a comprehensive set of annotated files that are navigated through a graphic user interface dynamically generated by NaviSE. NaviSE also implements an 'epigenomics signal algebra' that allows the combination of multiple activation and repression epigenomics signals. NaviSE provides an interactive chromosomal landscaping of the locations of superenhancers, which can be navigated to obtain annotated information about superenhancer signal profile, associated genes, gene ontology enrichment analysis, motifs of transcription factor binding sites enriched in superenhancers, graphs of the metrics evaluating the superenhancers quality, protein-protein interaction networks and enriched metabolic pathways among other features. We have parallelised the most time-consuming tasks achieving a reduction up to 30% for a 15 CPUs machine. We have optimized the default parameters of NaviSE to facilitate its use. NaviSE allows different entry levels of data processing, from sra-fastq files to bed files; and unifies the processing of multiple replicates. NaviSE outperforms the more time-consuming processes required in a non-integrated pipeline. Alongside its high performance, NaviSE is able to provide biological insights, predicting cell type specific markers, such as SOX2 and ZIC3 in embryonic stem cells, CDK5R1 and REST in neurons and CD86 and TLR2 in monocytes. NaviSE is a user-friendly streamlined solution for superenhancer analysis, annotation and navigation, requiring only basic computer and next generation sequencing knowledge. NaviSE binaries and documentation are available at: https://sourceforge.net/projects/navise-superenhancer/ .

SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, J; Deasy, J; Kerns, S

Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation).more » To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques enabled designing better models and identifying more plausible biological processes associated with the outcomes.« less

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

PubMed Central

Kuleshov, Maxim V.; Jones, Matthew R.; Rouillard, Andrew D.; Fernandez, Nicolas F.; Duan, Qiaonan; Wang, Zichen; Koplev, Simon; Jenkins, Sherry L.; Jagodnik, Kathleen M.; Lachmann, Alexander; McDermott, Michael G.; Monteiro, Caroline D.; Gundersen, Gregory W.; Ma'ayan, Avi

2016-01-01

Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr. PMID:27141961

Size-Based Enrichment Technologies for Non-cancerous Tumor-Derived Cells in Blood.

PubMed

Mong, Jamie; Tan, Min-Han

2018-05-01

Enumeration of circulating tumor cells (CTCs) in the bloodstream can predict prognosis and survival in cancer patients. However, CTC rarity and heterogeneity pose challenges in using them as biomarkers. Recent publications have reported new classes of circulating, non-cancerous tumor-derived cells present in cancer patients but not in healthy controls; these include cancer-associated macrophages, tumor-endothelial clusters (TECs), and cancer-associated fibroblasts (CAFs). Well-established marker-dependent CTC enrichment technologies will miss this group of circulating cells. To maximize our chance of finding useful circulating biomarkers in cancer patients, we propose the use of size-based enrichment technologies to isolate both cancerous and non-cancerous cells in circulation. We review their biological properties and discuss device features to consider in their enrichment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Facile synthesis of titanium (IV) ion immobilized adenosine triphosphate functionalized silica nanoparticles for highly specific enrichment and analysis of intact phosphoproteins.

PubMed

Wang, Hao; Tian, Zhixin

2018-06-06

Analysis of phosphoproteins always faces the challenge of low stoichiometry, which demands highly selective and efficient enrichment in the initial sample preparation. Here we report our synthesis of the novel titanium (IV) ion immobilized adenosine triphosphate functionalized silica nanoparticles (Ti 4+ -ATP-NPs) for efficient enrichment of intact phosphoproteins. The average diameter of Ti 4+ -ATP-NPs was about 128 nm with good dispersibility and the saturated adsorption capacity for β-casein was 1046.5 mg/g. In addition, Ti 4+ -ATP-NPs exhibited high specificity and selectivity in enriching phosphoproteins from both standard protein mixtures and complex biological samples (non-fat milk, chicken egg white and mouse heart tissue extract) as demonstrated by SDS-PAGE. Copyright © 2018 Elsevier B.V. All rights reserved.

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth

PubMed Central

Carabetta, Valerie J.; Greco, Todd M.; Tanner, Andrew W.

2016-01-01

ABSTRACT Nε-Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. IMPORTANCE The past decade highlighted Nε-lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth. PMID:27376153

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth.

PubMed

Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W; Cristea, Ileana M; Dubnau, David

2016-05-01

N ε -Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. The past decade highlighted N ε -lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis . To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth.

Carbon-Isotopic Dynamics of Streams, Taylor Valley, Antarctica: Biological Effects

NASA Technical Reports Server (NTRS)

Neumann, K.; DesMarais, D. J.

1998-01-01

We have investigated the role of biological processes in the C-isotopic dynamics of the aquatic ecosystems in Taylor Valley, Antarctica. This cold desert ecosystem is characterized by the complete lack of vascular plants, and the presence of algal mats in ephemeral streams and perennially ice covered lakes. Streams having abundant algal mats and mosses have very low sigma CO2 concentrations, as well as the most depleted delta C-13 values (-4%). Previous work has shown that algal mats in these streams have delta C-13 values averaging -7.01%. These values are similar to those observed in the algal mats in shallow areas of the lakes in Taylor Valley, where CO2 is thought to be colimiting to growth. These low Sigma CO2 concentrations, and delta C(13) signatures heavier than the algal mats, suggest that CO2 may be colimiting in the streams, as well. Streams with little algal growth, especially the longer ones in Fryxell Basin, have higher Sigma CO2 concentrations and much more enriched isotopic signatures (as high as +8%). In these streams, the dissolution of isotopically enriched, cryogenic CaCO3 is probably the major source of dissolved carbonate. The delta C(13) geochemistry of Antarctic streams is radically different from the geochemistry of more temperate streams, as it is not affected by terrestrially produced, isotopically depleted Sigma CO2. These results have important implications for the understanding of "biogenic" carbonate that might have been produced from aquatic ecosystems in the past on Mars.

Whole-Genome Resequencing of Experimental Populations Reveals Polygenic Basis of Egg-Size Variation in Drosophila melanogaster.

PubMed

Jha, Aashish R; Miles, Cecelia M; Lippert, Nodia R; Brown, Christopher D; White, Kevin P; Kreitman, Martin

2015-10-01

Complete genome resequencing of populations holds great promise in deconstructing complex polygenic traits to elucidate molecular and developmental mechanisms of adaptation. Egg size is a classic adaptive trait in insects, birds, and other taxa, but its highly polygenic architecture has prevented high-resolution genetic analysis. We used replicated experimental evolution in Drosophila melanogaster and whole-genome sequencing to identify consistent signatures of polygenic egg-size adaptation. A generalized linear-mixed model revealed reproducible allele frequency differences between replicated experimental populations selected for large and small egg volumes at approximately 4,000 single nucleotide polymorphisms (SNPs). Several hundred distinct genomic regions contain clusters of these SNPs and have lower heterozygosity than the genomic background, consistent with selection acting on polymorphisms in these regions. These SNPs are also enriched among genes expressed in Drosophila ovaries and many of these genes have well-defined functions in Drosophila oogenesis. Additional genes regulating egg development, growth, and cell size show evidence of directional selection as genes regulating these biological processes are enriched for highly differentiated SNPs. Genetic crosses performed with a subset of candidate genes demonstrated that these genes influence egg size, at least in the large genetic background. These findings confirm the highly polygenic architecture of this adaptive trait, and suggest the involvement of many novel candidate genes in regulating egg size. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

A pharmacology guided approach for setting limits on product-related impurities for bispecific antibody manufacturing.

PubMed

Rajan, Sharmila; Sonoda, Junichiro; Tully, Timothy; Williams, Ambrose J; Yang, Feng; Macchi, Frank; Hudson, Terry; Chen, Mark Z; Liu, Shannon; Valle, Nicole; Cowan, Kyra; Gelzleichter, Thomas

2018-04-13

bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product. The aim of the current study was to determine acceptable levels of product-related impurities for bFKB1. To determine the tolerable levels of these impurities, we dosed obese mice with bFKB1 enriched with various levels of either HMW impurities or anti-FGFR1-related impurities, and measured biomarkers for KLB-independent FGFR1 signaling. Here, we show that product-related impurities of bFKB1, in particular, high molecular weight (HMW) impurities and anti-FGFR1-related impurities, when purposefully enriched, stimulate FGFR1 in a KLB-independent manner. By taking this approach, the tolerable levels of product-related impurities were successfully determined. Our study demonstrates a general pharmacology-guided approach to setting a product specification for a bispecific antibody whose homomultimer-related impurities could lead to undesired biological effects. Copyright © 2018. Published by Elsevier Inc.

Cellular processes involved in human epidermal cells exposed to extremely low frequency electric fields.

PubMed

Collard, J-F; Hinsenkamp, M

2015-05-01

We observed on different tissues and organisms a biological response after exposure to pulsed low frequency and low amplitude electric or electromagnetic fields but the precise mechanism of cell response remains unknown. The aim of this publication is to understand, using bioinformatics, the biological relevance of processes involved in the modification of gene expression. The list of genes analyzed was obtained after microarray protocol realized on cultures of human epidermal explants growing on deepidermized human skin exposed to a pulsed low frequency electric field. The directed acyclic graph on a WebGestalt Gene Ontology module shows six categories under the biological process root: "biological regulation", "cellular process", "cell proliferation", "death", "metabolic process" and "response to stimulus". Enriched derived categories are coherent with the type of in vitro culture, the stimulation protocol or with the previous results showing a decrease of cell proliferation and an increase of differentiation. The Kegg module on WebGestalt has highlighted "cell cycle" and "p53 signaling pathway" as significantly involved. The Kegg website brings out interactions between FoxO, MAPK, JNK, p53, p38, PI3K/Akt, Wnt, mTor or NF-KappaB. Some genes expressed by the stimulation are known to have an exclusive function on these pathways. Analyses performed with Pathway Studio linked cell proliferation, cell differentiation, apoptosis, cell cycle, mitosis, cell death etc. with our microarrays results. Medline citation generated by the software and the fold change variation confirms a diminution of the proliferation, activation of the differentiation and a less well-defined role of apoptosis or wound healing. Wnt and DKK functional classes, DKK1, MACF1, ATF3, MME, TXNRD1, and BMP-2 genes proposed in previous publications after a manual analysis are also highlighted with other genes after Pathway Studio automatic procedure. Finally, an analysis conducted on a list of genes characterized by an accelerated regulation after extremely low frequency pulsed stimulation also confirms their role in the processes of cell proliferation and differentiation. Bioinformatics approach allows in-depth research, without the bias of pre-selection, on cellular processes involved in a huge gene list. Copyright © 2015 Elsevier Inc. All rights reserved.

CHRONOS: a time-varying method for microRNA-mediated subpathway enrichment analysis.

PubMed

Vrahatis, Aristidis G; Dimitrakopoulou, Konstantina; Balomenos, Panos; Tsakalidis, Athanasios K; Bezerianos, Anastasios

2016-03-15

In the era of network medicine and the rapid growth of paired time series mRNA/microRNA expression experiments, there is an urgent need for pathway enrichment analysis methods able to capture the time- and condition-specific 'active parts' of the biological circuitry as well as the microRNA impact. Current methods ignore the multiple dynamical 'themes'-in the form of enriched biologically relevant microRNA-mediated subpathways-that determine the functionality of signaling networks across time. To address these challenges, we developed time-vaRying enriCHment integrOmics Subpathway aNalysis tOol (CHRONOS) by integrating time series mRNA/microRNA expression data with KEGG pathway maps and microRNA-target interactions. Specifically, microRNA-mediated subpathway topologies are extracted and evaluated based on the temporal transition and the fold change activity of the linked genes/microRNAs. Further, we provide measures that capture the structural and functional features of subpathways in relation to the complete organism pathway atlas. Our application to synthetic and real data shows that CHRONOS outperforms current subpathway-based methods into unraveling the inherent dynamic properties of pathways. CHRONOS is freely available at http://biosignal.med.upatras.gr/chronos/ tassos.bezerianos@nus.edu.sg Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Stable carbon isotope fractionation during bacterial acetylene fermentation: Potential for life detection in hydrocarbon-rich volatiles of icy planet(oid)s

USGS Publications Warehouse

Miller, Laurence; Baesman, Shaun; Oremland, Ron

2015-01-01

We report the first study of stable carbon isotope fractionation during microbial fermentation of acetylene (C2H2) in sediments, sediment enrichments, and bacterial cultures. Kinetic isotope effects (KIEs) averaged 3.7 ± 0.5‰ for slurries prepared with sediment collected at an intertidal mudflat in San Francisco Bay and 2.7 ± 0.2‰ for a pure culture of Pelobacter sp. isolated from these sediments. A similar KIE of 1.8 ± 0.7‰ was obtained for methanogenic enrichments derived from sediment collected at freshwater Searsville Lake, California. However, C2H2 uptake by a highly enriched mixed culture (strain SV7) obtained from Searsville Lake sediments resulted in a larger KIE of 9.0 ± 0.7‰. These are modest KIEs when compared with fractionation observed during oxidation of C1 compounds such as methane and methyl halides but are comparable to results obtained with other C2compounds. These observations may be useful in distinguishing biologically active processes operating at distant locales in the Solar System where C2H2 is present. These locales include the surface of Saturn's largest moon Titan and the vaporous water- and hydrocarbon-rich jets emanating from Enceladus.

Synthesis of Thermally Switchable Chromatographic Materials with Immobilized Ti4+ for Enrichment of Phosphopeptides by Reversible Addition Fragmentation Chain Transfer Polymerization

NASA Astrophysics Data System (ADS)

Wang, Di; Cao, Zhihan; Pang, Xinzhu; Deng, Yulin; Li, Bo; Dai, Rongji

2018-01-01

Reversible phosphorylation of proteins is one of the most crucial types of post-translational modifications (PTMs). And it shows significant work in diversified biological processes. However, the separation technology of phosphorylated peptides is still an analytical challenge in phosphoproteomics, because phosphopeptides are alway in low stoichiometry. Thus, enrichment of phosphopeptides before detection is indispensable. In this study, a novel temperature regulated separation protocol was developed. Silica@p (NIPAAm-co-IPPA)-Ti4+, a new Ti(IV)-IMAC (Immobilized Metal Affinity chromatography) materials was synthesized by reversible addition fragmentation chain transfer polymerization (RAFT). By the unique thermally responsive properties of poly(N-isopropylacrylamide) (PNIPAAm), the captured phosphorylated peptides could be released by changing temperature only without applying any other eluant which could damage the phosphopeptides. We employed isopropanol phosphonic acid (IPPA) as an IMAC ligand for the immobilization of Ti(IV) which could increase the specific adsorption of phosphopeptides. The enrichment and release properties were examined by treatment with pyridoxal 5’-phosphate (PLP) and casein phosphopeptides (CPP). Two phosphorylated compounds above have temperature-stimulated binding to Ti4+. Finally, silica@p (NIPAAm-co-IPPA)-Ti4+ was successfully employed in pretreatment of phosphopeptides in a tryptic digest of a-casein and human serum albumin (HSA). The results indicated a great potential of this new temperature-responsive material in phosphoproteomics study.

Developing Year 2 Students' Theory of Biology with Concepts of the Gene and DNA

ERIC Educational Resources Information Center

Venville, Grady; Donovan, Jenny

2007-01-01

This paper presents a case study of a teaching intervention designed to enrich Year 2 students' theory of biology through the introduction of causal mechanisms of inheritance such as the gene and DNA. The researchers worked collaboratively with the classroom teacher to design the intervention based on the students' prior knowledge of living things…

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles.

PubMed

Digiacomo, L; Cardarelli, F; Pozzi, D; Palchetti, S; Digman, M A; Gratton, E; Capriotti, A L; Mahmoudi, M; Caracciolo, G

2017-11-16

Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively. By conducting confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of the cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano-liquid chromatography tandem mass spectrometry identifies apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.

In silico prediction of protein-protein interactions in human macrophages

PubMed Central

2014-01-01

Background Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level. PMID:24636261

RAMONA: a Web application for gene set analysis on multilevel omics data.

PubMed

Sass, Steffen; Buettner, Florian; Mueller, Nikola S; Theis, Fabian J

2015-01-01

Decreasing costs of modern high-throughput experiments allow for the simultaneous analysis of altered gene activity on various molecular levels. However, these multi-omics approaches lead to a large amount of data, which is hard to interpret for a non-bioinformatician. Here, we present the remotely accessible multilevel ontology analysis (RAMONA). It offers an easy-to-use interface for the simultaneous gene set analysis of combined omics datasets and is an extension of the previously introduced MONA approach. RAMONA is based on a Bayesian enrichment method for the inference of overrepresented biological processes among given gene sets. Overrepresentation is quantified by interpretable term probabilities. It is able to handle data from various molecular levels, while in parallel coping with redundancies arising from gene set overlaps and related multiple testing problems. The comprehensive output of RAMONA is easy to interpret and thus allows for functional insight into the affected biological processes. With RAMONA, we provide an efficient implementation of the Bayesian inference problem such that ontologies consisting of thousands of terms can be processed in the order of seconds. RAMONA is implemented as ASP.NET Web application and publicly available at http://icb.helmholtz-muenchen.de/ramona. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Divergent genome evolution caused by regional variation in DNA gain and loss between human and mouse

PubMed Central

Kortschak, R. Daniel

2018-01-01

The forces driving the accumulation and removal of non-coding DNA and ultimately the evolution of genome size in complex organisms are intimately linked to genome structure and organisation. Our analysis provides a novel method for capturing the regional variation of lineage-specific DNA gain and loss events in their respective genomic contexts. To further understand this connection we used comparative genomics to identify genome-wide individual DNA gain and loss events in the human and mouse genomes. Focusing on the distribution of DNA gains and losses, relationships to important structural features and potential impact on biological processes, we found that in autosomes, DNA gains and losses both followed separate lineage-specific accumulation patterns. However, in both species chromosome X was particularly enriched for DNA gain, consistent with its high L1 retrotransposon content required for X inactivation. We found that DNA loss was associated with gene-rich open chromatin regions and DNA gain events with gene-poor closed chromatin regions. Additionally, we found that DNA loss events tended to be smaller than DNA gain events suggesting that they were able to accumulate in gene-rich open chromatin regions due to their reduced capacity to interrupt gene regulatory architecture. GO term enrichment showed that mouse loss hotspots were strongly enriched for terms related to developmental processes. However, these genes were also located in regions with a high density of conserved elements, suggesting that despite high levels of DNA loss, gene regulatory architecture remained conserved. This is consistent with a model in which DNA gain and loss results in turnover or “churning” in regulatory element dense regions of open chromatin, where interruption of regulatory elements is selected against. PMID:29677183

Concentration dependent transcriptome responses of zebrafish embryos after exposure to cadmium, cobalt and copper.

PubMed

Sonnack, Laura; Klawonn, Thorsten; Kriehuber, Ralf; Hollert, Henner; Schäfers, Christoph; Fenske, Martina

2017-12-01

Environmental metals are known to cause harmful effects to fish of which many molecular mechanisms still require elucidation. Particularly concentration dependence of gene expression effects is unclear. Focusing on this matter, zebrafish embryo toxicity tests were used in combination with transcriptomics. Embryos were exposed to three concentrations of copper (CuSO 4 ), cadmium (CdCl 2 ) and cobalt (CoSO 4 ) from just after fertilization until the end of the 48hpf pre- and 96hpf post-hatch stage. The RNA was then analyzed on Agilent's Zebrafish (V3, 4×44K) arrays. Enrichment for GO terms of biological processes illustrated for cadmium that most affected GO terms were represented in all three concentrations, while for cobalt and copper most GO terms were represented in the lowest test concentration only. This suggested a different response to the non-essential cadmium than cobalt and copper. In cobalt and copper treated embryos, many developmental and cellular processes as well as the Wnt and Notch signaling pathways, were found significantly enriched. Also, different exposure concentrations affected varied functional networks. In contrast, the largest clusters of enriched GO terms for all three concentrations of cadmium included responses to cadmium ion, metal ion, xenobiotic stimulus, stress and chemicals. However, concentration dependence of mRNA levels was evident for several genes in all metal exposures. Some of these genes may be indicative of the mechanisms of action of the individual metals in zebrafish embryos. Real-time quantitative RT-PCR (qRT-PCR) verified the microarray data for mmp9, mt2, cldnb and nkx2.2a. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene co-expression networks shed light into diseases of brain iron accumulation

PubMed Central

Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M.; Botía, Juan A.; Collingwood, Joanna F.; Hardy, John; Milward, Elizabeth A.; Ryten, Mina; Houlden, Henry

2016-01-01

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. PMID:26707700

Application of a post-docking procedure based on MM-PBSA and MM-GBSA on single and multiple protein conformations.

PubMed

Sgobba, Miriam; Caporuscio, Fabiana; Anighoro, Andrew; Portioli, Corinne; Rastelli, Giulio

2012-12-01

In the last decades, molecular docking has emerged as an increasingly useful tool in the modern drug discovery process, but it still needs to overcome many hurdles and limitations such as how to account for protein flexibility and poor scoring function performance. For this reason, it has been recognized that in many cases docking results need to be post-processed to achieve a significant agreement with experimental activities. In this study, we have evaluated the performance of MM-PBSA and MM-GBSA scoring functions, implemented in our post-docking procedure BEAR, in rescoring docking solutions. For the first time, the performance of this post-docking procedure has been evaluated on six different biological targets (namely estrogen receptor, thymidine kinase, factor Xa, adenosine deaminase, aldose reductase, and enoyl ACP reductase) by using i) both a single and a multiple protein conformation approach, and ii) two different software, namely AutoDock and LibDock. The assessment has been based on two of the most important criteria for the evaluation of docking methods, i.e., the ability of known ligands to enrich the top positions of a ranked database with respect to molecular decoys, and the consistency of the docking poses with crystallographic binding modes. We found that, in many cases, MM-PBSA and MM-GBSA are able to yield higher enrichment factors compared to those obtained with the docking scoring functions alone. However, for only a minority of the cases, the enrichment factors obtained by using multiple protein conformations were higher than those obtained by using only one protein conformation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Gene co-expression networks shed light into diseases of brain iron accumulation.

PubMed

Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M; Botía, Juan A; Collingwood, Joanna F; Hardy, John; Milward, Elizabeth A; Ryten, Mina; Houlden, Henry

2016-03-01

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cognitive and behavioral assessment in dogs and pet food market applications.

PubMed

Zicker, Steven C

2005-03-01

A multi-disciplinary program was developed to assess the efficacy of antioxidant inclusion in a canine pet food on cognitive decline in aged beagles. A systematic approach to development of the food was used prior to beginning the cognitive studies. Comprehensive evaluation of antioxidant ingredients included assessments of commodities with naturally occurring antioxidants and synthetic antioxidants not commonly utilized, or at different concentrations than what was commonly utilized, in commercial pet foods. Studies were conducted to insure stability through processing, absorption from the gastrointestinal tract, safety, and tests for potential antioxidant biological benefit by ex vivo tests. Testing of the antioxidant-fortified food in aged beagles slowed the rate of cognitive decline in aged dogs. In addition, environmental enrichment also slowed the rate of cognitive decline. Importantly, the combination of dietary antioxidants and environmental enrichment was synergistic and resulted in the least amount of cognitive decline over the 30-month study period. Finally, a clinical study showed that antioxidant fortified food improved age-related behavioral changes in older pet dogs at in-home situations.

Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?

PubMed

Kaur, Simranjeet; Pociot, Flemming

2015-07-13

Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value < 10e-16), which highlights their importance in T1D. Functional annotation of T1D genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value < 10e-6). We also identified eight T1D genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

PubMed

Cai, Pengfei; Liu, Shuai; Piao, Xianyu; Hou, Nan; Gobert, Geoffrey N; McManus, Donald P; Chen, Qijun

2016-04-01

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Identification of radiation responsive genes and transcriptome profiling via complete RNA sequencing in a stable radioresistant U87 glioblastoma model.

PubMed

Doan, Ninh B; Nguyen, Ha S; Alhajala, Hisham S; Jaber, Basem; Al-Gizawiy, Mona M; Ahn, Eun-Young Erin; Mueller, Wade M; Chitambar, Christopher R; Mirza, Shama P; Schmainda, Kathleen M

2018-05-04

The absence of major progress in the treatment of glioblastoma (GBM) is partly attributable to our poor understanding of both GBM tumor biology and the acquirement of treatment resistance in recurrent GBMs. Recurrent GBMs are characterized by their resistance to radiation. In this study, we used an established stable U87 radioresistant GBM model and total RNA sequencing to shed light on global mRNA expression changes following irradiation. We identified many genes, the expressions of which were altered in our radioresistant GBM model, that have never before been reported to be associated with the development of radioresistant GBM and should be concertedly further investigated to understand their roles in radioresistance. These genes were enriched in various biological processes such as inflammatory response, cell migration, positive regulation of epithelial to mesenchymal transition, angiogenesis, apoptosis, positive regulation of T-cell migration, positive regulation of macrophage chemotaxis, T-cell antigen processing and presentation, and microglial cell activation involved in immune response genes. These findings furnish crucial information for elucidating the molecular mechanisms associated with radioresistance in GBM. Therapeutically, with the global alterations of multiple biological pathways observed in irradiated GBM cells, an effective GBM therapy may require a cocktail carrying multiple agents targeting multiple implicated pathways in order to have a chance at making a substantial impact on improving the overall GBM survival.

A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes.

PubMed

Hansen, Jens; Meretzky, David; Woldesenbet, Simeneh; Stolovitzky, Gustavo; Iyengar, Ravi

2017-12-18

Whole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the Molecular Biology of the Cell Ontology based on standard cell biology and biochemistry textbooks and review articles. Currently, our ontology contains 5,384 genes, 753 SCPs and 19,180 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how SCPs together can give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed SCP networks for predictive modeling of emergent whole cell functions.

Proteomic analysis of effects by x-rays and heavy ion in HeLa cells.

PubMed

Bing, Zhitong; Yang, Guanghui; Zhang, Yanan; Wang, Fengling; Ye, Caiyong; Sun, Jintu; Zhou, Guangming; Yang, Lei

2014-06-01

Carbon ion therapy may be better against cancer than the effects of a photon beam. To investigate a biological advantage of carbon ion beam over X-rays, the radioresistant cell line HeLa cells were used. Radiation-induced changes in the biological processes were investigated post-irradiation at 1 h by a clinically relevant radiation dose (2 Gy X-ray and 2 Gy carbon beam). The differential expression proteins were collected for analysing biological effects. The radioresistant cell line Hela cells were used. In our study, the stable isotope labelling with amino acids (SILAC) method coupled with 2D-LC-LTQ Orbitrap mass spectrometry was applied to identity and quantify the differentially expressed proteins after irradiation. The Western blotting experiment was used to validate the data. A total of 123 and 155 significantly changed proteins were evaluated with treatment of 2 Gy carbon and X-rays after radiation 1 h, respectively. These deregulated proteins were found to be mainly involved in several kinds of metabolism processes through Gene Ontology (GO) enrichment analysis. The two groups perform different response to different types of irradiation. The radioresistance of the cancer cells treated with 2 Gy X-rays irradiation may be largely due to glycolysis enhancement, while the greater killing effect of 2 Gy carbon may be due to unchanged glycolysis and decreased amino acid metabolism.

Dengue-2 structural proteins associate with human proteins to produce a coagulation and innate immune response biased interactome.

PubMed

Folly, Brenda B; Weffort-Santos, Almeriane M; Fathman, C G; Soares, Luis R B

2011-01-31

Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem. A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology. Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis. Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti-viral response processes, and predicts that the interaction of dengue proteins with a proposed human protein interaction network produces a modified biological outcome that may be behind the hallmark pathologies of dengue infection.

Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

PubMed Central

Regan, Kelly; Wang, Kanix; Doughty, Emily; Li, Haiquan; Li, Jianrong; Lee, Younghee; Kann, Maricel G

2012-01-01

Objective Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. Materials and methods An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. Results Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). Discussion The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). Conclusion These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for identifying novel targets, for repositioning drugs, and for personal therapeutics. PMID:22319180

Quantitative proteomics reveals a dynamic association of proteins to detergent-resistant membranes upon elicitor signaling in tobacco.

PubMed

Stanislas, Thomas; Bouyssie, David; Rossignol, Michel; Vesa, Simona; Fromentin, Jérôme; Morel, Johanne; Pichereaux, Carole; Monsarrat, Bernard; Simon-Plas, Françoise

2009-09-01

A large body of evidence from the past decade supports the existence, in membrane from animal and yeast cells, of functional microdomains playing important roles in protein sorting, signal transduction, or infection by pathogens. In plants, as previously observed for animal microdomains, detergent-resistant fractions, enriched in sphingolipids and sterols, were isolated from plasma membrane. A characterization of their proteic content revealed their enrichment in proteins involved in signaling and response to biotic and abiotic stress and cell trafficking suggesting that these domains were likely to be involved in such physiological processes. In the present study, we used (14)N/(15)N metabolic labeling to compare, using a global quantitative proteomics approach, the content of tobacco detergent-resistant membranes extracted from cells treated or not with cryptogein, an elicitor of defense reaction. To analyze the data, we developed a software allowing an automatic quantification of the proteins identified. The results obtained indicate that, although the association to detergent-resistant membranes of most proteins remained unchanged upon cryptogein treatment, five proteins had their relative abundance modified. Four proteins related to cell trafficking (four dynamins) were less abundant in the detergent-resistant membrane fraction after cryptogein treatment, whereas one signaling protein (a 14-3-3 protein) was enriched. This analysis indicates that plant microdomains could, like their animal counterpart, play a role in the early signaling process underlying the setup of defense reaction. Furthermore proteins identified as differentially associated to tobacco detergent-resistant membranes after cryptogein challenge are involved in signaling and vesicular trafficking as already observed in similar studies performed in animal cells upon biological stimuli. This suggests that the ways by which the dynamic association of proteins to microdomains could participate in the regulation of the signaling process may be conserved between plant and animals.

Quantitative Proteomics Reveals a Dynamic Association of Proteins to Detergent-resistant Membranes upon Elicitor Signaling in Tobacco*

PubMed Central

Stanislas, Thomas; Bouyssie, David; Rossignol, Michel; Vesa, Simona; Fromentin, Jérôme; Morel, Johanne; Pichereaux, Carole; Monsarrat, Bernard; Simon-Plas, Françoise

2009-01-01

A large body of evidence from the past decade supports the existence, in membrane from animal and yeast cells, of functional microdomains playing important roles in protein sorting, signal transduction, or infection by pathogens. In plants, as previously observed for animal microdomains, detergent-resistant fractions, enriched in sphingolipids and sterols, were isolated from plasma membrane. A characterization of their proteic content revealed their enrichment in proteins involved in signaling and response to biotic and abiotic stress and cell trafficking suggesting that these domains were likely to be involved in such physiological processes. In the present study, we used 14N/15N metabolic labeling to compare, using a global quantitative proteomics approach, the content of tobacco detergent-resistant membranes extracted from cells treated or not with cryptogein, an elicitor of defense reaction. To analyze the data, we developed a software allowing an automatic quantification of the proteins identified. The results obtained indicate that, although the association to detergent-resistant membranes of most proteins remained unchanged upon cryptogein treatment, five proteins had their relative abundance modified. Four proteins related to cell trafficking (four dynamins) were less abundant in the detergent-resistant membrane fraction after cryptogein treatment, whereas one signaling protein (a 14-3-3 protein) was enriched. This analysis indicates that plant microdomains could, like their animal counterpart, play a role in the early signaling process underlying the setup of defense reaction. Furthermore proteins identified as differentially associated to tobacco detergent-resistant membranes after cryptogein challenge are involved in signaling and vesicular trafficking as already observed in similar studies performed in animal cells upon biological stimuli. This suggests that the ways by which the dynamic association of proteins to microdomains could participate in the regulation of the signaling process may be conserved between plant and animals. PMID:19525550

Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways.

PubMed

Karbalaei, Reza; Allahyari, Marzieh; Rezaei-Tavirani, Mostafa; Asadzadeh-Aghdaei, Hamid; Zali, Mohammad Reza

2018-01-01

Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on. Therefore, systems biology approach can help to discover their relationship. DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. An R package used to define best centrality method. Finally, based on degree and Betweenness, hubs and bottleneck nodes were defined. Common genes between NAFLD and Alzheimer`s disease were 190 genes that used construct a network with STRING database. The resulting network contained 182 nodes and 2591 edges and comprises from four clusters. Enrichment of these clusters separately lead to carbohydrate metabolism, long chain fatty acid and regulation of JAK-STAT and IL-17 signaling pathways, respectively. Also seven genes selected as hub-bottleneck include: IL6, AKT1, TP53, TNF, JUN, VEGFA and PPARG. Enrichment of these proteins and their first neighbors in network by OMIM database lead to diabetes and obesity as ancestors of NAFLD and AD. Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

Gene expression profiles in whole blood and associations with metabolic dysregulation in obesity.

PubMed

Cox, Amanda J; Zhang, Ping; Evans, Tiffany J; Scott, Rodney J; Cripps, Allan W; West, Nicholas P

Gene expression data provides one tool to gain further insight into the complex biological interactions linking obesity and metabolic disease. This study examined associations between blood gene expression profiles and metabolic disease in obesity. Whole blood gene expression profiles, performed using the Illumina HT-12v4 Human Expression Beadchip, were compared between (i) individuals with obesity (O) or lean (L) individuals (n=21 each), (ii) individuals with (M) or without (H) Metabolic Syndrome (n=11 each) matched on age and gender. Enrichment of differentially expressed genes (DEG) into biological pathways was assessed using Ingenuity Pathway Analysis. Association between sets of genes from biological pathways considered functionally relevant and Metabolic Syndrome were further assessed using an area under the curve (AUC) and cross-validated classification rate (CR). For OvL, only 50 genes were significantly differentially expressed based on the selected differential expression threshold (1.2-fold, p<0.05). For MvH, 582 genes were significantly differentially expressed (1.2-fold, p<0.05) and pathway analysis revealed enrichment of DEG into a diverse set of pathways including immune/inflammatory control, insulin signalling and mitochondrial function pathways. Gene sets from the mTOR signalling pathways demonstrated the strongest association with Metabolic Syndrome (p=8.1×10 -8 ; AUC: 0.909, CR: 72.7%). These results support the use of expression profiling in whole blood in the absence of more specific tissue types for investigations of metabolic disease. Using a pathway analysis approach it was possible to identify an enrichment of DEG into biological pathways that could be targeted for in vitro follow-up. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Enhancing Reuse of Data and Biological Material in Medical Research: From FAIR to FAIR-Health

PubMed Central

Kohlmayer, Florian; Prasser, Fabian; Mayrhofer, Michaela Th.; Schlünder, Irene; Martin, Gillian M.; Casati, Sara; Koumakis, Lefteris; Wutte, Andrea; Kozera, Łukasz; Strapagiel, Dominik; Anton, Gabriele; Zanetti, Gianluigi; Sezerman, Osman Ugur; Mendy, Maimuna; Valík, Dalibor; Lavitrano, Marialuisa; Dagher, Georges; Zatloukal, Kurt; van Ommen, GertJan B.; Litton, Jan-Eric

2018-01-01

The known challenge of underutilization of data and biological material from biorepositories as potential resources for medical research has been the focus of discussion for over a decade. Recently developed guidelines for improved data availability and reusability—entitled FAIR Principles (Findability, Accessibility, Interoperability, and Reusability)—are likely to address only parts of the problem. In this article, we argue that biological material and data should be viewed as a unified resource. This approach would facilitate access to complete provenance information, which is a prerequisite for reproducibility and meaningful integration of the data. A unified view also allows for optimization of long-term storage strategies, as demonstrated in the case of biobanks. We propose an extension of the FAIR Principles to include the following additional components: (1) quality aspects related to research reproducibility and meaningful reuse of the data, (2) incentives to stimulate effective enrichment of data sets and biological material collections and its reuse on all levels, and (3) privacy-respecting approaches for working with the human material and data. These FAIR-Health principles should then be applied to both the biological material and data. We also propose the development of common guidelines for cloud architectures, due to the unprecedented growth of volume and breadth of medical data generation, as well as the associated need to process the data efficiently. PMID:29359962

Enhancing Reuse of Data and Biological Material in Medical Research: From FAIR to FAIR-Health.

PubMed

Holub, Petr; Kohlmayer, Florian; Prasser, Fabian; Mayrhofer, Michaela Th; Schlünder, Irene; Martin, Gillian M; Casati, Sara; Koumakis, Lefteris; Wutte, Andrea; Kozera, Łukasz; Strapagiel, Dominik; Anton, Gabriele; Zanetti, Gianluigi; Sezerman, Osman Ugur; Mendy, Maimuna; Valík, Dalibor; Lavitrano, Marialuisa; Dagher, Georges; Zatloukal, Kurt; van Ommen, GertJan B; Litton, Jan-Eric

2018-04-01

The known challenge of underutilization of data and biological material from biorepositories as potential resources for medical research has been the focus of discussion for over a decade. Recently developed guidelines for improved data availability and reusability-entitled FAIR Principles (Findability, Accessibility, Interoperability, and Reusability)-are likely to address only parts of the problem. In this article, we argue that biological material and data should be viewed as a unified resource. This approach would facilitate access to complete provenance information, which is a prerequisite for reproducibility and meaningful integration of the data. A unified view also allows for optimization of long-term storage strategies, as demonstrated in the case of biobanks. We propose an extension of the FAIR Principles to include the following additional components: (1) quality aspects related to research reproducibility and meaningful reuse of the data, (2) incentives to stimulate effective enrichment of data sets and biological material collections and its reuse on all levels, and (3) privacy-respecting approaches for working with the human material and data. These FAIR-Health principles should then be applied to both the biological material and data. We also propose the development of common guidelines for cloud architectures, due to the unprecedented growth of volume and breadth of medical data generation, as well as the associated need to process the data efficiently.

The Dynamic Duo–Inflammatory M1 macrophages and Th17 cells in Rheumatic Diseases

PubMed Central

Li, Jun; Hsu, Hui-Chen; Mountz, John D.

2014-01-01

The synovial tissue of Rheumatoid Arthritis (RA) patients is enriched with macrophages and T lymphocytes which are two central players in the pathogenesis of RA. Interaction between myeloid cells and T cells are essential for the initiation and progression of the inflammatory processes in the synovium. With the rapid evolution of our understanding of how these two cell types are involved in the regulation of immune responses, RA is emerging as an ideal disease model for investigating the cell-cell interactions and consequently introducing novel biologic agents that are designed to disrupt these processes. This review will discuss the bidirectional interaction between the IL-23+ inflammatory macrophages and IL-17+ GM-CSF+ CD4 T cells in rheumatic diseases as well as potential antirheumatic strategies via apoptosis induction in this context. PMID:25309946

31 CFR 540.316 - Uranium enrichment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Uranium enrichment. 540.316 Section 540.316 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process of...

The LncRNA Connectivity Map: Using LncRNA Signatures to Connect Small Molecules, LncRNAs, and Diseases.

PubMed

Yang, Haixiu; Shang, Desi; Xu, Yanjun; Zhang, Chunlong; Feng, Li; Sun, Zeguo; Shi, Xinrui; Zhang, Yunpeng; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

2017-07-27

Well characterized the connections among diseases, long non-coding RNAs (lncRNAs) and drugs are important for elucidating the key roles of lncRNAs in biological mechanisms in various biological states. In this study, we constructed a database called LNCmap (LncRNA Connectivity Map), available at http://www.bio-bigdata.com/LNCmap/ , to establish the correlations among diseases, physiological processes, and the action of small molecule therapeutics by attempting to describe all biological states in terms of lncRNA signatures. By reannotating the microarray data from the Connectivity Map database, the LNCmap obtained 237 lncRNA signatures of 5916 instances corresponding to 1262 small molecular drugs. We provided a user-friendly interface for the convenient browsing, retrieval and download of the database, including detailed information and the associations of drugs and corresponding affected lncRNAs. Additionally, we developed two enrichment analysis methods for users to identify candidate drugs for a particular disease by inputting the corresponding lncRNA expression profiles or an associated lncRNA list and then comparing them to the lncRNA signatures in our database. Overall, LNCmap could significantly improve our understanding of the biological roles of lncRNAs and provide a unique resource to reveal the connections among drugs, lncRNAs and diseases.

t4 report1

PubMed Central

Zhu, Hao; Bouhifd, Mounir; Kleinstreuer, Nicole; Kroese, E. Dinant; Liu, Zhichao; Luechtefeld, Thomas; Pamies, David; Shen, Jie; Strauss, Volker; Wu, Shengde; Hartung, Thomas

2016-01-01

Summary Read-across, i.e. filling toxicological data gaps by relating to similar chemicals, for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, however, biological similarity based on biological data adds extra strength to this process. In the context of developing Good Read-Across Practice guidance, a number of case studies were evaluated to demonstrate the use of biological data to enrich read-across. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of e.g. genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances become increasingly available enabling big data approaches in read-across studies. Several case studies using various big data sources are described in this paper. An example is given for the US EPA’s ToxCast dataset allowing read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example for REACH registration data enhancing read-across for acute toxicity studies is given. A different approach is taken using omics data to establish biological similarity: Examples are given for stem cell models in vitro and short-term repeated dose studies in rats in vivo to support read-across and category formation. These preliminary biological data-driven read-across studies highlight the road to the new generation of read-across approaches that can be applied in chemical safety assessment. PMID:26863516

Distribution and Catabolic Diversity of 3-Chlorobenzoic Acid Degrading Bacteria Isolated from Geographically-Separated Pristine Soils

DTIC Science & Technology

1994-08-01

influence on the structure of 3-CBA degrading populations. This suggests that if substrate exposure is important, secondary metabolites produced during the...enrichments were treated with 50 gIg 3-CBAgodry-soil- 1 and secondary enrichments were performed with 50 p.g 3-CBA ml-1 d•tfined medium. Isolates were...not attempt to determine metabolites or if transformations were biologically mediated. As a result, it was not clear whether disappearance of a

Investigation of candidate genes for osteoarthritis based on gene expression profiles.

PubMed

Dong, Shuanghai; Xia, Tian; Wang, Lei; Zhao, Qinghua; Tian, Jiwei

2016-12-01

To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules. In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs were involved in inflammatory response, while down-regulated DEGs were involved in cell cycle. PPI network with 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle. The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for gene therapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle and cytokine-cytokine receptor interaction pathway. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Optimisation of dynamic nuclear polarisation of [1-13C] pyruvate by addition of gadolinium-based contrast agents

NASA Astrophysics Data System (ADS)

Friesen-Waldner, Lanette; Chen, Albert; Mander, Will; Scholl, Timothy J.; McKenzie, Charles A.

2012-10-01

Dynamic nuclear polarisation (DNP) of carbon-13 (13C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the 13C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T1) of the 13C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-13C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T1 of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T1 (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T1 in experiments with hyperpolarised 13C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised 13C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T1 is especially problematic.

Circular RNA expression profiles in placental villi from women with gestational diabetes mellitus.

PubMed

Yan, Linping; Feng, Jie; Cheng, Feng; Cui, Xianwei; Gao, Lingjuan; Chen, Yajun; Wang, Fei; Zhong, Tianying; Li, Yun; Liu, Lan

2018-04-15

Circular RNAs (circRNAs) have recently been shown to exert their effects on multiple pathological processes by acting as microRNA (miRNA) sponges. However, the roles of circRNAs in gestational diabetes mellitus (GDM) are largely unknown. This study aimed to identify the circRNAs involved in GDM and predict their potential biological functions. We first performed next-generation sequencing (NGS) to generate unbiased placental villi circRNA expression profiles of GDM and normal controls. In total, 48,270 circRNAs from the placental villi of the two groups were sequenced. Of these, 227 circRNAs were significantly up-regulated and 255 circRNAs were significantly down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that glycometabolism and lipometabolism processes, which are important in GDM development, were significantly enriched. Further analysis showed that most of the circRNAs harbored miRNA binding sites, and some were associated with GDM. These results showed that circRNAs are aberrantly expressed in the placental villi of GDM patients and play potential roles in the development of GDM. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative phosphoproteomic analysis of caprine muscle with high and low meat quality.

PubMed

Liu, Manshun; Wei, Yanchao; Li, Xin; Quek, Siew Young; Zhao, Jing; Zhong, Huazhen; Zhang, Dequan; Liu, Yongfeng

2018-07-01

During the conversion of muscle to meat, protein phosphorylation can regulate various biological processes that have important effects on meat quality. To investigate the phosphorylation pattern of protein on rigor mortis, goat longissimus thoracis and external intercostals were classified into two groups (high quality and low quality), and meat quality was evaluated according to meat quality attributes (Warner-Bratzler shear force, Color, pH and drip loss). A quantitative mass spectrometry-based phosphoproteomic study was conducted to analyze the caprine muscle at 12h postmortem applying the TiO 2 -SIMAC-HILIC (TiSH) phosphopeptide enrichment strategy. A total of 2125 phosphopeptides were identified from 750 phosphoproteins. Among them, 96 proteins had differed in phosphorylation levels. The majority of these proteins are involved in glucose metabolism and muscle contraction. The differential phosphorylation level of proteins (PFK, MYL2 and HSP27) in two groups may be the crucial factors of regulating muscle rigor mortis. This study provides a comprehensive view for the phosphorylation status of caprine muscle at rigor mortis, it also gives a better understanding of the regulation of protein phosphorylation on various biological processes that affect the final meat quality attributes. Copyright © 2018. Published by Elsevier Ltd.

Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.

PubMed

Fan, Yanxia; Xiao, Shuping

2018-06-23

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

A Range Finding Protocol to Support Design for Transcriptomics Experimentation: Examples of In-Vitro and In-Vivo Murine UV Exposure

PubMed Central

van Oostrom, Conny T.; Jonker, Martijs J.; de Jong, Mark; Dekker, Rob J.; Rauwerda, Han; Ensink, Wim A.; de Vries, Annemieke; Breit, Timo M.

2014-01-01

In transcriptomics research, design for experimentation by carefully considering biological, technological, practical and statistical aspects is very important, because the experimental design space is essentially limitless. Usually, the ranges of variable biological parameters of the design space are based on common practices and in turn on phenotypic endpoints. However, specific sub-cellular processes might only be partially reflected by phenotypic endpoints or outside the associated parameter range. Here, we provide a generic protocol for range finding in design for transcriptomics experimentation based on small-scale gene-expression experiments to help in the search for the right location in the design space by analyzing the activity of already known genes of relevant molecular mechanisms. Two examples illustrate the applicability: in-vitro UV-C exposure of mouse embryonic fibroblasts and in-vivo UV-B exposure of mouse skin. Our pragmatic approach is based on: framing a specific biological question and associated gene-set, performing a wide-ranged experiment without replication, eliminating potentially non-relevant genes, and determining the experimental ‘sweet spot’ by gene-set enrichment plus dose-response correlation analysis. Examination of many cellular processes that are related to UV response, such as DNA repair and cell-cycle arrest, revealed that basically each cellular (sub-) process is active at its own specific spot(s) in the experimental design space. Hence, the use of range finding, based on an affordable protocol like this, enables researchers to conveniently identify the ‘sweet spot’ for their cellular process of interest in an experimental design space and might have far-reaching implications for experimental standardization. PMID:24823911

Geochemical and geo-statistical assessment of selected heavy metals in the surface sediments of the Gorgan Bay, Iran.

PubMed

Bastami, Kazem Darvish; Bagheri, Hossein; Haghparast, Sarah; Soltani, Farzaneh; Hamzehpoor, Ali; Bastami, Mousa Darvish

2012-12-01

We investigated heavy metal concentrations of zinc (Zn), copper (Cu), chromium (Cr), and lead (Pb), their spatial distribution and enrichment factor index in surface sediments of the Gorgan Bay. Sediment Quality Guidelines were also applied to assess adverse biological effects of these metals. Heavy metals were determined by inductively coupled plasma-mass spectroscopy (ICP-MS). The results indicated mean concentrations (ppm) of heavy metals were (mean±S.D.) Pb: 11.5±4.88, Cu: 18±8.83, Zn: 42±22.15 and Cr: 32±15.19. Based on Enrichment index, the Gorgan Bay is a low-enriched to non-enriched bay. Heavy metal contents were lower than the standard limits of PEL, ERL, and ERM that reveal no threatening influence of the metals in the Bay. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements

PubMed Central

Hayes, James E.; Trynka, Gosia; Vijai, Joseph; Offit, Kenneth; Raychaudhuri, Soumya; Klein, Robert J.

2015-01-01

Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkin’s lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well. PMID:26422229

Prediction of skin anti-aging clinical benefits of an association of ingredients from marine and maritime origins: Ex vivo evaluation using a label-free quantitative proteomic and customized data processing approach.

PubMed

Hameury, Sebastien; Borderie, Laurent; Monneuse, Jean-Marc; Skorski, Gilbert; Pradines, Dominique

2018-05-23

The application of ingredients from marine and maritime origins is increasingly common in skin care products, driven by consumer expectations for natural ingredients. However, these ingredients are typically studied for a few isolated in vitro activities. The purpose of this study was to carry out a comprehensive evaluation of the activity on the skin of an association of ingredients from marine and maritime origins using label-free quantitative proteomic analysis, in order to predict the clinical benefits if used in a skin care product. An aqueous gel containing 6.1% of ingredients from marine and maritime origins (amino acid-enriched giant kelp extract, trace element-enriched seawater, dedifferentiated sea fennel cells) was topically applied on human skin explants. The skin explants' proteome was analyzed in a label-free manner by high-performance liquid nano-chromatography coupled with tandem mass spectrometry. A specific data processing pipeline (CORAVALID) providing an objective and comprehensive interpretation of the statistically relevant biological activities processed the results. Compared to untreated skin explants, 64 proteins were significantly regulated by the gel treatment (q-value ≤ 0.05). Computer data processing revealed an activity of the ingredients on the epidermis and the dermis. These significantly regulated proteins are involved in gene expression, cell survival and metabolism, inflammatory processes, dermal extracellular matrix synthesis, melanogenesis and keratinocyte proliferation, migration, and differentiation. These results suggest that the tested ingredients could help to preserve a healthy epidermis and dermis, and possibly to prevent the visible signs of skin aging. © 2018 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update.

PubMed

Kuleshov, Maxim V; Jones, Matthew R; Rouillard, Andrew D; Fernandez, Nicolas F; Duan, Qiaonan; Wang, Zichen; Koplev, Simon; Jenkins, Sherry L; Jagodnik, Kathleen M; Lachmann, Alexander; McDermott, Michael G; Monteiro, Caroline D; Gundersen, Gregory W; Ma'ayan, Avi

2016-07-08

Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Enrichment with Wood Blocks Does Not Affect Toxicity Assessment in an Exploratory Toxicology Model Using Sprague–Dawley Rats

PubMed Central

Ditewig, Amy C; Bratcher, Natalie A; Davila, Donna R; Dayton, Brian D; Ebert, Paige; Lesuisse, Philippe; Liguori, Michael J; Wetter, Jill M; Yang, Hyuna; Buck, Wayne R

2014-01-01

Environmental enrichment in rodents may improve animal well-being but can affect neurologic development, immune system function, and aging. We tested the hypothesis that wood block enrichment affects the interpretation of traditional and transcriptomic endpoints in an exploratory toxicology testing model using a well-characterized reference compound, cyclophosphamide. ANOVA was performed to distinguish effects of wood block enrichment separate from effects of 40 mg/kg cyclophosphamide treatment. Biologically relevant and statistically significant effects of wood block enrichment occurred only for body weight gain. ANOVA demonstrated the expected effects of cyclophosphamide on food consumption, spleen weight, and hematology. According to transcriptomic endpoints, cyclophosphamide induced fewer changes in gene expression in liver than in spleen. Splenic transcriptomic pathways affected by cyclophosphamide included: iron hemostasis; vascular tissue angiotensin system; hepatic stellate cell activation and fibrosis; complement activation; TGFβ-induced hypertrophy and fibrosis; monocytes, macrophages, and atherosclerosis; and platelet activation. Changes in these pathways due to cyclophosphamide treatment were consistent with bone marrow toxicity regardless of enrichment. In a second study, neither enrichment nor type of cage flooring altered body weight or food consumption over a 28-d period after the first week. In conclusion, wood block enrichment did not interfere with a typical exploratory toxicology study; the effects of ingested wood on drug level kinetics may require further consideration. PMID:24827566

Improved Discovery of Molecular Interactions in Genome-Scale Data with Adaptive Model-Based Normalization

PubMed Central

Brown, Patrick O.

2013-01-01

Background High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold – yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data. Methods In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data. Results and Conclusions The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied. PMID:23349766

Applying behavior-analytic methodology to the science and practice of environmental enrichment in zoos and aquariums.

PubMed

Alligood, Christina A; Dorey, Nicole R; Mehrkam, Lindsay R; Leighty, Katherine A

2017-05-01

Environmental enrichment in zoos and aquariums is often evaluated at two overlapping levels: published research and day-to-day institutional record keeping. Several authors have discussed ongoing challenges with small sample sizes in between-groups zoological research and have cautioned against the inappropriate use of inferential statistics (Shepherdson, , International Zoo Yearbook, 38, 118-124; Shepherdson, Lewis, Carlstead, Bauman, & Perrin, Applied Animal Behaviour Science, 147, 298-277; Swaisgood, , Applied Animal Behaviour Science, 102, 139-162; Swaisgood & Shepherdson, , Zoo Biology, 24, 499-518). Multi-institutional studies are the typically-prescribed solution, but these are expensive and difficult to carry out. Kuhar ( Zoo Biology, 25, 339-352) provided a reminder that inferential statistics are only necessary when one wishes to draw general conclusions at the population level. Because welfare is assessed at the level of the individual animal, we argue that evaluations of enrichment efficacy are often instances in which inferential statistics may be neither necessary nor appropriate. In recent years, there have been calls for the application of behavior-analytic techniques to zoo animal behavior management, including environmental enrichment (e.g., Bloomsmith, Marr, & Maple, , Applied Animal Behaviour Science, 102, 205-222; Tarou & Bashaw, , Applied Animal Behaviour Science, 102, 189-204). Single-subject (also called single-case, or small-n) designs provide a means of designing evaluations of enrichment efficacy based on an individual's behavior. We discuss how these designs might apply to research and practice goals at zoos and aquariums, contrast them with standard practices in the field, and give examples of how each could be successfully applied in a zoo or aquarium setting. © 2017 Wiley Periodicals, Inc.

Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence

PubMed Central

Blevins, Tana; Aliev, Fazil; Adkins, Amy; Hack, Laura; Bigdeli, Tim; D. van der Vaart, Andrew; Web, Bradley Todd; Bacanu, Silviu-Alin; Kalsi, Gursharan; Kendler, Kenneth S.; Miles, Michael F.; Dick, Danielle; Riley, Brien P.; Dumur, Catherine; Vladimirov, Vladimir I.

2015-01-01

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PMID:26381263

Volcanology: Petit spots go big

NASA Astrophysics Data System (ADS)

Snow, Jonathan E.

2016-12-01

Mantle enrichment processes were thought to be limited to parts of oceanic plates influenced by plumes and to continental interiors. Analyses of mantle fragments of the Pacific Plate suggest that such enrichment processes may operate everywhere.

Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding

PubMed Central

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID:22096593

Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding.

PubMed

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes.

Competition between Methanogens and Acetogens in Biocathodes: A Comparison between Potentiostatic and Galvanostatic Control

PubMed Central

Molenaar, Sam D.; Saha, Pradip; Mol, Annemerel R.; Sleutels, Tom H. J. A.; ter Heijne, Annemiek; Buisman, Cees J. N.

2017-01-01

Microbial electrosynthesis is a useful form of technology for the renewable production of organic commodities from biologically catalyzed reduction of CO2. However, for the technology to become applicable, process selectivity, stability and efficiency need strong improvement. Here we report on the effect of different electrochemical control modes (potentiostatic/galvanostatic) on both the start-up characteristics and steady-state performance of biocathodes using a non-enriched mixed-culture inoculum. Based on our results, it seems that kinetic differences exist between the two dominant functional microbial groups (i.e., homoacetogens and methanogens) and that by applying different current densities, these differences may be exploited to steer product selectivity and reactor performance. PMID:28106846

Competition between Methanogens and Acetogens in Biocathodes: A Comparison between Potentiostatic and Galvanostatic Control.

PubMed

Molenaar, Sam D; Saha, Pradip; Mol, Annemerel R; Sleutels, Tom H J A; Ter Heijne, Annemiek; Buisman, Cees J N

2017-01-19

Microbial electrosynthesis is a useful form of technology for the renewable production of organic commodities from biologically catalyzed reduction of CO₂. However, for the technology to become applicable, process selectivity, stability and efficiency need strong improvement. Here we report on the effect of different electrochemical control modes (potentiostatic/galvanostatic) on both the start-up characteristics and steady-state performance of biocathodes using a non-enriched mixed-culture inoculum. Based on our results, it seems that kinetic differences exist between the two dominant functional microbial groups (i.e., homoacetogens and methanogens) and that by applying different current densities, these differences may be exploited to steer product selectivity and reactor performance.

New insights on glucosylated lipids: metabolism and functions.

PubMed

Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

2013-09-01

Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

PubMed Central

Yi, Ming; Horton, Jay D; Cohen, Jonathan C; Hobbs, Helen H; Stephens, Robert M

2006-01-01

Background Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. Result WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. Conclusion This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at . PMID:16423281

Broad-Enrich: functional interpretation of large sets of broad genomic regions.

PubMed

Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A

2014-09-01

Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. http://broad-enrich.med.umich.edu for Web version and R package. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Nitrogen enrichment regulates calcium sources in forests

USGS Publications Warehouse

Hynicka, Justin D.; Pett-Ridge, Julie C.; Perakis, Steven

2016-01-01

Nitrogen (N) is a key nutrient that shapes cycles of other essential elements in forests, including calcium (Ca). When N availability exceeds ecosystem demands, excess N can stimulate Ca leaching and deplete Ca from soils. Over the long term, these processes may alter the proportion of available Ca that is derived from atmospheric deposition vs. bedrock weathering, which has fundamental consequences for ecosystem properties and nutrient supply. We evaluated how landscape variation in soil N, reflecting long-term legacies of biological N fixation, influenced plant and soil Ca availability and ecosystem Ca sources across 22 temperate forests in Oregon. We also examined interactions between soil N and bedrock Ca using soil N gradients on contrasting basaltic vs. sedimentary bedrock that differed 17-fold in underlying Ca content. We found that low-N forests on Ca-rich basaltic bedrock relied strongly on Ca from weathering, but that soil N enrichment depleted readily weatherable mineral Ca and shifted forest reliance toward atmospheric Ca. Forests on Ca-poor sedimentary bedrock relied more consistently on atmospheric Ca across all levels of soil N enrichment. The broad importance of atmospheric Ca was unexpected given active regional uplift and erosion that are thought to rejuvenate weathering supply of soil minerals. Despite different Ca sources to forests on basaltic vs. sedimentary bedrock, we observed consistent declines in plant and soil Ca availability with increasing N, regardless of the Ca content of underlying bedrock. Thus, traditional measures of Ca availability in foliage and soil exchangeable pools may poorly reflect long-term Ca sources that sustain soil fertility. We conclude that long-term soil N enrichment can deplete available Ca and cause forests to rely increasingly on Ca from atmospheric deposition, which may limit ecosystem Ca supply in an increasingly N-rich world.

Examination of Glycan Profiles from IgG-Depleted Human Immunoglobulins Facilitated by Microscale Affinity Chromatography

PubMed Central

Svoboda, Martin; Mann, Benjamin F.; Goetz, John A.; Novotny, Milos V.

2012-01-01

Among the most important proteins involved in the disease and healing processes are the immunoglobulins (Igs). Although many of the Igs have been studied through proteomics, aside from IgG, immunoglobulin carbohydrates have not been extensively characterized in different states of health. It seems valuable to develop techniques that permit us to understand changes in the structures and abundances of Ig glycans in the context of disease onset and progression. We have devised a strategy for characterization of the glycans for the Ig classes other than IgG (i.e. A, D, E, and M) that contain kappa light chains, while using only a few microliters of biological material. First, we designed a microcolumn containing the recombinant Protein L that was immobilized on macroporous silica particles. A similarly designed Protein G microcolumn was utilized to first perform an on-line depletion of the IgG from the sample, human blood serum, and thereby facilitate enrichment of the other Igs. While only 3 μL of serum were used in these analyses, we were able to recover a significantly-enriched fraction of non-IgG immunoglobulins. The enrichment properties of the Protein L column were characterized using a highly sensitive label-free quantitative proteomics LC-MS/MS approach, and the glycomic profiles of enriched immunoglobulins were measured by MALDI-TOF-MS. As a proof-of-principle, a comparative study was conducted using blood serum from a small group of lung cancer patients and a group of age-matched cancer-free individuals to demonstrate that the method is suitable for investigation of glycosylation changes in disease. The results were in agreement with a glycomic investigation of whole blood serum from a much larger lung cancer cohort. PMID:22360417

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

PubMed

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

PubMed Central

Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

Major Transcriptome Reprogramming Underlies Floral Mimicry Induced by the Rust Fungus Puccinia monoica in Boechera stricta

PubMed Central

Haugen, Riston H.; Saunders, Diane G. O.; Leonelli, Lauriebeth; MacLean, Dan; Hogenhout, Saskia A.; Kamoun, Sophien

2013-01-01

Pucciniamonoica is a spectacular plant parasitic rust fungus that triggers the formation of flower-like structures (pseudoflowers) in its Brassicaceae host plant Boechera stricta . Pseudoflowers mimic in shape, color, nectar and scent co-occurring and unrelated flowers such as buttercups. They act to attract insects thereby aiding spore dispersal and sexual reproduction of the rust fungus. Although much ecological research has been performed on P . monoica -induced pseudoflowers, this system has yet to be investigated at the molecular or genomic level. To date, the molecular alterations underlying the development of pseudoflowers and the genes involved have not been described. To address this, we performed gene expression profiling to reveal 256 plant biological processes that are significantly altered in pseudoflowers. Among these biological processes, plant genes involved in cell fate specification, regulation of transcription, reproduction, floral organ development, anthocyanin (major floral pigments) and terpenoid biosynthesis (major floral volatile compounds) were down-regulated in pseudoflowers. In contrast, plant genes involved in shoot, cotyledon and leaf development, carbohydrate transport, wax biosynthesis, cutin transport and L-phenylalanine metabolism (pathway that results in phenylethanol and phenylacetaldehyde volatile production) were up-regulated. These findings point to an extensive reprogramming of host genes by the rust pathogen to induce floral mimicry. We also highlight 31 differentially regulated plant genes that are enriched in the biological processes mentioned above, and are potentially involved in the formation of pseudoflowers. This work illustrates the complex perturbations induced by rust pathogens in their host plants, and provides a starting point for understanding the molecular mechanisms of pathogen-induced floral mimicry. PMID:24069397

Major transcriptome reprogramming underlies floral mimicry induced by the rust fungus Puccinia monoica in Boechera stricta.

PubMed

Cano, Liliana M; Raffaele, Sylvain; Haugen, Riston H; Saunders, Diane G O; Leonelli, Lauriebeth; MacLean, Dan; Hogenhout, Saskia A; Kamoun, Sophien

2013-01-01

Pucciniamonoica is a spectacular plant parasitic rust fungus that triggers the formation of flower-like structures (pseudoflowers) in its Brassicaceae host plant Boecherastricta. Pseudoflowers mimic in shape, color, nectar and scent co-occurring and unrelated flowers such as buttercups. They act to attract insects thereby aiding spore dispersal and sexual reproduction of the rust fungus. Although much ecological research has been performed on P. monoica-induced pseudoflowers, this system has yet to be investigated at the molecular or genomic level. To date, the molecular alterations underlying the development of pseudoflowers and the genes involved have not been described. To address this, we performed gene expression profiling to reveal 256 plant biological processes that are significantly altered in pseudoflowers. Among these biological processes, plant genes involved in cell fate specification, regulation of transcription, reproduction, floral organ development, anthocyanin (major floral pigments) and terpenoid biosynthesis (major floral volatile compounds) were down-regulated in pseudoflowers. In contrast, plant genes involved in shoot, cotyledon and leaf development, carbohydrate transport, wax biosynthesis, cutin transport and L-phenylalanine metabolism (pathway that results in phenylethanol and phenylacetaldehyde volatile production) were up-regulated. These findings point to an extensive reprogramming of host genes by the rust pathogen to induce floral mimicry. We also highlight 31 differentially regulated plant genes that are enriched in the biological processes mentioned above, and are potentially involved in the formation of pseudoflowers. This work illustrates the complex perturbations induced by rust pathogens in their host plants, and provides a starting point for understanding the molecular mechanisms of pathogen-induced floral mimicry.

Huanglongbing impairs the rhizosphere-to-rhizoplane enrichment process of the citrus root-associated microbiome.

PubMed

Zhang, Yunzeng; Xu, Jin; Riera, Nadia; Jin, Tao; Li, Jinyun; Wang, Nian

2017-08-10

Roots are the primary site for plant-microbe interactions. Among the three root-associated layers (i.e., rhizosphere, rhizoplane, and endorhiza), the rhizoplane is a key component serving a critical gating role that controls microbial entry into plant roots. The microbial communities colonizing the three layers are believed to be gradually enriched from the bulk soil inoculum. However, it is unknown how this enrichment process, particularly the rhizosphere to rhizoplane step, is affected by biotic stresses, such as disease. In this study, we address this question using the citrus root-associated microbiome as a model. We identified the rhizosphere-to-rhizoplane-enriched taxonomic and functional properties of the citrus root-associated microbiome and determined how they were affected by Huanglongbing (HLB), a severe systemic disease caused by Candidatus Liberibacter asiaticus, using metagenomic and metatranscriptomic approaches. Multiple rhizoplane-enriched genera were identified, with Bradyrhizobium and Burkholderia being the most dominant. Plant-derived carbon sources are an important driving force for the enrichment process. The enrichment of functional attributes, such as motility, chemotaxis, secretion systems, and lipopolysaccharide (LPS) synthesis, demonstrated more active microbe-plant interactions on the rhizoplane than the rhizosphere. We observed that HLB impaired the rhizosphere-to-rhizoplane enrichment process of the citrus root-associated microbiome in three ways: (1) by decreasing the relative abundance of most rhizoplane-enriched genera; (2) by reducing the relative abundance and/or expression activity of the functional attributes involved in microbe-plant interactions; and (3) by recruiting more functional features involved in autotrophic life cycle adaptation, such as carbon fixation and nitrogen nitrification in the HLB rhizoplane microbiome. Finally, our data showed that inoculation of Burkholderia strains isolated from the healthy citrus root-associated microbiome could trigger the expression of genes involved in induced systemic resistance in inoculated plants. HLB causes decreased relative abundance and/or expression activity of rhizoplane-enriched taxonomic and functional properties, collectively resulting in impaired plant host-microbiome interactions. Manipulation of the citrus root-associated microbiome, for instance, by inoculating citrus roots with beneficial Burkholderia strains, has potential to promote plant health. Our results provide novel insights for understanding the contributions of the community enrichment process of the root-associated microbiome to the plant hosts.

Specific Adhesion of Lipid Membranes Can Simultaneously Produce Two Types of Lipid and Protein Heterogeneities

NASA Astrophysics Data System (ADS)

Shindell, Orrin; Micah, Natalie; Ritzer, Max; Gordon, Vernita

2015-03-01

Living cells adhere to one another and their environment. Adhesion is associated with re-organization of the lipid and protein components of the cell membrane. The resulting heterogeneities are functional structures involved in biological processes. We use artificial lipid membranes that contain a single type of binding protein. Before adhesion, the lipid, protein, and dye components in the membrane are well-mixed and constitute a single disordered-liquid phase (Ld) . After adhesion, two distinct types of heterogeneities coexist in the adhesion zone: a central domain of ordered lipid phase that excludes both binding proteins and membrane dye, and a peripheral domain of disordered lipid phase that is densely packed with adhesion proteins and enriched in membrane dye relative to the non-adhered portion of the vesicle. Thus, we show that adhesion that is mediated by only one type of protein can organize the lipid and protein components of the membranes into heterogeneities that resemble those found in biology, for example the immune synapse.

Evaluating Kinase ATP Uptake and Tyrosine Phosphorylation using Multiplexed Quantification of Chemically Labeled and Post-Translationally Modified Peptides

PubMed Central

Fang, Bin; Hoffman, Melissa A.; Mirza, Abu-Sayeef; Mishall, Katie M.; Li, Jiannong; Peterman, Scott M.; Smalley, Keiran S. M.; Shain, Kenneth H.; Weinberger, Paul M.; Wu, Jie; Rix, Uwe; Haura, Eric B.; Koomen, John M.

2015-01-01

Cancer biologists and other healthcare researchers face an increasing challenge in addressing the molecular complexity of disease. Biomarker measurement tools and techniques now contribute to both basic science and translational research. In particular, liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) for multiplexed measurements of protein biomarkers has emerged as a versatile tool for systems biology. Assays can be developed for specific peptides that report on protein expression, mutation, or post-translational modification; discovery proteomics data rapidly translated into multiplexed quantitative approaches. Complementary advances in affinity purification enrich classes of enzymes or peptides representing post-translationally modified or chemically labeled substrates. Here, we illustrate the process for the relative quantification of hundreds of peptides in a single LC-MRM experiment. Desthiobiotinylated peptides produced by activity-based protein profiling (ABPP) using ATP probes and tyrosine-phosphorylated peptides are used as examples. These targeted quantification panels can be applied to further understand the biology of human disease. PMID:25782629

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

PubMed

Ferreira, Manuel A; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; van Dongen, Jenny; Lu, Yi; Rüschendorf, Franz; Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik K E; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-12-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10 -8 ), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

PubMed Central

Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik KE; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-01-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. To identify shared risk variants, we performed a genome-wide association study (GWAS, n=360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P<3x10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes. PMID:29083406

A chemical proteomics approach for global analysis of lysine monomethylome profiling.

PubMed

Wu, Zhixiang; Cheng, Zhongyi; Sun, Mingwei; Wan, Xuelian; Liu, Ping; He, Tieming; Tan, Minjia; Zhao, Yingming

2015-02-01

Methylation of lysine residues on histone proteins is known to play an important role in chromatin structure and function. However, non-histone protein substrates of this modification remain largely unknown. An effective approach for system-wide analysis of protein lysine methylation, particularly lysine monomethylation, is lacking. Here we describe a chemical proteomics approach for global screening for monomethyllysine substrates, involving chemical propionylation of monomethylated lysine, affinity enrichment of the modified monomethylated peptides, and HPLC/MS/MS analysis. Using this approach, we identified with high confidence 446 lysine monomethylation sites in 398 proteins, including three previously unknown histone monomethylation marks, representing the largest data set of protein lysine monomethylation described to date. Our data not only confirms previously discovered lysine methylation substrates in the nucleus and spliceosome, but also reveals new substrates associated with diverse biological processes. This method hence offers a powerful approach for dynamic study of protein lysine monomethylation under diverse cellular conditions and in human diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

DEsubs: an R package for flexible identification of differentially expressed subpathways using RNA-seq experiments.

PubMed

Vrahatis, Aristidis G; Balomenos, Panos; Tsakalidis, Athanasios K; Bezerianos, Anastasios

2016-12-15

DEsubs is a network-based systems biology R package that extracts disease-perturbed subpathways within a pathway network as recorded by RNA-seq experiments. It contains an extensive and customized framework with a broad range of operation modes at all stages of the subpathway analysis, enabling so a case-specific approach. The operation modes include pathway network construction and processing, subpathway extraction, visualization and enrichment analysis with regard to various biological and pharmacological features. Its capabilities render DEsubs a tool-guide for both the modeler and experimentalist for the identification of more robust systems-level drug targets and biomarkers for complex diseases. DEsubs is implemented as an R package following Bioconductor guidelines: http://bioconductor.org/packages/DEsubs/ CONTACT: tassos.bezerianos@nus.edu.sgSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Generating Focused Molecule Libraries for Drug Discovery with Recurrent Neural Networks

PubMed Central

2017-01-01

In de novo drug design, computational strategies are used to generate novel molecules with good affinity to the desired biological target. In this work, we show that recurrent neural networks can be trained as generative models for molecular structures, similar to statistical language models in natural language processing. We demonstrate that the properties of the generated molecules correlate very well with the properties of the molecules used to train the model. In order to enrich libraries with molecules active toward a given biological target, we propose to fine-tune the model with small sets of molecules, which are known to be active against that target. Against Staphylococcus aureus, the model reproduced 14% of 6051 hold-out test molecules that medicinal chemists designed, whereas against Plasmodium falciparum (Malaria), it reproduced 28% of 1240 test molecules. When coupled with a scoring function, our model can perform the complete de novo drug design cycle to generate large sets of novel molecules for drug discovery. PMID:29392184

Bioinformatics analysis of differentially expressed gene profiles associated with systemic lupus erythematosus

PubMed Central

Wu, Chengjiang; Zhao, Yangjing; Lin, Yu; Yang, Xinxin; Yan, Meina; Min, Yujiao; Pan, Zihui; Xia, Sheng; Shao, Qixiang

2018-01-01

DNA microarray and high-throughput sequencing have been widely used to identify the differentially expressed genes (DEGs) in systemic lupus erythematosus (SLE). However, the big data from gene microarrays are also challenging to work with in terms of analysis and processing. The presents study combined data from the microarray expression profile (GSE65391) and bioinformatics analysis to identify the key genes and cellular pathways in SLE. Gene ontology (GO) and cellular pathway enrichment analyses of DEGs were performed to investigate significantly enriched pathways. A protein-protein interaction network was constructed to determine the key genes in the occurrence and development of SLE. A total of 310 DEGs were identified in SLE, including 193 upregulated genes and 117 downregulated genes. GO analysis revealed that the most significant biological process of DEGs was immune system process. Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these DEGs were enriched in signaling pathways associated with the immune system, including the RIG-I-like receptor signaling pathway, intestinal immune network for IgA production, antigen processing and presentation and the toll-like receptor signaling pathway. The current study screened the top 10 genes with higher degrees as hub genes, which included 2′-5′-oligoadenylate synthetase 1, MX dynamin like GTPase 2, interferon induced protein with tetratricopeptide repeats 1, interferon regulatory factor 7, interferon induced with helicase C domain 1, signal transducer and activator of transcription 1, ISG15 ubiquitin-like modifier, DExD/H-box helicase 58, interferon induced protein with tetratricopeptide repeats 3 and 2′-5′-oligoadenylate synthetase 2. Module analysis revealed that these hub genes were also involved in the RIG-I-like receptor signaling, cytosolic DNA-sensing, toll-like receptor signaling and ribosome biogenesis pathways. In addition, these hub genes, from different probe sets, exhibited significant co-expressed tendency in multi-experiment microarray datasets (P<0.01). In conclusion, these key genes and cellular pathways may improve the current understanding of the underlying mechanism of development of SLE. These key genes may be potential biomarkers of diagnosis, therapy and prognosis for SLE. PMID:29257335

Sex differences in panic-relevant responding to a 10% carbon dioxide-enriched air biological challenge.

PubMed

Nillni, Yael I; Berenz, Erin C; Rohan, Kelly J; Zvolensky, Michael J

2012-01-01

The current study examined sex differences in psychological (i.e., self-reported anxiety, panic symptoms, and avoidance) and physiological (i.e., heart rate and skin conductance level) response to, and recovery from, a laboratory biological challenge. Participants were a community-recruited sample of 128 adults (63.3% women; M(age)=23.2 years, SD=8.9) who underwent a 4-min 10% CO(2)-enriched air biological challenge. As predicted, women reported more severe physical panic symptoms and avoidance (i.e., less willingness to participate in another challenge) and demonstrated increased heart rate as compared to men above and beyond the variance accounted for by other theoretically relevant variables (recent panic attack history, neuroticism, and anxiety sensitivity). Additionally, women demonstrated a faster rate of recovery with respect to heart rate compared to men. These results are in line with literature documenting sex-specific differences in panic psychopathology, and results are discussed in the context of possible mechanisms underlying sex differences in panic vulnerability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Production of dissolved organic carbon enriched in deoxy sugars representing an additional sink for biological C drawdown in the Amazon River plume

NASA Astrophysics Data System (ADS)

Meador, Travis B.; Aluwihare, Lihini I.

2014-10-01

In North Atlantic waters impacted by discharges from the Amazon and Orinoco Rivers, where planktonic diatom-diazotroph associations (DDA) were active, we observed that an average (± standard deviation) of 61 ± 12% of the biological drawdown of dissolved inorganic carbon (DIC) was partitioned into the accumulating total organic carbon pool, representing a flux of up to 9 ± 4 Tg C yr-1. This drawdown corresponded with chemical alteration of ultrafiltered dissolved organic matter (UDOM), including increases in stable C isotopic composition (δ13C) and C:N. The dissolved carbohydrate component of UDOM also increased with biological DIC drawdown and diatom-associated diazotroph (i.e., Richelia) abundance. New carbohydrates could be distinguished by distinctively high relative abundances of deoxy sugars (up to 55% of monosaccharides), which may promote aggregate formation and enhance vertical carbon export. The identified production of non-Redfieldian, C-enriched UDOM thus suggests a mechanism to explain enhanced C sequestration associated with DDA N2 fixation, which may be widespread in mesohaline environments.

Identification of a Conserved Glycan Signature for Microvesicles

PubMed Central

Batista, Bianca S.; Eng, William S.; Pilobello, Kanoelani T.; Hendricks-Muñoz, Karen D.; Mahal, Lara K.

2011-01-01

Microvesicles (exosomes) are important mediators of intercellular communication, playing a role in immune regulation, cancer progression and the spread of infectious agents. The biological functions of these small vesicles are dependent upon their composition, which is regulated by mechanisms that are not well understood. Although numerous proteomic studies of these particles exist, little is known about their glycosylation. Carbohydrates are involved in protein trafficking and cellular recognition. Glycomic analysis may thus provide valuable insights into microvesicle biology. In this study, we analyzed glycosylation patterns of microvesicles derived from a variety of biological sources using lectin microarray technology. Comparison of the microvesicle glycomes with their parent cell membranes revealed both enrichment and depletion of specific glycan epitopes in these particles. These include enrichment in high mannose, polylactosamine, α-2,6 sialic acid, and complex N-linked glycans and exclusion of terminal blood group A and B antigens. The polylactosamine signature derives from distinct glycoprotein cohorts in microvesicles of different origins. Taken together our data point to the emergence of microvesicles from a specific membrane microdomain, implying a role for glycosylation in microvesicle protein sorting. PMID:21859146

Shape Transitions and Lattice Structuring of Ceramide-Enriched Domains Generated by Sphingomyelinase in Lipid Monolayers

PubMed Central

Härtel, Steffen; Fanani, María Laura; Maggio, Bruno

2005-01-01

Sphingomyelinases (SMases) hydrolyze the membrane constituent sphingomyelin (SM) to phosphocholine and ceramide (Cer). Growing evidence supports that SMase-induced SM→Cer conversion leads to the formation of lateral Cer-enriched domains which drive structural reorganization in lipid membranes. We previously provided visual evidence in real-time for the formation of Cer-enriched domains in SM monolayers through the action of the neutral Bacillus cereus SMase. In this work, we disclose a succession of discrete morphologic transitions and lateral organization of Cer-enriched domains that underlay the SMase-generated surface topography. We further reveal how these structural parameters couple to the generation of two-dimensional electrostatic fields, based upon the specific orientation of the lipid dipole moments in the Cer-enriched domains. Advanced image processing routines in combination with time-resolved epifluorescence microscopy on Langmuir monolayers revealed: 1), spontaneous nucleation and circular growth of Cer-enriched domains after injection of SMase into the subphase of the SM monolayer; 2), domain-intrinsic discrete transitions from circular to periodically undulating shapes followed by a second transition toward increasingly branched morphologies; 3), lateral superstructure organization into predominantly hexagonal domain lattices; 4), formation of super-superstructures by the hexagonal lattices; and 5), rotationally and laterally coupled domain movement before domain border contact. All patterns proved to be specific for the SMase-driven system since they could not be observed with Cer-enriched domains generated by defined mixtures of SM/Cer in enzyme-free monolayers at the same surface pressure (Π = 10 mN/m). Following the theories of lateral shape transitions, dipolar electrostatic interactions of lipid domains, and direct determinations of the monolayer dipole potential, our data show that SMase induces a domain-specific packing and orientation of the molecular dipole moments perpendicular to the air/water interface. In consequence, protein-driven generation of specific out-of-equilibrium states, an accepted concept for maintenance of transmembrane lipid asymmetry, must also be considered on the lateral level. Lateral enzyme-specific out-of-equilibrium organization of lipid domains represents a new level of signal transduction from local (nm) to long-range (μm) scales. The cross-talk between lateral domain structures and dipolar electrostatic fields adds new perspectives to the mechanisms of SMase-mediated signal transduction in biological membranes. PMID:15489298

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

PubMed

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

Reorganization in processing of spectral and temporal input in the rat posterior auditory field induced by environmental enrichment

PubMed Central

Jakkamsetti, Vikram; Chang, Kevin Q.

2012-01-01

Environmental enrichment induces powerful changes in the adult cerebral cortex. Studies in primary sensory cortex have observed that environmental enrichment modulates neuronal response strength, selectivity, speed of response, and synchronization to rapid sensory input. Other reports suggest that nonprimary sensory fields are more plastic than primary sensory cortex. The consequences of environmental enrichment on information processing in nonprimary sensory cortex have yet to be studied. Here we examine physiological effects of enrichment in the posterior auditory field (PAF), a field distinguished from primary auditory cortex (A1) by wider receptive fields, slower response times, and a greater preference for slowly modulated sounds. Environmental enrichment induced a significant increase in spectral and temporal selectivity in PAF. PAF neurons exhibited narrower receptive fields and responded significantly faster and for a briefer period to sounds after enrichment. Enrichment increased time-locking to rapidly successive sensory input in PAF neurons. Compared with previous enrichment studies in A1, we observe a greater magnitude of reorganization in PAF after environmental enrichment. Along with other reports observing greater reorganization in nonprimary sensory cortex, our results in PAF suggest that nonprimary fields might have a greater capacity for reorganization compared with primary fields. PMID:22131375

Determination of (2)H-enrichment of rat brain interstitial fluid and rat plasma by headspace-gas-chromatography - quadrupole-mass-spectrometry.

PubMed

Eberl, Anita; Altendorfer-Kroath, Thomas; Kollmann, Denise; Birngruber, Thomas; Sinner, Frank; Raml, Reingard; Magnes, Christoph

2016-09-15

(2)H2O as nonradioactive, stable marker substance is commonly used in preclinical and clinical studies and the precise determination of (2)H2O concentration in biological samples is crucial. However, aside from isotope ratio mass spectrometry (IRMS), only a very limited number of methods to accurately measure the (2)H2O concentration in biological samples are routinely established until now. In this study, we present a straightforward method to accurately measure (2)H-enrichment of rat brain interstitial fluid (ISF) and rat plasma to determine the relative recovery of a cerebral open flow microperfusion (cOFM) probe, using headspace-gas-chromatography - quadrupole-mass-spectrometry. This method is based on basic-catalyzed hydrogen/deuterium exchange in acetone and detects the (2)H-labelled acetone directly by the headspace GC-MS. Small sample volumes and limited number of preparation steps make this method highly competitive. It has been fully validated. (2)H enriched to 8800 ppm in plasma showed an accuracy of 98.9% and %Relative Standard Deviation (RSD) of 3.1 with n = 18 over three days and with two operators. Similar performance was obtained for cerebral ISF enriched to 1100 ppm (accuracy: 96.5%, %RSD: 3.1). With this highly reproducible method we demonstrated the successful employment of (2)H2O as performance marker for a cOFM probe. Copyright © 2016. Published by Elsevier Inc.

Theory of Inpatient Circadian Care (TICC): A Proposal for a Middle-Range Theory

PubMed Central

Camargo-Sanchez, Andrés; Niño, Carmen L; Sánchez, Leonardo; Echeverri, Sonia; Gutiérrez, Diana P; Duque, Andrés F; Pianeta, Oscar; Jaramillo-Gómez, Jenny A; Pilonieta, Martin A; Cataño, Nhora; Arboleda, Humberto; Agostino, Patricia V; Alvarez-Baron, Claudia P; Vargas, Rafael

2015-01-01

The circadian system controls the daily rhythms of a variety of physiological processes. Most organisms show physiological, metabolic and behavioral rhythms that are coupled to environmental signals. In humans, the main synchronizer is the light/dark cycle, although non-photic cues such as food availability, noise, and work schedules are also involved. In a continuously operating hospital, the lack of rhythmicity in these elements can alter the patient’s biological rhythms and resilience. This paper presents a Theory of Inpatient Circadian Care (TICC) grounded in circadian principles. We conducted a literature search on biological rhythms, chronobiology, nursing care, and middle-range theories in the databases PubMed, SciELO Public Health, and Google Scholar. The search was performed considering a period of 6 decades from 1950 to 2013. Information was analyzed to look for links between chronobiology concepts and characteristics of inpatient care. TICC aims to integrate multidisciplinary knowledge of biomedical sciences and apply it to clinical practice in a formal way. The conceptual points of this theory are supported by abundant literature related to disease and altered biological rhythms. Our theory will be able to enrich current and future professional practice. PMID:25767632

On the integration of protein-protein interaction networks with gene expression and 3D structural data: What can be gained?

NASA Astrophysics Data System (ADS)

Bertolazzi, Paola; Bock, Mary Ellen; Guerra, Concettina; Paci, Paola; Santoni, Daniele

2014-06-01

The biological role of proteins has been analyzed from different perspectives, initially by considering proteins as isolated biological entities, then as cooperating entities that perform their function by interacting with other molecules. There are other dimensions that are important for the complete understanding of the biological processes: time and location. However a protein is rarely annotated with temporal and spatial information. Experimental Protein-Proteins Interaction (PPI) data are static; furthermore they generally do not include transient interactions which are a considerable fraction of the interactome of many organisms. One way to incorporate temporal and condition information is to use other sources of information, such as gene expression data and 3D structural data. Here we review work done to understand the insight that can be gained by enriching PPI data with gene expression and 3D structural data. In particular, we address the following questions: Can the dynamics of a single protein or of an interaction be accurately derived from these data? Can the assembly-disassembly of protein complexes be traced over time? What type of topological changes occur in a PPI network architecture over time?

Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

PubMed

Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

2014-01-01

The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

PubMed Central

Lin, Jhih-Rong; Cai, Ying; Zhang, Quanwei; Zhang, Wen; Nogales-Cadenas, Rubén; Zhang, Zhengdong D.

2016-01-01

Schizophrenia is a severe mental disorder with a large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, the underlying biological mechanisms are not clear. The critical first step for their elucidation is to identify the most likely disease genes as the source of the association signals. Here, we describe a general computational framework of post-GWAS analysis for complex disease gene prioritization. We identify 132 putative schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are outside the risk regions, likely under regulation of transcriptional regulatory elements contained therein. These putative schizophrenia risk genes are transcriptionally active in both brain and the immune system, and highly enriched among cellular pathways, consistent with leading pathophysiological hypotheses about the pathogenesis of schizophrenia. With their involvement in distinct biological processes, these putative schizophrenia risk genes, with different association strengths, show distinctive temporal expression patterns, and play specific biological roles during brain development. PMID:27754856

The role of domain-general cognitive resources in children's construction of a vitalist theory of biology.

PubMed

Bascandziev, Igor; Tardiff, Nathan; Zaitchik, Deborah; Carey, Susan

2018-08-01

Some episodes of learning are easier than others. Preschoolers can learn certain facts, such as "my grandmother gave me this purse," only after one or two exposures (easy to learn; fast mapping), but they require several years to learn that plants are alive or that the sun is not alive (hard to learn). One difference between the two kinds of knowledge acquisition is that hard cases often require conceptual construction, such as the construction of the biological concept alive, whereas easy cases merely involve forming new beliefs formulated over concepts the child already has (belief revision, a form of knowledge enrichment). We asked whether different domain-general cognitive resources support these two types of knowledge acquisition (conceptual construction and knowledge enrichment that supports fast mapping) by testing 82 6-year-olds in a pre-training/training/post-training study. We measured children's improvement in an episode involving theory construction (the beginning steps of acquisition of the framework theory of vitalist biology, which requires conceptual change) and in an episode involving knowledge enrichment alone (acquisition of little known facts about animals, such as the location of crickets' ears and the color of octopus blood). In addition, we measured children's executive functions and receptive vocabulary to directly compare the resources drawn upon in the two episodes of learning. We replicated and extended previous findings highlighting the differences between conceptual construction and knowledge enrichment, and we found that Executive Functions predict improvement on the Vitalism battery but not on the Fun Facts battery and that Receptive Vocabulary predicts improvement the Fun Facts battery but not on the Vitalism battery. This double dissociation provides new evidence for the distinction between the two types of knowledge acquisition, and bears on the nature of the learning mechanisms involved in each. Copyright © 2018 Elsevier Inc. All rights reserved.

Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

PubMed Central

Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

2012-01-01

First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This dataset represents a rich source of testable hypotheses regarding the biological mechanisms of ErbB receptors. PMID:22973453

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication.

PubMed

Montague, Michael J; Li, Gang; Gandolfi, Barbara; Khan, Razib; Aken, Bronwen L; Searle, Steven M J; Minx, Patrick; Hillier, LaDeana W; Koboldt, Daniel C; Davis, Brian W; Driscoll, Carlos A; Barr, Christina S; Blackistone, Kevin; Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas; Alkan, Can; Thomas, Gregg W C; Hahn, Matthew W; Menotti-Raymond, Marilyn; O'Brien, Stephen J; Wilson, Richard K; Lyons, Leslie A; Murphy, William J; Warren, Wesley C

2014-12-02

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

PubMed Central

Li, Gang; Gandolfi, Barbara; Khan, Razib; Aken, Bronwen L.; Searle, Steven M. J.; Minx, Patrick; Hillier, LaDeana W.; Koboldt, Daniel C.; Davis, Brian W.; Driscoll, Carlos A.; Barr, Christina S.; Blackistone, Kevin; Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas; Alkan, Can; Thomas, Gregg W. C.; Hahn, Matthew W.; Menotti-Raymond, Marilyn; O’Brien, Stephen J.; Wilson, Richard K.; Lyons, Leslie A.; Murphy, William J.; Warren, Wesley C.

2014-01-01

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae. PMID:25385592

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF

PubMed Central

Cong, Yingnan; Chan, Yao-ban; Phillips, Charles A.; Langston, Michael A.; Ragan, Mark A.

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k. Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k. PMID:28154557

Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

NASA Astrophysics Data System (ADS)

Li, Yue; Zhang, Zhaolei

2014-11-01

Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis.

PubMed

Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A; Vernieri, Paolo; Ferrante, Antonio

2016-10-01

Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Enrichment scale determines herbivore control of primary producers.

PubMed

Gil, Michael A; Jiao, Jing; Osenberg, Craig W

2016-03-01

Anthropogenic nutrient enrichment stimulates primary production and threatens natural communities worldwide. Herbivores may counteract deleterious effects of enrichment by increasing their consumption of primary producers. However, field tests of herbivore control are often done by adding nutrients at small (e.g., sub-meter) scales, while enrichment in real systems often occurs at much larger scales (e.g., kilometers). Therefore, experimental results may be driven by processes that are not relevant at larger scales. Using a mathematical model, we show that herbivores can control primary producer biomass in experiments by concentrating their foraging in small enriched plots; however, at larger, realistic scales, the same mechanism may not lead to herbivore control of primary producers. Instead, other demographic mechanisms are required, but these are not examined in most field studies (and may not operate in many systems). This mismatch between experiments and natural processes suggests that many ecosystems may be less resilient to degradation via enrichment than previously believed.

Direction discovery: A science enrichment program for high school students.

PubMed

Sikes, Suzanne S; Schwartz-Bloom, Rochelle D

2009-03-01

Launch into education about pharmacology (LEAP) is an inquiry-based science enrichment program designed to enhance competence in biology and chemistry and foster interest in science careers especially among under-represented minorities. The study of how drugs work, how they enter cells, alter body chemistry, and exit the body engages students to conceptualize fundamental precepts in biology, chemistry, and math. Students complete an intensive three-week course in the fundamentals of pharmacology during the summer followed by a mentored research component during the school year. Following a 5E learning paradigm, the summer course captures student interest by introducing controversial topics in pharmacology and provides a framework that guides them to explore topics in greater detail. The 5E learning cycle is recapitulated as students extend their knowledge to design and to test an original research question in pharmacology. LEAP students demonstrated significant gains in biology and chemistry knowledge and interests in pursuing science. Several students earned honors for the presentation of their research in regional and state science fairs. Success of the LEAP model in its initial 2 years argues that coupling college-level coursework of interest to teens with an authentic research experience enhances high school student success in and enthusiasm for science. Copyright © 2009 International Union of Biochemistry and Molecular Biology, Inc.

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PubMed

Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

2014-01-01

Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

On the impact of neutron star binaries' natal-kick distribution on the Galactic r-process enrichment

NASA Astrophysics Data System (ADS)

Safarzadeh, Mohammadtaher; Côté, Benoit

2017-11-01

We study the impact of the neutron star binaries' (NSBs) natal-kick distribution on the galactic r-process enrichment. We model the growth of a Milky Way type halo based on N-body simulation results and its star formation history based on multi-epoch abundance matching techniques. We consider that the NSBs that merge well beyond the galaxy's effective radius (>2 × Reff) do not contribute to the galactic r-process enrichment. Assuming a power-law delay-time distribution (DTD) function (∝t-1) with tmin = 30 Myr for binaries' coalescence time-scales and an exponential profile for their natal-kick distribution with an average value of 180 km s-1, we show that up to ˜ 40 per cent of all formed NSBs do not contribute to the r-process enrichment by z = 0, either because they merge far from the galaxy at a given redshift (up to ˜ 25 per cent) or have not yet merged by today (˜ 15 per cent). Our result is largely insensitive to the details of the DTD function. Assuming a constant coalescence time-scale of 100 Myr well approximates the adopted DTD although with 30 per cent of the NSBs ending up not contributing to the r-process enrichment. Our results, although rather dependent on the adopted natal-kick distribution, represent the first step towards estimating the impact of natal kicks and DTD functions on the r-process enrichment of galaxies that would need to be incorporated in the hydrodynamical simulations.

Feeding the pipeline: academic skills training for predental students.

PubMed

Markel, Geraldine; Woolfolk, Marilyn; Inglehart, Marita Rohr

2008-06-01

This article reports the outcomes of an evaluation conducted to determine if an academic skills training program for undergraduate predental students from underrepresented minority backgrounds increased the students' standardized academic skills test scores for vocabulary, reading comprehension, reading rates, spelling, and math as well as subject-specific test results in biology, chemistry, and physics. Data from standardized academic skill tests and subject-specific tests were collected at the beginning and end of the 1998 to 2006 Pipeline Programs, six-week summer enrichment programs for undergraduate predental students from disadvantaged backgrounds. In total, 179 students (75.4 percent African American, 7.3 percent Hispanic, 5.6 percent Asian American, 5 percent white) attended the programs during these nine summers. Scores on the Nelson-Denny Reading Test showed that the students improved their vocabulary scores (percentile ranks before/after: 46.80 percent/59.56 percent; p<.001), reading comprehension scores (47.21 percent/62.67 percent; p<.001), and reading rates (34.01 percent/78.31 percent; p<.001) from the beginning to the end of the summer programs. Results on the Wide Range Achievement Test III showed increases in spelling (73.58 percent/86.22 percent; p<.001) and math scores (56.98 percent/81.28 percent; p<.001). The students also improved their subject-specific scores in biology (39.07 percent/63.42 percent; p<.001), chemistry (20.54 percent/51.01 percent; p<.001), and physics (35.12 percent/61.14 percent; p<.001). To increase the number of underrepresented minority students in the dental school admissions pool, efforts are needed to prepare students from disadvantaged backgrounds for this process. These data demonstrate that a six-week enrichment program significantly improved the academic skills and basic science knowledge scores of undergraduate predental students. These improvements have the potential to enhance the performance of these students in college courses and thus increase their level of competitiveness in the dental school admissions process.

Multivariate Genetic Correlates of the Auditory Paired Stimuli-Based P2 Event-Related Potential in the Psychosis Dimension From the BSNIP Study.

PubMed

Mokhtari, Mohammadreza; Narayanan, Balaji; Hamm, Jordan P; Soh, Pauline; Calhoun, Vince D; Ruaño, Gualberto; Kocherla, Mohan; Windemuth, Andreas; Clementz, Brett A; Tamminga, Carol A; Sweeney, John A; Keshavan, Matcheri S; Pearlson, Godfrey D

2016-05-01

The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Minimum Nuclear Deterrence Postures in South Asia: An Overview

DTIC Science & Technology

2001-10-01

states in May 1998, India and Pakistan both espoused nuclear restraint. Their senior officials soon embraced the language of "minimum credible...Air Force and Army. India’s longer-range nuclear-capable missiles such as the Agni, however, are still in the research and development process under...explained in Appendix A, Pakistan continued between 1991 and 1998 to enrich uranium to low- enriched (LEU) levels. Since enrichment is an iterative process

Incorporating Information of microRNAs into Pathway Analysis in a Genome-Wide Association Study of Bipolar Disorder

PubMed Central

Shih, Wei-Liang; Kao, Chung-Feng; Chuang, Li-Chung; Kuo, Po-Hsiu

2012-01-01

MicroRNAs (miRNAs) are known to be important post-transcriptional regulators that are involved in the etiology of complex psychiatric traits. The present study aimed to incorporate miRNAs information into pathway analysis using a genome-wide association dataset to identify relevant biological pathways for bipolar disorder (BPD). We selected psychiatric- and neurological-associated miRNAs (N = 157) from PhenomiR database. The miRNA target genes (miTG) predictions were obtained from microRNA.org. Canonical pathways (N = 4,051) were downloaded from the Molecule Signature Database. We employed a novel weighting scheme for miTGs in pathway analysis using methods of gene set enrichment analysis and sum-statistic. Under four statistical scenarios, 38 significantly enriched pathways (P-value < 0.01 after multiple testing correction) were identified for the risk of developing BPD, including pathways of ion channels associated (e.g., gated channel activity, ion transmembrane transporter activity, and ion channel activity) and nervous related biological processes (e.g., nervous system development, cytoskeleton, and neuroactive ligand receptor interaction). Among them, 19 were identified only when the weighting scheme was applied. Many miRNA-targeted genes were functionally related to ion channels, collagen, and axonal growth and guidance that have been suggested to be associated with BPD previously. Some of these genes are linked to the regulation of miRNA machinery in the literature. Our findings provide support for the potential involvement of miRNAs in the psychopathology of BPD. Further investigations to elucidate the functions and mechanisms of identified candidate pathways are needed. PMID:23264780

MicroRNA Expression Profiling in CCl4-Induced Liver Fibrosis of Mus musculus

PubMed Central

Hyun, Jeongeun; Park, Jungwook; Wang, Sihyung; Kim, Jieun; Lee, Hyun-Hee; Seo, Young-Su; Jung, Youngmi

2016-01-01

Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl4) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis. Herein, we found that four miRNAs were upregulated and four miRNAs were downregulated more than two-fold in CCl4-treated livers compared to a control liver. Eight miRNAs were predicted to target a total of 4079 genes. GO analysis revealed that those target genes were located in various cellular compartments, including cytoplasm, nucleolus and cell surface, and they were involved in protein-protein or protein-DNA bindings, which influence the signal transductions and gene transcription. Furthermore, pathway enrichment analysis demonstrated that the 72 subspecialized signaling pathways were associated with CCl4-induced liver fibrosis and were mostly classified into metabolic function-related pathways. These results suggest that CCl4 induces liver fibrosis by disrupting the metabolic pathways. In conclusion, we presented several miRNAs and their biological processes that might be important in the progression of liver fibrosis; these findings help increase the understanding of liver fibrogenesis and provide novel ideas for further studies of the role of miRNAs in liver fibrosis. PMID:27322257

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Genetically contextual effects of smoking on genome wide DNA methylation.

PubMed

Dogan, Meeshanthini V; Beach, Steven R H; Philibert, Robert A

2017-09-01

Smoking is the leading cause of death in the United States. It exerts its effects by increasing susceptibility to a variety of complex disorders among those who smoke, and if pregnant, to their unborn children. In prior efforts to understand the epigenetic mechanisms through which this increased vulnerability is conveyed, a number of investigators have conducted genome wide methylation analyses. Unfortunately, secondary to methodological limitations, these studies were unable to examine methylation in gene regions with significant amounts of genetic variation. Using genome wide genetic and epigenetic data from the Framingham Heart Study, we re-examined the relationship of smoking status to genome wide methylation status. When only methylation status is considered, smoking was significantly associated with differential methylation in 310 genes that map to a variety of biological process and cellular differentiation pathways. However, when SNP effects on the magnitude of smoking associated methylation changes are also considered, cis and trans-interaction effects were noted at a total of 266 and 4353 genes with no marked enrichment for any biological pathways. Furthermore, the SNP variation participating in the significant interaction effects is enriched for loci previously associated with complex medical illnesses. The enlarged scope of the methylome shown to be affected by smoking may better explicate the mediational pathways linking smoking with a myriad of smoking related complex syndromes. Additionally, these results strongly suggest that combined epigenetic and genetic data analyses may be critical for a more complete understanding of the relationship between environmental variables, such as smoking, and pathophysiological outcomes. © 2017 Wiley Periodicals, Inc.

Enrichment behavior and transport mechanism of soil-bound PAHs during rainfall-runoff events.

PubMed

Zheng, Yi; Luo, Xiaolin; Zhang, Wei; Wu, Bin; Han, Feng; Lin, Zhongrong; Wang, Xuejun

2012-12-01

Polycyclic Aromatic Hydrocarbons (PAHs) transported by surface runoff result in nonpoint source pollution and jeopardize aquatic ecosystems. The transport mechanism of PAHs during rainfall-runoff events has been rarely studied regarding pervious areas. An experimental system was setup to simulate the runoff pollution process on PAHs-contaminated soil. The enrichment behavior of soil-bound PAHs was investigated. The results show that soil organic matters (SOM), rather than clay particles, seem to be the main carrier of PAHs. The enrichment is highly conditioned on runoff and erosion processes, and its magnitude varies among PAH compounds. It is not feasible to build a simple and universal relationship between enrichment ratio and sediment discharge following the traditional enrichment theory. To estimate the flux of PAHs from pervious areas, soil erosion process has to be clearly understood, and both organic carbon content and composition of SOM should be factored into the calculation. Copyright © 2012 Elsevier Ltd. All rights reserved.

HExpoChem: a systems biology resource to explore human exposure to chemicals.

PubMed

Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian; Edsgärd, Daniel; Rigina, Olga; Gupta, Ramneek; Audouze, Karine

2013-05-01

Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical-protein interactions have been enriched with a quality-scored human protein-protein interaction network, a protein-protein association network and a chemical-chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment. HExpoChem is available at http://www.cbs.dtu.dk/services/HExpoChem-1.0/.

Proposed standards for acute exposure to low enrichment uranium for compliance with 10 CFR 70.61.

PubMed

Kathren, Ronald L; Burklin, Richard K

2008-08-01

Title 10, Code of Federal Regulations Part 70, puts forth requirements for licensure of special nuclear material including specific risk criteria for acute intakes based on biological effects. Standards for acute oral and inhalation intakes of soluble low enrichment are proposed for the three levels of biological effects given in the regulations. These levels were developed largely from available human data and have a large measure of conservatism. The proposed threshold for life endangerment was 500 mg for acute inhalation intakes and 2,500 mg for acute ingestion intakes. Acute intakes of 1,400 mg for ingestion and 100 mg for inhalation are proposed as thresholds for irreversible or serious long lasting health effects. For minor transient health effects, the proposed levels are 410 and 30 mg, respectively, for acute ingestion and inhalation intakes. For acute intakes below these levels, no demonstrable toxicological effects are anticipated.

Mars Atmospheric Escape Recorded by H, C and O Isotope Ratios in Carbon Dioxide and Water Measured by the Sam Tunable Laser Spectrometer on the Curiosity Rover

NASA Technical Reports Server (NTRS)

Webster, C. R.; Mahaffy, P. R.; Leshin, L. A.; Atreya, S. K.; Flesch, G. J.; Stern, J.; Christensen, L. E.; Vasavada, A. R.; Owen, T.; Niles, P. B.;

Understanding immunology: fun at an intersection of the physical, life, and clinical sciences

NASA Astrophysics Data System (ADS)

Chakraborty, Arup K.

2014-10-01

Understanding how the immune system works is a grand challenge in science with myriad direct implications for improving human health. The immune system protects us from infectious pathogens and cancer, and maintains a harmonious steady state with essential microbiota in our gut. Vaccination, the medical procedure that has saved more lives than any other, involves manipulating the immune system. Unfortunately, the immune system can also go awry to cause autoimmune diseases. Immune responses are the product of stochastic collective dynamic processes involving many interacting components. These processes span multiple scales of length and time. Thus, statistical mechanics has much to contribute to immunology, and the oeuvre of biological physics will be further enriched if the number of physical scientists interested in immunology continues to increase. I describe how I got interested in immunology and provide a glimpse of my experiences working on immunology using approaches from statistical mechanics and collaborating closely with immunologists.