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Sample records for differentially coexpressed disease

  1. Dissection of regulatory networks that are altered in disease via differential co-expression.

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    David Amar

    Full Text Available Comparing the gene-expression profiles of sick and healthy individuals can help in understanding disease. Such differential expression analysis is a well-established way to find gene sets whose expression is altered in the disease. Recent approaches to gene-expression analysis go a step further and seek differential co-expression patterns, wherein the level of co-expression of a set of genes differs markedly between disease and control samples. Such patterns can arise from a disease-related change in the regulatory mechanism governing that set of genes, and pinpoint dysfunctional regulatory networks. Here we present DICER, a new method for detecting differentially co-expressed gene sets using a novel probabilistic score for differential correlation. DICER goes beyond standard differential co-expression and detects pairs of modules showing differential co-expression. The expression profiles of genes within each module of the pair are correlated across all samples. The correlation between the two modules, however, differs markedly between the disease and normal samples. We show that DICER outperforms the state of the art in terms of significance and interpretability of the detected gene sets. Moreover, the gene sets discovered by DICER manifest regulation by disease-specific microRNA families. In a case study on Alzheimer's disease, DICER dissected biological processes and protein complexes into functional subunits that are differentially co-expressed, thereby revealing inner structures in disease regulatory networks.

  2. A methodology for the analysis of differential coexpression across the human lifespan.

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    Gillis, Jesse; Pavlidis, Paul

    2009-09-22

    Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation

  3. Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs

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    Ye Zhi-Qiang

    2011-08-01

    Full Text Available Abstract Background Differential coexpression analysis (DCEA is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links. Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.

  4. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

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    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  5. Characterization of differentially expressed genes using high-dimensional co-expression networks

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    Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

    2010-01-01

    We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

  6. A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

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    Zhang, Qingyang

    2018-05-16

    Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

  7. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

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    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  8. Gene co-expression networks shed light into diseases of brain iron accumulation.

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    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.

  9. A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

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    Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

    2017-12-20

    Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

  10. Meta-analysis of inter-species liver co-expression networks elucidates traits associated with common human diseases.

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    Kai Wang

    2009-12-01

    Full Text Available Co-expression networks are routinely used to study human diseases like obesity and diabetes. Systematic comparison of these networks between species has the potential to elucidate common mechanisms that are conserved between human and rodent species, as well as those that are species-specific characterizing evolutionary plasticity. We developed a semi-parametric meta-analysis approach for combining gene-gene co-expression relationships across expression profile datasets from multiple species. The simulation results showed that the semi-parametric method is robust against noise. When applied to human, mouse, and rat liver co-expression networks, our method out-performed existing methods in identifying gene pairs with coherent biological functions. We identified a network conserved across species that highlighted cell-cell signaling, cell-adhesion and sterol biosynthesis as main biological processes represented in genome-wide association study candidate gene sets for blood lipid levels. We further developed a heterogeneity statistic to test for network differences among multiple datasets, and demonstrated that genes with species-specific interactions tend to be under positive selection throughout evolution. Finally, we identified a human-specific sub-network regulated by RXRG, which has been validated to play a different role in hyperlipidemia and Type 2 diabetes between human and mouse. Taken together, our approach represents a novel step forward in integrating gene co-expression networks from multiple large scale datasets to leverage not only common information but also differences that are dataset-specific.

  11. Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma

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    Li Z

    2017-06-01

    Full Text Available Zhen Li,1 Qianlan Yao,1 Songjian Zhao,1 Yin Wang,2,3 Yixue Li,1,4 Zhen Wang4 1School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 2Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 3Collaborative Innovation Center for Genetics and Development, Fudan University, 4Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Esophageal squamous cell carcinoma (ESCC is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2 might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5

  12. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

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    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  13. Disease gene characterization through large-scale co-expression analysis.

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    Allen Day

    2009-12-01

    Full Text Available In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET.Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format. The size of Celsius makes UGET a powerful gene characterization tool. Using a small seed list of known cartilage-selective genes, UGET extended the list of known genes by identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested were validated by qPCR including the novel cartilage-specific genes SDK2 and FLJ41170. In addition, we retrospectively tested UGET and other gene expression based prioritization tools to identify disease-causing genes within known linkage intervals. We first demonstrated this utility with UGET using genetically heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric disorders and type 2 limb girdle muscular dystrophy (LGMD2 and then compared UGET to other gene expression based prioritization programs which use small but discrete and well annotated datasets. Finally, we observed a significantly higher gene correlation shared between genes in disease networks associated with similar complex or Mendelian disorders.UGET is an invaluable resource for a geneticist that permits the rapid inclusion of expression criteria from one to hundreds of genes in genomic intervals linked to disease. By using thousands of arrays UGET annotates and prioritizes genes better than other tools especially with rare tissue disorders or complex multi-tissue biological processes. This information can be critical in prioritization of candidate genes for sequence analysis.

  14. A subpopulation of dopaminergic neurons co-expresses serotonin in ventral mesencephalic cultures but not after intrastriatal transplantation in a rat model of Parkinsons disease

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    Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique

    2017-01-01

    Cell replacement therapy is a promising avenue into the investigation and treatment of Parkinson’s disease (PD) and in some cases significant long-term motor improvements have been demonstrated. The main source of donor tissue is the human fetal ventral mesencephalon (VM), which consists...... 30% of the dopaminergic neurons in the donor tissue co-expressed serotonin, no co-localization could be detected in grafts one month after intrastriatal transplantation into hemi-parkinsonian rats. In conclusion, a significant and susceptible sub-population of dopaminergic neurons in fetal VM tissues...... both fetal rat and human dissociated, organotypic and neurosphere VM cultures as well as an animal model of PD were investigated. In dissociated rat VM cultures approximately 30% of the TH positive neurons co-expressed serotonin, while no co-localization with GABA was observed. Interestingly, co...

  15. Differential diagnosis of rheumatic diseases

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    Lingg, G.; Schorn, C.

    2006-01-01

    Which imaging modalities are appropriate for the Differential diagnosis of Rheumatic diseases. MRI has far most the highest sensitivity and is unequaled in its brilliant presentation of Anatomy and Pathology. But it is sometimes forgotten, that this is at least in part the result of carefully selected sequences, dedicated to the expected result. In a method totally independent of any result, this should not be the case. In contrary this method should be highly standardised and regardless what will be the findings. This is true for Plain X-ray. It will be shown, that already the outer silhouette of the soft parts with different features of swelling, and differences in density and even more - defects or appositions of the bony silhouette in the majority of cases at least will allow to classify the patient for a group of diseases and in many cases will lead to a definite diagnosis. Differential diagnoses like Rheumatoid Arthritis versus Psoriatic Arthritis or simply but not always simple - inflammatory Arthritis versus degenerative disease - are allowed to be answered definitely, not always so in MRI. The condition of the subchondral bone can give hints, how advanced and how active the disease is at present. Plain X-ray offers high specifity in the differential diagnoses of Rheumatic diseases, it is well standardised and it is a device, to use independent from any suspected findings. So it is the method of choice for questions of differential diagnosis. This is even more true, thinking of the possibility, to investigate all clinically involved regions with not to much extended efforts, whereas MRI and CT are used normally for only one region. (orig.) [de

  16. Evolution, functional differentiation, and co-expression of the RLK gene family revealed in Jilin ginseng, Panax ginseng C.A. Meyer.

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    Lin, Yanping; Wang, Kangyu; Li, Xiangyu; Sun, Chunyu; Yin, Rui; Wang, Yanfang; Wang, Yi; Zhang, Meiping

    2018-02-21

    Most genes in a genome exist in the form of a gene family; therefore, it is necessary to have knowledge of how a gene family functions to comprehensively understand organismal biology. The receptor-like kinase (RLK)-encoding gene family is one of the most important gene families in plants. It plays important roles in biotic and abiotic stress tolerances, and growth and development. However, little is known about the functional differentiation and relationships among the gene members within a gene family in plants. This study has isolated 563 RLK genes (designated as PgRLK genes) expressed in Jilin ginseng (Panax ginseng C.A. Meyer), investigated their evolution, and deciphered their functional diversification and relationships. The PgRLK gene family is highly diverged and formed into eight types. The LRR type is the earliest and most prevalent, while only the Lec type originated after P. ginseng evolved. Furthermore, although the members of the PgRLK gene family all encode receptor-like protein kinases and share conservative domains, they are functionally very diverse, participating in numerous biological processes. The expressions of different members of the PgRLK gene family are extremely variable within a tissue, at a developmental stage and in the same cultivar, but most of the genes tend to express correlatively, forming a co-expression network. These results not only provide a deeper and comprehensive understanding of the evolution, functional differentiation and correlation of a gene family in plants, but also an RLK genic resource useful for enhanced ginseng genetic improvement.

  17. Differentiating lipedema and Dercum's disease.

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    Beltran, K; Herbst, K L

    2017-02-01

    People with lipedema or Dercum's disease (DD) can have a similar distribution of excess painful nodular subcutaneous adipose tissue (SAT), making them difficult to differentiate. Case series of 94 patients with DD, 160 with lipedema and 18 with both diagnoses (Lip+DD) from a single clinic in an academic medical center to improve identification and differentiation of these disorders by comparison of clinical findings, prevalence of type 2 diabetes (DM2), hypermobility by the Beighton score and assessment of a marker of inflammation, Total complement activity (CH50). Differences between groups were by Student's t-test with α of 0.05. The Lipedema Group had significantly greater weight, body mass index (BMI), gynoid distributed nodular SAT and fibrotic and heavy tissue than the DD Group. Hypermobility was significantly higher in the Lipedema (58±0.5%) than DD Group (23±0.4%; Pfibromyalgia, migraines and lipomas were more prevalent in the DD Group. The percentage of patients with elevated CH50 was significantly positive in both groups. The significantly lower prevalence of DM2 in people with lipedema compared with DD may be due to the greater amount of gynoid fat known to be protective against metabolic disorders. The high percentage of hypermobility in lipedema patients indicates that it may be a comorbid condition. The location of fat, high average daily pain, presence of lipomas and comorbid painful disorders in DD patients may help differentiate from lipedema.

  18. Identification of Transcriptional Modules and Key Genes in Chickens Infected with Salmonella enterica Serovar Pullorum Using Integrated Coexpression Analyses

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    Bao-Hong Liu

    2017-01-01

    Full Text Available Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA and differential coexpression analysis (DCEA to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S. enterica infection. A total of 19 modules from 13,538 genes were associated with the Jak-STAT signaling pathway, the extracellular matrix, cytoskeleton organization, the regulation of the actin cytoskeleton, G-protein coupled receptor activity, Toll-like receptor signaling pathways, and immune system processes; among them, 14 differentially coexpressed modules (DCMs and 2,856 differentially coexpressed genes (DCGs were identified. The global expression of module genes between infected and uninfected chickens showed slight differences but considerable changes for global coexpression. Furthermore, DCGs were consistently linked to the hubs of the modules. These results will help prioritize candidate genes for future studies of Salmonella infection.

  19. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

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    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  20. Degenerative cerebellar diseases and differential diagnoses

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    Reith, W.; Roumia, S.; Dietrich, P.

    2016-01-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [de

  1. [Degenerative cerebellar diseases and differential diagnoses].

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    Reith, W; Roumia, S; Dietrich, P

    2016-11-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions.

  2. A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer's Disease.

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    Liu, Chun-Han; Liu, Lian

    2017-05-08

    BACKGROUND Alzheimer's disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD. MATERIAL AND METHODS We proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected. RESULTS Pathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle. CONCLUSIONS We have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.

  3. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma.

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    Huanwen Wu

    Full Text Available Epidermal growth factor receptor (EGFR is highly expressed in pancreatic ductal adenocarcinoma (PDAC and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.In the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.In total, 64 (48.9% patients expressed EGFR, 68 (51.9% expressed CXCR4, and 33 (25.2% coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938. EGFR expression significantly correlated with tumor differentiation (P = 0.031, whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001. EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026, TNM stage (P = 0.048, and poor tumor differentiation (P = 0.004. By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS and overall survival (OS. Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001 and OS (HR = 2.48, P = 0.001.In conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse

  4. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

    Directory of Open Access Journals (Sweden)

    Anjali Shiras

    2003-11-01

    Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

  5. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Science.gov (United States)

    Faggi, Fiorella; Codenotti, Silvia; Poliani, Pietro Luigi; Cominelli, Manuela; Chiarelli, Nicola; Colombi, Marina; Vezzoli, Marika; Monti, Eugenio; Bono, Federica; Tulipano, Giovanni; Fiorentini, Chiara; Zanola, Alessandra; Lo, Harriet P; Parton, Robert G; Keller, Charles; Fanzani, Alessandro

    2015-01-01

    The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3) in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS), an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC) expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  6. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Directory of Open Access Journals (Sweden)

    Fiorella Faggi

    Full Text Available The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3 in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS, an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  7. Differential diagnosis of Jakob-Creutzfeldt disease.

    Science.gov (United States)

    Paterson, Ross W; Torres-Chae, Charles C; Kuo, Amy L; Ando, Tim; Nguyen, Elizabeth A; Wong, Katherine; DeArmond, Stephen J; Haman, Aissa; Garcia, Paul; Johnson, David Y; Miller, Bruce L; Geschwind, Michael D

    2012-12-01

    To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Retrospective medical record review. A specialty referral center of a tertiary academic medical center. One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis.

  8. Multiscale Embedded Gene Co-expression Network Analysis.

    Directory of Open Access Journals (Sweden)

    Won-Min Song

    2015-11-01

    Full Text Available Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3, the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA by: i introducing quality control of co-expression similarities, ii parallelizing embedded network construction, and iii developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs. We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA. MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  9. Multiscale Embedded Gene Co-expression Network Analysis.

    Science.gov (United States)

    Song, Won-Min; Zhang, Bin

    2015-11-01

    Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

  10. Differential equations with applications in cancer diseases.

    Science.gov (United States)

    Ilea, M; Turnea, M; Rotariu, M

    2013-01-01

    Mathematical modeling is a process by which a real world problem is described by a mathematical formulation. The cancer modeling is a highly challenging problem at the frontier of applied mathematics. A variety of modeling strategies have been developed, each focusing on one or more aspects of cancer. The vast majority of mathematical models in cancer diseases biology are formulated in terms of differential equations. We propose an original mathematical model with small parameter for the interactions between these two cancer cell sub-populations and the mathematical model of a vascular tumor. We work on the assumption that, the quiescent cells' nutrient consumption is long. One the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. MATLAB simulations obtained for transition rate from the quiescent cells' nutrient consumption is long, we show a similar asymptotic behavior for two solutions of the perturbed problem. In this system, the small parameter is an asymptotic variable, different from the independent variable. The graphical output for a mathematical model of a vascular tumor shows the differences in the evolution of the tumor populations of proliferating, quiescent and necrotic cells. The nutrient concentration decreases sharply through the viable rim and tends to a constant level in the core due to the nearly complete necrosis in this region. Many mathematical models can be quantitatively characterized by ordinary differential equations or partial differential equations. The use of MATLAB in this article illustrates the important role of informatics in research in mathematical modeling. The study of avascular tumor growth cells is an exciting and important topic in cancer research and will profit considerably from theoretical input. Interpret these results to be a permanent collaboration between math's and medical oncologists.

  11. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

    Directory of Open Access Journals (Sweden)

    DeYoung Joseph

    2009-08-01

    Full Text Available Abstract Background Amyotrophic Lateral Sclerosis (ALS is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4% showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA was used to find disease-related networks (modules and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls and third dataset (63 patients and 63 controls, thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.

  12. Differentiation of testicular diseases via dynamic MRT

    International Nuclear Information System (INIS)

    Kaiser, W.A.; Reinges, T.; Miersch, W.D.; Vogel, J.

    1994-01-01

    The present study aimed at resolving whether dynamic MRT can improve diagnostic relevance in diseases of the testes compared with conventional spin echo images. The testes of 20 healthy volunteers and of 16 patients of the Department of Urology of the University of Bonn were examined by means of MR tomography. Within 12 hours after MR tomography the patients were surgically explored, biopsied and if necessary orchiectomised. Results obtained with the volunteers were uniform and well reproducible, independent of external influences. On comparing the maximal enhancement curves of the examined various testicular tumors with the standard values established by examining the healthy volunteers, the curves obtained with the malignant testicular tumors were always clearly above the chosen confidence range of 3 standard deviations so that malignancy diagnosis was easy. However, the degree of maximal enhancement did not enable us to arrive at a conclusion in respect of the tumor type or the degree of malignancy. The greatest enhancement occurred with the tumor of Sertoli's cell which could thus be clearly differentiated against the other malignant testicular tumors. Due to masking of the gadolinium effect by haemosiderin deposits, haemorrhagica in the tumor tissue should be excluded by means of T 2 -weighted spin echo sequences before following up a suspicion of malignant testicular tomor. Benign intratesticular changes could be safely separated from malignant findings by means of the maximal enhancement curve lying in the normal range or below the curve of the volunteers. As with other organs, dynamic MR tomography yields definitely more and better information than conventional MR tomography also in the diagnosis of testicular tumours. However, these ''pros'' do not offset the ''cons'' of high costs of such examinations. (orig.) [de

  13. Differential diagnosis of Jakob-Creutzfeldt disease

    OpenAIRE

    Paterson, RW; Torres-Chae, CC; Kuo, AL; Ando, T; Nguyen, EA; Wong, K; DeArmond, SJ; Haman, A; Garcia, P; Johnson, DY; Miller, BL; Geschwind, MD

    2012-01-01

    Objectives: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Design: Retrospective medical record review. Setting: A specialty referral center of a tertiary academic medical center. Participants: One hundred sixty-three serial patients over a 5.5-y...

  14. Differentiating Crohn's disease from intestinal tuberculosis at ...

    African Journals Online (AJOL)

    patients with non-caseating granulomas, as these suggest a very real possibility of ITB. ... There were no significant differences in smoking status, symptom duration or perianal disease. ..... CD, requires a degree of immune competence. This is ...

  15. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oyang Yen-Jen

    2010-10-01

    Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

  16. Trypanosoma cruzi Coexpressing Ornithine Decarboxylase and Green Fluorescence Proteins as a Tool to Study the Role of Polyamines in Chagas Disease Pathology

    Directory of Open Access Journals (Sweden)

    Jeremías José Barclay

    2011-01-01

    Full Text Available Polyamines are essential for Trypanosoma cruzi, the causative agent of Chagas disease. As T. cruzi behaves as a natural auxotrophic organism, it relies on host polyamines biosynthesis. In this paper we obtained a double-transfected T. cruzi parasite that expresses the green fluorescent protein (GFP and a heterologous ornithine decarboxylase (ODC, used itself as a novel selectable marker. These autotrophic and fluorescent parasites were characterized; the ODC presented an apparent Km for ornithine of 0.51 ± 0.16 mM and an estimated Vmax value of 476.2 nmoles/h/mg of protein. These expressing ODC parasites showed higher metacyclogenesis capacity than the auxotrophic counterpart, supporting the idea that polyamines are engaged in this process. This double-transfected T. cruzi parasite results in a powerful tool—easy to follow by its fluorescence—to study the role of polyamines in Chagas disease pathology and in related processes such as parasite survival, invasion, proliferation, metacyclogenesis, and tissue spreading.

  17. [Diseases to differentiate from COPD, with emphasis on bronchial asthma].

    Science.gov (United States)

    Kanazawa, Minoru

    2007-04-01

    Differential diagnosis of chronic obstructive pulmonary disease (COPD) from asthma is not a difficult task for many clinicians. Patients with COPD have a history of heavy smoking and show a slowly progressive dyspnea on exertion and there is little variability in symptoms, and they show a poor response to bronchodilators and corticosteroids. Asthma usually begins in early childhood with atopy, shows episodic dyspnea with wheezing, especially during night and early morning. Some patients, however, show adult onset, irreversible airflow limitation, and neutrophilic airway inflammation. The airway remodeling in asthma may be the cause of confusing pathophysiology. Other diseases showing airway hyperresponsiveness, such as allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, and left heart failure presenting cardiac asthma, may sometimes show similar clinical pictures to COPD. Chronic airway diseases are also possible candidates for differential diagnosis of COPD. Bronchiectasis, sinobronchial syndrome, diffuse panbronchiolitis, obliterative bronchiolitis, and other chronic airway diseases should be considered. Some interstitial lung diseases, such as smoking-related interstitial lung diseases and lymphangioleiomyomatosis, often show obstructive ventilatory impairment, and therefore should be considered in differential diagnosis of COPD.

  18. Inhibition of the Secretory pathway by Foot-and-Mouth disease virus 2BC protein is reproduced by co-expression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C

    DEFF Research Database (Denmark)

    Moffat, Katy; Knox, Caroline; Howell, Gareth

    2007-01-01

    immune responses in vivo. Foot-and-mouth disease virus (FMDV), another picornavirus, can cause persistent infection of ruminants, suggesting it too may inhibit immune responses. Endoplasmic reticulum (ER)-to-Golgi apparatus transport of proteins is blocked by the FMDV 2BC protein. The observation that 2...... blocked in FMDV-infected cells. The block could be reconstituted by coexpression of 2B and 2C, showing that processing of 2BC did not compromise the ability of FMDV to slow secretion. Under these conditions, 2C was located to the Golgi apparatus, and the block in transport also occurred in the Golgi...... apparatus. Interestingly, the block in transport could be redirected to the ER when 2B was coexpressed with a 2C protein fused to an ER retention element. Thus, for FMDV a block in secretion is dependent on both 2B and 2C, with the latter determining the site of the block....

  19. Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Ma, Zihao; Carr, Steven A.; Mertins, Philipp; Zhang, Hui; Zhang, Zhen; Chan, Daniel W.; Ellis, Matthew J. C.; Townsend, R. Reid; Smith, Richard D.; McDermott, Jason E.; Chen, Xian; Paulovich, Amanda G.; Boja, Emily S.; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Rodland, Karin D.; Liebler, Daniel C.; Zhang, Bing

    2016-11-11

    Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

  20. Chronic wasting disease prion infection of differentiated neurospheres.

    Science.gov (United States)

    Iwamaru, Yoshifumi; Mathiason, Candace K; Telling, Glenn C; Hoover, Edward A

    2017-07-04

    A possible strategy to develop more diverse cell culture systems permissive to infection with naturally occurring prions is to exploit culture of neurospheres from transgenic mice expressing the normal prion protein (PrP) of the native host species. Accordingly, we developed differentiated neurosphere cultures from the cervid PrP-expressing mice to investigate whether this in vitro system would support replication of non-adapted cervid-origin chronic wasting disease (CWD) prions. Here we report the successful amplification of disease-associated PrP in differentiated neurosphere cultures within 3 weeks after exposure to CWD prions from both white-tailed deer or elk. This neurosphere culture system provides a new in vitro tool that can be used to assess non-adapted CWD prion propagation and transmission.

  1. Thyroid Ultrasonography in Differentiation between Graves' Disease and Hashimoto's Thyroiditis.

    Science.gov (United States)

    Pishdad, P; Pishdad, G R; Tavanaa, S; Pishdad, R; Jalli, R

    2017-03-01

    Graves' disease and Hashimoto's thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves' disease from Hashimoto's thyroiditis. This study included 149 patients divided into three groups, patients with Graves' disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto's thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves' was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto's group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves' group with 100% and 17.6% specificity and sensitivity, respectively. Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves' disease or Hashimoto's thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed.

  2. Radiological diagnosis in AIDS - associated diseases: survey and differential diagnosis

    International Nuclear Information System (INIS)

    Rademaker, J.; Frahm, C.

    1997-01-01

    Acute manifestations of illnesses in patients with HIV-infection or AIDS will benefit from rapid diagnosis. Radiologic examinations provide substantial information to narrow the differential diagnosis. This article reviews clinically important HIV-associated diseases for the radiologist. The braod spectrum of possible manifestations is illustrated by the accompanying case reports that typify the complexity of diagnoses in this growing problem worldwide. (orig.) [de

  3. Clonal analysis of stem cells in differentiation and disease.

    Science.gov (United States)

    Colom, Bartomeu; Jones, Philip H

    2016-12-01

    Tracking the fate of individual cells and their progeny by clonal analysis has redefined the concept of stem cells and their role in health and disease. The maintenance of cell turnover in adult tissues is achieved by the collective action of populations of stem cells with an equal likelihood of self-renewal or differentiation. Following injury stem cells exhibit striking plasticity, switching from homeostatic behavior in order to repair damaged tissues. The effects of disease states on stem cells are also being uncovered, with new insights into how somatic mutations trigger clonal expansion in early neoplasia. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Differential diagnosis of granulomatous lung disease: clues and pitfalls

    Directory of Open Access Journals (Sweden)

    Shinichiro Ohshimo

    2017-09-01

    Full Text Available Granulomatous lung diseases are a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. Precise clinical evaluation, laboratory testing, pulmonary function testing, radiological imaging including high-resolution computed tomography and often histopathological assessment contribute to make a confident diagnosis of granulomatous lung diseases. Differential diagnosis is challenging, and includes both infectious (mycobacteria and fungi and noninfectious lung diseases (sarcoidosis, necrotising sarcoid granulomatosis, hypersensitivity pneumonitis, hot tub lung, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, rheumatoid nodules, talc granulomatosis, Langerhans cell histiocytosis and bronchocentric granulomatosis. Bronchoalveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial cryobiopsy, positron emission tomography and genetic evaluation are potential candidates to improve the diagnostic accuracy for granulomatous lung diseases. As granuloma alone is a nonspecific histopathological finding, the multidisciplinary approach is important for a confident diagnosis.

  5. Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

    International Nuclear Information System (INIS)

    Storch, A.

    2002-01-01

    Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

  6. CT findings of diffuse pleural diseases: differentiation of malignant disease from tuberculosis

    International Nuclear Information System (INIS)

    Roh, In Gye; Kook, Shin Ho; Lee, Young Rae; Chin, Seung Bum; Park, Yoon Ok; Park, Hae Won

    1997-01-01

    To evaluate whether or not previously known CT criteria for differentiating malignant and benign pleural diseases are useful in the differentiation of diffuse malignant pleural diseases and tuberculosis. We retrospectively analyzed CT scans of 42 patients comprising 20 cases of malignant pleural diseases and 22 cases of tuberculous pleural diseases, according to previously known CT criteria for differentiating malignant and benign pleural diseases. The most common shape of pleural effusion was crescentic in malignant pleural diseases and loculated in tuberculosis. The aggressive nature of pleural effusion, pleural rind, and pleura thickening was 1.5 times more frequently observed in malignant pleural diseases than in tuberculosis. Smooth thickening or smooth nodular pleural thickening and extrapleural deposition of fat were 1.5 times more frequently found in tuberculous than in malignant pleural diseases. Interruption of pleural thickening was found twice as frequently in malignant pleural diseases as in tuberculosis. Decreased lung volume was found twice as frequently in tuberculous as in malignant pleural diseases. Anatomical mediastinal pleural involvement was three times, and irregular nodular pleural thickening nine times more frequent in malignant pleural diseases than in tuberculosis. The sensitivity and specificity of CT findings above 70%, and thus suggesting malignant pleural diseases, were as follows : 1) aggressive nature of pleural fluid collection extending to the azygoesophageal recess or tongue of the lung (51.5%, 75%); 2) involvement of anatomical mediastinal pleura (69.2%, 73.7%); 3) irregular nodular pleural thickening (87.5%, 69%). Although there in overlap between previously known CT criteria for the differentiation of benign and malignant pleural diseases, the aggressive nature of pleural fluid collection extending to the azygoesophageal recess or tongue of the lung, the involvement of anatomical mediastinal pleura and irregular nodular

  7. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma

    Science.gov (United States)

    Na’ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  8. DMPD: Macrophage differentiation and function in health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available in health and disease. PubmedID 18251777 Title Macrophage differentiation and function in health and disease...thol Int. 2008 Mar;58(3):143-55. (.png) (.svg) (.html) (.csml) Show Macrophage differentiation and function

  9. Degenerative cerebellar diseases and differential diagnoses; Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W.; Roumia, S.; Dietrich, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-11-15

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [German] Klinisch imponieren Kleinhirnsyndrome durch Ataxie, Dysarthrie, Dysmetrie, Intentionstremor und Augenbewegungsstoerungen. Neben der Anamnese und klinischen Untersuchung ist die Bildgebung v. a. wichtig um andere Erkrankungen wie Hydrozephalus und Multiinfarktdemenz von degenerativen Kleinhirnerkrankungen zu differenzieren. Zu den degenerativen Erkrankungen mit Kleinhirnbeteiligung gehoeren der Morbus Parkinson, die Multisystematrophie sowie weitere Erkrankungen einschliesslich der spinozerebellaeren Ataxien. Neben der MRT sind auch nuklearmedizinische Untersuchungen zur Differenzierung hilfreich. Axiale Fluid-attenuated-inversion-recovery(FLAIR)- und T2-gewichtete Sequenzen koennen mitunter eine Signalsteigerung im Pons als Ausdruck einer Degeneration der pontinen Neuronen und transversalen Bahnen im Brueckenfuss zeigen. Die Bildgebung ist aber v. a. notwendig, um andere Erkrankungen wie Normaldruckhydrozephalus

  10. Creutzfeldt-Jakob disease: a case report and differential diagnoses.

    Science.gov (United States)

    Kojima, Gotaro; Tatsuno, Brent K; Inaba, Michiko; Velligas, Stephanie; Masaki, Kamal; Liow, Kore K

    2013-04-01

    Sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disorder of unknown etiology that causes rapidly progressive dementia. This disease is uniformly fatal and most patients die within 12 months. Clinical findings include myoclonus, visual disturbances, and cerebellar and pyramidal/extrapyramidal signs in addition to rapidly progressive cognitive and functional impairment. These findings are all non-specific and it is often difficult and challenging to diagnose premortem because of low awareness and clinical suspicion. We present a 66-year-old woman with a 5-month history of rapidly progressive dementia. After a series of extensive diagnostic examinations and continuous follow-up, she was diagnosed with probable sporadic Creutzfeldt-Jakob disease based on Centers for Disease Control and Prevention (CDC) criteria, with key findings of rapidly progressive dementia, blurry vision, extrapyramidal signs (cogwheel rigidity), and abnormal hyperintensity signals on diffusion-weighted MRI. Her symptoms progressively worsened and she died 7 months after the onset. The postmortem brain autopsy demonstrated the presence of abnormal protease-resistant prion protein by Western Blot analysis. A literature review was performed on differential diagnoses that present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease. These include Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, meningoencephalitis, corticobasal degeneration, progressive supranuclear palsy, CADASIL, and paraneoplastic encephalomyelitis.

  11. Lymphogranuloma venereum proctitis: a differential diagnose to inflammatory bowel disease.

    Science.gov (United States)

    Høie, Sverre; Knudsen, Lene Surland; Gerstoft, Jan

    2011-04-01

    Lymphogranuloma venereum (LGV) is a sexually transmitted disease, endemic in tropical and subtropical areas for many years. After 2003 there have been several outbreaks in western countries, especially among HIV-positive men who have sex with men (MSM). An important manifestation of LGV is a proctitis, with a clinical presentation and endoscopic findings resembling those of inflammatory bowel diseases (IBDs). LGV is considered new in Scandinavia. This case report focuses on difficulties in differentiating LGV and IBD. This case report used a systematic search in the literature using PubMed and clinical cases from the Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark (Cases 1-3) and the Section of Surgery, Hamar Hospital, Norway (Case 4). Clinical and endoscopic findings in LGV and IBD resemble each other. All cases were MSM. Three out of four were HIV-positive. Three out of four contacted their general practitioner (GP) due to gastrointestinal (GI) symptoms, and were referred to a gastroenterologist (GE) with suspicion of IBD. Because of non-successful IBD treatment, control of HIV status, relapses of GI-symptoms or extended information concerning sexual habits, LGV was suspected and diagnosed. All patients responded with remission of GI-symptoms and endoscopic findings after oral treatment with doxycycline. Due to similarities between LGV and IBD, LGV should be considered as a differential diagnosis in patients with proctitis or IBD-related symptoms, especially among HIV-positive men. Hence LGV patients may be spared long-lasting examination, mistreatment and surgery.

  12. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

    Directory of Open Access Journals (Sweden)

    Alison M Anderson

    Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

  13. [Differentiation therapy for non-acidic gastroesophageal reflux disease].

    Science.gov (United States)

    Lishchuk, N B; Simanenkov, V I; Tikhonov, S V

    2017-01-01

    To investigate the clinical and pathogenetic features of the non-acidic types of gastroesophageal reflux disease (GERD) and to evaluate the impact of combined therapy versus monotherapy on the course of this disease. The investigation enrolled 62 patients with non-acidic GERD. The follow-up period was 6 weeks. The patients were divided into 2 groups: 1) weakly acidic gastroesophageal refluxes (GER); 2) weakly alkaline GER. Then each group was distributed, thus making up 4 groups: 1) 19 patients with weakly acidic GER who received monotherapy with rabeprazole 20 mg/day; 2) 21 patients with weakly acidic GER had combined therapy with rabeprazole 20 mg and itopride; 3) 8 patients with weakly alkaline GER who received ursodeoxycholic acid (UDCA) monotherapy; and 4) 14 patients with weakly alkaline GER who had combined therapy with UDCA and itopride, The clinical symptoms of the disease, the endoscopic pattern of the upper gastrointestinal tract (GIT) mucosa, histological changes in the esophageal and gastric mucosa, and the results of 24-hour impedance pH monitoring were assessed over time. During differentiation therapy, the majority of patients reported positive clinical changes and an improved or unchanged endoscopic pattern. Assessment of impedance pH monitoring results revealed decreases in the overall number of GERs, the presence of a bolus in the esophagus, and the number of proximal refluxes. These changes were noted not only in patients taking proton pump inhibitors (PPIs), but also in those treated with UDCA monotherapy or combined PPI and prokinetic therapy. A differentiated approach to non-acidic GER treatment contributes to its efficiency. Adding the prokinetic itomed (itopride hydrochloride) to PPI therapy in a patient with weakly acidic GER enhances the efficiency of treatment, by positively affecting upper GIT motility. The mainstay of therapy for GERD with a predominance of weakly alkaline refluxes is UDCA, the combination of the latter and the

  14. Novel Approach for Coexpression Analysis of E2F1–3 and MYC Target Genes in Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Fengfeng Wang

    2014-01-01

    Full Text Available Background. Chronic myelogenous leukemia (CML is characterized by tremendous amount of immature myeloid cells in the blood circulation. E2F1–3 and MYC are important transcription factors that form positive feedback loops by reciprocal regulation in their own transcription processes. Since genes regulated by E2F1–3 or MYC are related to cell proliferation and apoptosis, we wonder if there exists difference in the coexpression patterns of genes regulated concurrently by E2F1–3 and MYC between the normal and the CML states. Results. We proposed a method to explore the difference in the coexpression patterns of those candidate target genes between the normal and the CML groups. A disease-specific cutoff point for coexpression levels that classified the coexpressed gene pairs into strong and weak coexpression classes was identified. Our developed method effectively identified the coexpression pattern differences from the overall structure. Moreover, we found that genes related to the cell adhesion and angiogenesis properties were more likely to be coexpressed in the normal group when compared to the CML group. Conclusion. Our findings may be helpful in exploring the underlying mechanisms of CML and provide useful information in cancer treatment.

  15. Lymphogranuloma venereum proctitis: A differential diagnose to inflammatory bowel disease

    DEFF Research Database (Denmark)

    Høie, Sverre; Knudsen, Lene Surland; Gerstoft, Jan

    2011-01-01

    each other. All cases were MSM. Three out of four were HIV-positive. Three out of four contacted their general practitioner (GP) due to gastrointestinal (GI) symptoms, and were referred to a gastroenterologist (GE) with suspicion of IBD. Because of non-successful IBD treatment, control of HIV status...... as a differential diagnosis in patients with proctitis or IBD-related symptoms, especially among HIV-positive men. Hence LGV patients may be spared long-lasting examination, mistreatment and surgery.......Abstract Objective. Lymphogranuloma venereum (LGV) is a sexually transmitted disease, endemic in tropical and subtropical areas for many years. After 2003 there have been several outbreaks in western countries, especially among HIV-positive men who have sex with men (MSM). An important...

  16. [Weighted gene co-expression network analysis in biomedicine research].

    Science.gov (United States)

    Liu, Wei; Li, Li; Ye, Hua; Tu, Wei

    2017-11-25

    High-throughput biological technologies are now widely applied in biology and medicine, allowing scientists to monitor thousands of parameters simultaneously in a specific sample. However, it is still an enormous challenge to mine useful information from high-throughput data. The emergence of network biology provides deeper insights into complex bio-system and reveals the modularity in tissue/cellular networks. Correlation networks are increasingly used in bioinformatics applications. Weighted gene co-expression network analysis (WGCNA) tool can detect clusters of highly correlated genes. Therefore, we systematically reviewed the application of WGCNA in the study of disease diagnosis, pathogenesis and other related fields. First, we introduced principle, workflow, advantages and disadvantages of WGCNA. Second, we presented the application of WGCNA in disease, physiology, drug, evolution and genome annotation. Then, we indicated the application of WGCNA in newly developed high-throughput methods. We hope this review will help to promote the application of WGCNA in biomedicine research.

  17. Genetic biomarkers for brain hemisphere differentiation in Parkinson's Disease

    Science.gov (United States)

    Hourani, Mou'ath; Mendes, Alexandre; Berretta, Regina; Moscato, Pablo

    2007-11-01

    This work presents a study on the genetic profile of the left and right hemispheres of the brain of a mouse model of Parkinson's disease (PD). The goal is to characterize, in a genetic basis, PD as a disease that affects these two brain regions in different ways. Using the same whole-genome microarray expression data introduced by Brown et al. (2002) [1], we could find significant differences in the expression of some key genes, well-known to be involved in the mechanisms of dopamine production control and PD. The problem of selecting such genes was modeled as the MIN (α,β)—FEATURE SET problem [2]; a similar approach to that employed previously to find biomarkers for different types of cancer using gene expression microarray data [3]. The Feature Selection method produced a series of genetic signatures for PD, with distinct expression profiles in the Parkinson's model and control mice experiments. In addition, a close examination of the genes composing those signatures shows that many of them belong to genetic pathways or have ontology annotations considered to be involved in the onset and development of PD. Such elements could provide new clues on which mechanisms are implicated in hemisphere differentiation in PD.

  18. Infectious diseases of the brain: imaging and differential diagnosis; Infektioese Hirnerkrankungen: Bildgebung und differenzialdiagnostische Aspekte

    Energy Technology Data Exchange (ETDEWEB)

    Haehnel, S.; Seitz, A. [Abt. Neuroradiologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany); Storch-Hagenlocher, B. [Abt. Neurologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany)

    2006-09-15

    Infectious diseases of the central nervous system have to be considered in differential diagnosis particularly in immunocompromised persons. Neuro-imaging, specifically advanced techniques such as diffusion weighted MRI and perfusion MRI contribute much to the differentiation of brain infections and for differentiating brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria of the most important brains infections in adults and in pediatric patients and discuss differential diagnostic aspects in detail. (orig.)

  19. Patterns of population differentiation of candidate genes for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ding Keyue

    2007-07-01

    Full Text Available Abstract Background The basis for ethnic differences in cardiovascular disease (CVD susceptibility is not fully understood. We investigated patterns of population differentiation (FST of a set of genes in etiologic pathways of CVD among 3 ethnic groups: Yoruba in Nigeria (YRI, Utah residents with European ancestry (CEU, and Han Chinese (CHB + Japanese (JPT. We identified 37 pathways implicated in CVD based on the PANTHER classification and 416 genes in these pathways were further studied; these genes belonged to 6 biological processes (apoptosis, blood circulation and gas exchange, blood clotting, homeostasis, immune response, and lipoprotein metabolism. Genotype data were obtained from the HapMap database. Results We calculated FST for 15,559 common SNPs (minor allele frequency ≥ 0.10 in at least one population in genes that co-segregated among the populations, as well as an average-weighted FST for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions or non-functional (intronic and synonymous sites. Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants. A significant variation in FST was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high FST. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST values was noted among pairwise population comparisons for different biological processes. Conclusion These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.

  20. Predicting targeted drug combinations based on Pareto optimal patterns of coexpression network connectivity.

    Science.gov (United States)

    Penrod, Nadia M; Greene, Casey S; Moore, Jason H

    2014-01-01

    Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced tumor adaptation. We use this approach to identify tumor-essential genes as druggable candidates. We apply our method to a set of ER(+) breast tumor samples, collected before (n = 58) and after (n = 60) neoadjuvant treatment with the aromatase inhibitor letrozole, to prioritize genes as targets for combination therapy with letrozole treatment. We validate letrozole-induced tumor adaptation through coexpression and pathway analyses in an independent data set (n = 18). We find pervasive differential coexpression between the untreated and letrozole-treated tumor samples as evidence of letrozole-induced tumor adaptation. Based on patterns of coexpression, we identify ten genes as potential candidates for combination therapy with letrozole including EPCAM, a letrozole-induced essential gene and a target to which drugs have already been developed as cancer therapeutics. Through replication, we validate six letrozole-induced coexpression relationships and confirm the epithelial-to-mesenchymal transition as a process that is upregulated in the residual tumor samples following letrozole treatment. To derive the greatest benefit from molecularly targeted drugs it is critical to design combination

  1. Network-based identification of biomarkers coexpressed with multiple pathways.

    Science.gov (United States)

    Guo, Nancy Lan; Wan, Ying-Wooi

    2014-01-01

    Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication. Specifically, we evaluated implication networks, Boolean networks, Bayesian networks, and Pearson's correlation networks in constructing gene coexpression networks for identifying lung cancer diagnostic and prognostic biomarkers. The results show that implication networks, implemented in Genet package, identified sets of biomarkers that generated an accurate prediction of lung cancer risk and metastases; meanwhile, implication networks revealed more biologically relevant molecular interactions than Boolean networks, Bayesian networks, and Pearson's correlation networks when evaluated with MSigDB database.

  2. Studying the Complex Expression Dependences between Sets of Coexpressed Genes

    Directory of Open Access Journals (Sweden)

    Mario Huerta

    2014-01-01

    Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

  3. EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

    Science.gov (United States)

    Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

    2014-06-01

    Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

  4. Infectious diseases of brain parenchyma in adults: imaging and differential diagnosis

    International Nuclear Information System (INIS)

    Haehnel, S.; Kress, B.; Stippich, C.; Sartor, K.; Seitz, A.; Storch-Hagenlocher, B.; Forsting, M.; Jansen, O.

    2005-01-01

    Infectious diseases of the central nervous system have often to be considered in differential diagnosis, particularly in immunocompromised persons. Neuroimaging, specifically advanced techniques such as diffusion-weighted MRI and perfusion MRI contribute much to the differentiation of various brain infections and to delineation of brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria for the most important brain infections in adults and discuss in detail differential diagnostic aspects. (orig.)

  5. Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Podlesniy, Petar; Llorens, Franc; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel; Zerr, Inga; Trullas, Ramon

    2016-05-01

    Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown. CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia. Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t-tau, p-tau, and 14-3-3 protein levels in CSF. Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD. Copyright © 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  6. Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Borlawsky Tara B

    2010-10-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. Results In this paper, we investigate the use of gene co-expression network analysis to identify potential biomarkers for CLL. Specifically we focused on the co-expression network involving ZAP70, a well characterized biomarker for CLL. We selected 23 microarray datasets corresponding to multiple types of cancer from the Gene Expression Omnibus (GEO and used the frequent network mining algorithm CODENSE to identify highly connected gene co-expression networks spanning the entire genome, then evaluated the genes in the co-expression network in which ZAP70 is involved. We then applied a set of feature selection methods to further select genes which are capable of predicting IgVH mutation status from the ZAP70 co-expression network. Conclusions We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

  7. Myeloid differentiation factor 88-deficient bone marrow cells improve Alzheimer's disease-related symptoms and pathology

    NARCIS (Netherlands)

    Hao, W.; Liu, Y.; Liu, S.; Walter, S.; Grimm, M.O.; Kiliaan, A.J.; Penke, B.; Hartmann, T.; Rube, C.E.; Menger, M.D.; Fassbender, K.

    2011-01-01

    Alzheimer's disease is characterized by extracellular deposits of amyloid beta peptide in the brain. Increasing evidence suggests that amyloid beta peptide injures neurons both directly and indirectly by triggering neurotoxic innate immune responses. Myeloid differentiation factor 88 is the key

  8. Serum Fragments of Tau for the Differential Diagnosis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Inekci, Dilek; Henriksen, K.; Linemann, T.

    2015-01-01

    Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate...

  9. Characterization of Verticillium dahliae disease reactions in lettuce differential cultivars

    Science.gov (United States)

    Soilborne diseases significantly affect high value crops in coastal California, including lettuce and strawberry. Breeding crops for pathogen resistance is a strategy for the sustainable management of crop disease. Verticillium dahliae is a soilborne fungus that causes wilt and economic losses in a ...

  10. On the Problem of Differential Diagnosis of Inflammatory and Functional Bowel Diseases

    Directory of Open Access Journals (Sweden)

    I.Ya. Budzak

    2013-04-01

    Full Text Available The paper describes the problems of differential diagnosis of inflammatory (ulcerative colitis, Crohn’s disease and functional (irritable bowel syndrome disease of the intestine. The necessity of such differential diagnosis in certain categories of patients was noted. The possibilities of instrumental and laboratory methods of study are shown. Particular attention is paid to the definition of fecal tests — calprotectin and lactoferrin. An analysis of the studies of their information content has been carried out.

  11. Differential diagnosis of neurodegenerative diseases using structural MRI data

    DEFF Research Database (Denmark)

    Koikkalainen, Juha; Rhodius-Meester, Hanneke; Tolonen, Antti

    2016-01-01

    individuals was used for evaluation. The cross-validated classification accuracy was 70.6% and balanced accuracy was 69.1% for the five disease groups using only automatically determined MRI features. Vascular dementia patients could be detected with high sensitivity (96%) using features from FLAIR images....... Controls (sensitivity 82%) and Alzheimer's disease patients (sensitivity 74%) could be accurately classified using T1-based features, whereas the most difficult group was the dementia with Lewy bodies (sensitivity 32%). These results were notable better than the classification accuracies obtained...... characteristics from T1 images, and vascular characteristics from FLAIR images. Classification was performed using a multi-class classifier based on Disease State Index methodology. The classifier provided continuous probability indices for each disease to support clinical decision making. A dataset of 504...

  12. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    International Nuclear Information System (INIS)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail; Topalkara, Kamil; Erkoc, Mustafa F.

    2015-01-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm 2 . ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm 2 which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10 -3 mm 2 /s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10 -3 mm 2 /s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10 -3 mm 2 /s in MS patients, and (0.75 ± 0.08) x 10 -3 mm 2 /s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  13. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    Energy Technology Data Exchange (ETDEWEB)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey); Topalkara, Kamil [Bayindir Hospital, Department of Neurology, Ankara (Turkey); Erkoc, Mustafa F. [Bozok University School of Medicine, Department of Radiology, Yozgat (Turkey)

    2015-04-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm{sup 2}. ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm{sup 2} which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10{sup -3} mm{sup 2}/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10{sup -3} mm{sup 2}/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10{sup -3} mm{sup 2}/s in MS patients, and (0.75 ± 0.08) x 10{sup -3} mm{sup 2}/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  14. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

    2017-02-01

    To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

  15. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Cirera Salicio, Susanna; Zhernakova, Daria V.

    2014-01-01

    interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model...... (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P ... the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using...

  16. Differential overexpression of SERPINA3 in human prion diseases.

    Science.gov (United States)

    Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

    2017-11-15

    Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

  17. Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Zhifen Liu

    Full Text Available LncRNAs, which represent one of the most highly expressed classes of ncRNAs in the brain, are becoming increasingly interesting with regard to brain functions and disorders. However, changes in the expression of regulatory lncRNAs in Major Depressive Disorder (MDD have not yet been reported. Using microarrays, we profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood sampled from MDD patients as well as demographically-matched controls. Among these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed, 17 of which were documented as depression-related gene in previous studies. Gene Ontology (GO and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to fundamental metabolic processes and neurodevelopment diseases. To investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we also constructed co-expression networks composed of the lncRNAs and mRNAs, which shows significant correlated patterns of expression. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of mRNAs as they have previously been reported associations with MDD. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in MDD using microarray technology. We identified circulating lncRNAs that are aberrantly expressed in MDD and the results suggest that lncRNAs may contribute to the molecular pathogenesis of MDD.

  18. Co-expression of putative stemness and epithelial-to-mesenchymal transition markers on single circulating tumour cells from patients with early and metastatic breast cancer.

    Science.gov (United States)

    Papadaki, Maria A; Kallergi, Galatea; Zafeiriou, Zafeiris; Manouras, Lefteris; Theodoropoulos, Panayiotis A; Mavroudis, Dimitris; Georgoulias, Vassilis; Agelaki, Sofia

    2014-09-03

    The detection of circulating tumor cells (CTCs) in peripheral blood (PB) of patients with breast cancer predicts poor clinical outcome. Cancer cells with stemness and epithelial-to-mesenchymal transition (EMT) features display enhanced malignant and metastatic potential. A new methodology was developed in order to investigate the co-expression of a stemness and an EMT marker (ALDH1 and TWIST, respectively) on single CTCs of patients with early and metastatic breast cancer. Triple immunofluorescence using anti-pancytokeratin (A45-B/B3), anti-ALDH1 and anti-TWIST antibodies was performed in cytospins prepared from hepatocellular carcinoma HepG2 cells and SKBR-3, MCF-7 and MDA.MB.231 breast cancer cell lines. Evaluation of ALDH1 expression levels (high, low or absent) and TWIST subcellular localization (nuclear, cytoplasmic or absent) was performed using the ARIOL system. Cytospins prepared from peripheral blood of patients with early (n = 80) and metastatic (n = 50) breast cancer were analyzed for CTC detection (based on pan-cytokeratin expression and cytomorphological criteria) and characterized according to ALDH1 and TWIST. CTCs were detected in 13 (16%) and 25 (50%) patients with early and metastatic disease, respectively. High ALDH1 expression (ALDH1high) and nuclear TWIST localization (TWISTnuc) on CTCs was confirmed in more patients with metastatic than early breast cancer (80% vs. 30.8%, respectively; p = 0.009). In early disease, ALDH1low/neg CTCs (p = 0.006) and TWISTcyt/neg CTCs (p = 0.040) were mainly observed. Regarding co-expression of these markers, ALDH1high/TWISTnuc CTCs were more frequently evident in the metastatic setting (76% vs. 15.4% of patients, p = 0.001; 61.5% vs. 12.9% of total CTCs), whereas in early disease ALDH1low/neg/TWISTcyt/neg CTCs were mainly detected (61.5% vs. 20% of patients, p = 0.078; 41.9% vs. 7.7% of total CTCs). A new assay is provided for the evaluation of ALDH1 and TWIST co-expression at the

  19. Lymphogranuloma venereum proctitis: A differential diagnose to inflammatory bowel disease

    DEFF Research Database (Denmark)

    Høie, Sverre; Knudsen, Lene Surland; Gerstoft, Jan

    2011-01-01

    Abstract Objective. Lymphogranuloma venereum (LGV) is a sexually transmitted disease, endemic in tropical and subtropical areas for many years. After 2003 there have been several outbreaks in western countries, especially among HIV-positive men who have sex with men (MSM). An important...

  20. Osteomesopyknosis associated to renal lithiasis. Case report. Differential diagnosis of the axial osteoesclerosant diseases

    International Nuclear Information System (INIS)

    Quintana, Gerardo; Fernandez, Andres; Restrepo, Jose Felix; Rojas, Adriana; Calvo, Enrique; Rondon, Federico; Sanchez, Alvaro; Forero, Elias; Iglesias, Antonio

    2004-01-01

    In this article we present a brief description of the bone diseases characterized by osteosclerosis. We present our experience with their morpho-radiological changes, we describe a case of osteomesopyknosis associated to renal lithiasis and we propose a classification for osteosclerosant diseases of the axial skeleton with practical differential diagnosis of these conditions

  1. Differential replication of foot-and-mouth disease viruses in mice determine lethality

    Science.gov (United States)

    Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

  2. Differential diagnosis of genetic disease by DNA restriction fragment length polymorphisms

    NARCIS (Netherlands)

    Bolhuis, P. A.; Defesche, J. C.; van der Helm, H. J.

    1987-01-01

    DNA restriction fragment length polymorphisms (RFLPs) are used for diagnosis of genetic disease in families known to be affected by specific disorders, but RFLPs can be also useful for the differential diagnosis of hereditary disease. An RFLP pattern represents the inheritance of chromosomal markers

  3. Characterization of chemically induced liver injuries using gene co-expression modules.

    Directory of Open Access Journals (Sweden)

    Gregory J Tawa

    Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

  4. Complex and differential glial responses in Alzheimer's disease and ageing.

    Science.gov (United States)

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  5. Functional Module Analysis for Gene Coexpression Networks with Network Integration.

    Science.gov (United States)

    Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

    2015-01-01

    Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

  6. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

    Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  7. Protein Coexpression Using FMDV 2A: Effect of “Linker” Residues

    Directory of Open Access Journals (Sweden)

    Ekaterina Minskaia

    2013-01-01

    Full Text Available Many biomedical applications absolutely require, or are substantially enhanced by, coexpression of multiple proteins from a single vector. Foot-and-mouth disease virus 2A (F2A and “2A-like” sequences (e.g., Thosea asigna virus 2A; T2A are used widely for this purpose since multiple proteins can be coexpressed by linking open reading frames (ORFs to form a single cistron. The activity of F2A “cleavage” may, however, be compromised by both the use of shorter versions of F2A and the sequences (derived from multiple-purpose cloning sites used to link F2A to the upstream protein. To characterise these effects, different lengths of F2A and T2A were inserted between green and cherry fluorescent proteins. Mutations were introduced in the linker region immediately upstream of both F2A- and T2A-based constructs and activities determined using both cell-free translation systems and transfected cells. In shorter versions of F2A, activity may be affected by both the C-terminal sequence of the protein upstream and, equally strikingly, the residues immediately upstream introduced during cloning. Mutations significantly improved activity for shorter versions of F2A but could decrease activity in the case of T2A. These data will aid the design of cloning strategies for the co-expression of multiple proteins in biomedical/biotechnological applications.

  8. Recombinant amyloid beta-peptide production by coexpression with an affibody ligand

    Directory of Open Access Journals (Sweden)

    Dobson Christopher M

    2008-10-01

    Full Text Available Abstract Background Oligomeric and fibrillar aggregates of the amyloid β-peptide (Aβ have been implicated in the pathogenesis of Alzheimer's disease (AD. The characterization of Aβ assemblies is essential for the elucidation of the mechanisms of Aβ neurotoxicity, but requires large quantities of pure peptide. Here we describe a novel approach to the recombinant production of Aβ. The method is based on the coexpression of the affibody protein ZAβ3, a selected affinity ligand derived from the Z domain three-helix bundle scaffold. ZAβ3 binds to the amyloidogenic central and C-terminal part of Aβ with nanomolar affinity and consequently inhibits aggregation. Results Coexpression of ZAβ3 affords the overexpression of both major Aβ isoforms, Aβ(1–40 and Aβ(1–42, yielding 4 or 3 mg, respectively, of pure 15N-labeled peptide per liter of culture. The method does not rely on a protein-fusion or -tag and thus does not require a cleavage reaction. The purified peptides were characterized by NMR, circular dichroism, SDS-PAGE and size exclusion chromatography, and their aggregation propensities were assessed by thioflavin T fluorescence and electron microscopy. The data coincide with those reported previously for monomeric, largely unstructured Aβ. ZAβ3 coexpression moreover permits the recombinant production of Aβ(1–42 carrying the Arctic (E22G mutation, which causes early onset familial AD. Aβ(1–42E22G is obtained in predominantly monomeric form and suitable, e.g., for NMR studies. Conclusion The coexpression of an engineered aggregation-inhibiting binding protein offers a novel route to the recombinant production of amyloidogenic Aβ peptides that can be advantageously employed to study the molecular basis of AD. The presented expression system is the first for which expression and purification of the aggregation-prone Arctic variant (E22G of Aβ(1–42 is reported.

  9. Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

    Science.gov (United States)

    Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

    2018-01-01

    Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Recombinant amyloid beta-peptide production by coexpression with an affibody ligand

    Science.gov (United States)

    Macao, Bertil; Hoyer, Wolfgang; Sandberg, Anders; Brorsson, Ann-Christin; Dobson, Christopher M; Härd, Torleif

    2008-01-01

    Background Oligomeric and fibrillar aggregates of the amyloid β-peptide (Aβ) have been implicated in the pathogenesis of Alzheimer's disease (AD). The characterization of Aβ assemblies is essential for the elucidation of the mechanisms of Aβ neurotoxicity, but requires large quantities of pure peptide. Here we describe a novel approach to the recombinant production of Aβ. The method is based on the coexpression of the affibody protein ZAβ3, a selected affinity ligand derived from the Z domain three-helix bundle scaffold. ZAβ3 binds to the amyloidogenic central and C-terminal part of Aβ with nanomolar affinity and consequently inhibits aggregation. Results Coexpression of ZAβ3 affords the overexpression of both major Aβ isoforms, Aβ(1–40) and Aβ(1–42), yielding 4 or 3 mg, respectively, of pure 15N-labeled peptide per liter of culture. The method does not rely on a protein-fusion or -tag and thus does not require a cleavage reaction. The purified peptides were characterized by NMR, circular dichroism, SDS-PAGE and size exclusion chromatography, and their aggregation propensities were assessed by thioflavin T fluorescence and electron microscopy. The data coincide with those reported previously for monomeric, largely unstructured Aβ. ZAβ3 coexpression moreover permits the recombinant production of Aβ(1–42) carrying the Arctic (E22G) mutation, which causes early onset familial AD. Aβ(1–42)E22G is obtained in predominantly monomeric form and suitable, e.g., for NMR studies. Conclusion The coexpression of an engineered aggregation-inhibiting binding protein offers a novel route to the recombinant production of amyloidogenic Aβ peptides that can be advantageously employed to study the molecular basis of AD. The presented expression system is the first for which expression and purification of the aggregation-prone Arctic variant (E22G) of Aβ(1–42) is reported. PMID:18973685

  11. Identification of PEG-induced water stress responsive transcripts using co-expression network in Eucalyptus grandis.

    Science.gov (United States)

    Ghosh Dasgupta, Modhumita; Dharanishanthi, Veeramuthu

    2017-09-05

    Ecophysiological studies in Eucalyptus have shown that water is the principal factor limiting stem growth. Effect of water deficit conditions on physiological and biochemical parameters has been extensively reported in Eucalyptus. The present study was conducted to identify major polyethylene glycol induced water stress responsive transcripts in Eucalyptus grandis using gene co-expression network. A customized array representing 3359 water stress responsive genes was designed to document their expression in leaves of E. grandis cuttings subjected to -0.225MPa of PEG treatment. The differentially expressed transcripts were documented and significantly co-expressed transcripts were used for construction of network. The co-expression network was constructed with 915 nodes and 3454 edges with degree ranging from 2 to 45. Ninety four GO categories and 117 functional pathways were identified in the network. MCODE analysis generated 27 modules and module 6 with 479 nodes and 1005 edges was identified as the biologically relevant network. The major water responsive transcripts represented in the module included dehydrin, osmotin, LEA protein, expansin, arabinogalactans, heat shock proteins, major facilitator proteins, ARM repeat proteins, raffinose synthase, tonoplast intrinsic protein and transcription factors like DREB2A, ARF9, AGL24, UNE12, WLIM1 and MYB66, MYB70, MYB 55, MYB 16 and MYB 103. The coordinated analysis of gene expression patterns and coexpression networks developed in this study identified an array of transcripts that may regulate PEG induced water stress responses in E. grandis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Differential patterns of histone acetylation in inflammatory bowel diseases

    Directory of Open Access Journals (Sweden)

    Adcock Ian M

    2011-01-01

    Full Text Available Abstract Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD to study the expression of acetylated histones (H 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP in dextran sulfate sodium (DSS-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

  13. Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

    Science.gov (United States)

    Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

    2017-10-01

    The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    International Nuclear Information System (INIS)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-01-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns. (orig.) [de

  15. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-12-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns.

  16. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases

    OpenAIRE

    Oliveira,Marcio Sacramento de; Leon,Antônio Ponce de; Mattos,Inês Echenique; Koifman,Sérgio

    2011-01-01

    This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99), PM10, SO2, and O3 levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths f...

  17. Differentiation of diffuse liver disease with computer-aided tissue echo quantification

    International Nuclear Information System (INIS)

    Cha, Joo Hee; Choi, Byung Ihm; Yun, Eun Joo; Ko, Young Hwan; Song, Chi Sung; Kim, Seung Hyup; Han, Joon Koo; Kim, Tae Kyoung; Lee, Dong Hyuk; Kim, Jong Hyo

    1999-01-01

    The purpose of this study was to evaluate the efficacy of computer-aided tissue echo quantification technique in the differentiation of diffuse liver diseases. Sixty-five patients with chronic liver disease including chronic hepatitis in 21 patients, fatty liver in 11, and liver cirrhosis in 33, and 55 normal volunteers were included in this study. The sonographic images by the Sono-PACS(MARO, Seoul) was recalled and the analysis was done for the hepatic parenchymal coarseness by the program using Visual C++. Difference histogram variation (DHV), edge density (ED) and intertia of concurrence matrix (ICM) were used as the coarseness index. These three indexes were statistically significant (p<0.05) in the differentiation of these four groups. The accuracy of the differentiation between any two of four groups was 83.0%. The accuracy of the differentiation of these four groups was 70.8% at the same time. The computer-aided tissue echo quantification technique is a complementary study for the differentiation of diffuse liver disease.

  18. Network analysis of differential expression for the identification of disease-causing genes.

    Directory of Open Access Journals (Sweden)

    Daniela Nitsch

    Full Text Available Genetic studies (in particular linkage and association studies identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved. We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes.

  19. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon

    Directory of Open Access Journals (Sweden)

    Po-Chang Wu

    2013-08-01

    Conclusion: The nailfold capillaroscopic (NC patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity.

  20. Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

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    Stefano Zanigni

    2016-01-01

    Conclusion: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

  1. Random forest to differentiate dementia with Lewy bodies from Alzheimer's disease

    NARCIS (Netherlands)

    Dauwan, Meenakshi; van der Zande, Jessica J.; van Dellen, Edwin; Sommer, Iris E C; Scheltens, Philip; Lemstra, Afina W.; Stam, Cornelis J.

    2016-01-01

    Introduction The aim of this study was to build a random forest classifier to improve the diagnostic accuracy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and to quantify the relevance of multimodal diagnostic measures, with a focus on electroencephalography

  2. Differential Diagnosis of Gynecologic Organ-Related Diseases in Women Presenting with Ascites

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    Ming-Huei Cheng

    2008-12-01

    Full Text Available Ascites is a pathologic accumulation of fluid within the peritoneal cavity, and usually develops as a result of liver disease, congestive heart failure or nephrotic syndrome. Ascites is also a common manifestation of some gynecologic diseases. It is important that health care workers consider gynecologic problems among the potential differential diagnoses in patients presenting with ascites. Various kinds of ovarian diseases, such as epithelial ovarian cancer, benign ovarian fibroma, stromal hyperplasia, ovarian hyperstimulation syndrome, primary peritoneal serous carcinoma, endometriosis and peritoneal tuberculosis, should be kept in mind when women are found to have ascites.

  3. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  4. How to differentiate non-erosive reflux disease from functional heartburn.

    Science.gov (United States)

    Ke, Mei Yun

    2012-12-01

    Heartburn is a common symptom in gastroesophageal reflux disease. Endoscopic examination can differentiate between reflux esophagitis and non-erosive reflux disease (NERD), but not between NERD and functional heartburn. With the development of new techniques, more NERD patients could be identified among those previously diagnosed with functional heartburn. Most patients with NERD, however, could be identified based on their clinical characteristics and response to proton pump inhibitors and/or integrated anti-gastroesophageal reflux therapy. © 2012 The Author. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  5. A novel joint analysis framework improves identification of differentially expressed genes in cross disease transcriptomic analysis

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    Wenyi Qin

    2018-02-01

    Full Text Available Abstract Motivation Detecting differentially expressed (DE genes between disease and normal control group is one of the most common analyses in genome-wide transcriptomic data. Since most studies don’t have a lot of samples, researchers have used meta-analysis to group different datasets for the same disease. Even then, in many cases the statistical power is still not enough. Taking into account the fact that many diseases share the same disease genes, it is desirable to design a statistical framework that can identify diseases’ common and specific DE genes simultaneously to improve the identification power. Results We developed a novel empirical Bayes based mixture model to identify DE genes in specific study by leveraging the shared information across multiple different disease expression data sets. The effectiveness of joint analysis was demonstrated through comprehensive simulation studies and two real data applications. The simulation results showed that our method consistently outperformed single data set analysis and two other meta-analysis methods in identification power. In real data analysis, overall our method demonstrated better identification power in detecting DE genes and prioritized more disease related genes and disease related pathways than single data set analysis. Over 150% more disease related genes are identified by our method in application to Huntington’s disease. We expect that our method would provide researchers a new way of utilizing available data sets from different diseases when sample size of the focused disease is limited.

  6. Gene coexpression measures in large heterogeneous samples using count statistics.

    Science.gov (United States)

    Wang, Y X Rachel; Waterman, Michael S; Huang, Haiyan

    2014-11-18

    With the advent of high-throughput technologies making large-scale gene expression data readily available, developing appropriate computational tools to process these data and distill insights into systems biology has been an important part of the "big data" challenge. Gene coexpression is one of the earliest techniques developed that is still widely in use for functional annotation, pathway analysis, and, most importantly, the reconstruction of gene regulatory networks, based on gene expression data. However, most coexpression measures do not specifically account for local features in expression profiles. For example, it is very likely that the patterns of gene association may change or only exist in a subset of the samples, especially when the samples are pooled from a range of experiments. We propose two new gene coexpression statistics based on counting local patterns of gene expression ranks to take into account the potentially diverse nature of gene interactions. In particular, one of our statistics is designed for time-course data with local dependence structures, such as time series coupled over a subregion of the time domain. We provide asymptotic analysis of their distributions and power, and evaluate their performance against a wide range of existing coexpression measures on simulated and real data. Our new statistics are fast to compute, robust against outliers, and show comparable and often better general performance.

  7. A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.

    Science.gov (United States)

    Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman

    2013-06-01

    To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

  8. Congenital heart disease: a hard case for differential diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    David Gonçalves Nordon

    2012-04-01

    Full Text Available ABSTRACT Congenital heart diseases are important malformations that might compromise not only the patient's survival, but also his/her quality of life. We present the case of a female newborn who presented cardiovascular unbalance and cianosis in spite of her previous month of life without any complication. Her differential diagnosis was rather difficult, due not only to restrictions of exams available for diagnosis, but also to their sensibility and specificity. We discuss such differential diagnosis and the complicated development of the case.

  9. Disease elimination and re-emergence in differential-equation models.

    Science.gov (United States)

    Greenhalgh, Scott; Galvani, Alison P; Medlock, Jan

    2015-12-21

    Traditional differential equation models of disease transmission are often used to predict disease trajectories and evaluate the effectiveness of alternative intervention strategies. However, such models cannot account explicitly for probabilistic events, such as those that dominate dynamics when disease prevalence is low during the elimination and re-emergence phases of an outbreak. To account for the dynamics at low prevalence, i.e. the elimination and risk of disease re-emergence, without the added analytical and computational complexity of a stochastic model, we develop a novel application of control theory. We apply our approach to analyze historical data of measles elimination and re-emergence in Iceland from 1923 to 1938, predicting the temporal trajectory of local measles elimination and re-emerge as a result of disease migration from Copenhagen, Denmark. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

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    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  11. Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

    International Nuclear Information System (INIS)

    Vi, Linda; Feng, Lucy; Zhu, Rebecca D.; Wu, Yan; Satish, Latha; Gan, Bing Siang; O'Gorman, David B.

    2009-01-01

    Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, α smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

  12. DIFFERENTIAL DIAGNOSTICS MODEL RESEARCH BY MEANS OF THE POTENTIAL FUNCTIONS METHOD FOR NEUROLOGY DISEASES CLASSIFICATION

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    V. Z. Stetsyuk

    2016-10-01

    Full Text Available Informatization in medicine offers a lot of opportunities to enhance quality of medical support, accuracy of diagnosis and provides the use of accumulated experience. Modern program systems are utilized now as additional tools to get appropriate advice. This article offers the way to provide help for neurology department doctor of NCSH «OKHMATDYT» during diagnosis determining. It was decided to design the program system for this purpose based on differential diagnostic model. The key problems in differential diagnosis are symptoms similarity between each other in one disease group and the absence of key symptom. Therefore the differential diagnostic model is needed. It is constructed using the potential function method in characteristics space. This characteristics space is formed by 100-200 points - patients with their symptoms. The main feature of this method here is that the decision function is building during recognition step united with learning that became possible with the help of modern powerful computers.

  13. Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

    Science.gov (United States)

    Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Andre, Barbara G; Hess, Ann M; Delorey, Mark J; Pilgard, Mark A; Johnson, Barbara J; Webb, Kristofor; Islam, M Nurul; Pegalajar-Jurado, Adoracion; Molla, Irida; Jewett, Mollie W; Belisle, John T

    2017-08-16

    Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N -acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. The combination of disease and Zheng (syndrome on the basic of differentiation of six channels: a new pattern of disease diagnosis and treatment of traditional Chinese medicine

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    Xue Yang

    2017-04-01

    Full Text Available Traditional Chinese medicine (TCM was formed two thousand years ago, and developed in the following centuries. TCM has a unique way of looking at health and illness. Zheng (syndrome is the basic unit and key term in TCM theory. Zheng is the pathological generalization of a certain stage in the development of disease. Treatment based on syndrome differentiation and disease differentiation of TCM is the basic principle to know and treat diseases,and a kind of special method to study diseases in TCM. In Han Dynasty (200 AD, doctor Zhang Zhongjing proposed Liujing Bianzheng (the differential diagnosis in accordance with the theory of six channels to diagnose and treat diseases in Treatise on Febrile and Miscellaneous Diseases. In other words, he divided diseases into six channels diseases based on patient’s Zhengs. Six channels diseases almost include all of the disease according to his classification standards. In addition, there are development rules in the progress of six channels diseases.Therefore, we hypothesized that combination of six channels disease and Zheng on the basic of differentiation of six channels is a new pattern of diagnosis and treatment diseases in TCM, which is beneficial to the understanding of a certain disease and makes disease treatment more convenient, fast and effective.

  15. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

    Science.gov (United States)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

    2017-11-13

    The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

  16. Visual pigment coexpression in all cones of two rodents, the Siberian hamster, and the pouched mouse.

    Science.gov (United States)

    Lukáts, Akos; Dkhissi-Benyahya, Ouria; Szepessy, Zsuzsanna; Röhlich, Pál; Vígh, Béla; Bennett, Nigel C; Cooper, Howard M; Szél, Agoston

    2002-07-01

    To decide whether the identical topography of short- and middle-wavelength cone photoreceptors in two species of rodents reflects the presence of both opsins in all cone cells. Double-label immunocytochemistry using antibodies directed against short-wavelength (S)-and middle- to long-wavelength (M/L)-sensitive opsin were used to determine the presence of visual pigments in cones of two species of rodents, the Siberian hamster (Phodopus sungorus) and the pouched mouse (Saccostomus campestris) from South Africa. Topographical distribution was determined from retinal whole-mounts, and the colocalization of visual pigments was examined using confocal laser scanning microscopy. Opsin colocalization was also confirmed in consecutive semithin tangential sections. The immunocytochemical results demonstrate that in both the Siberian hamster and the pouched mouse all retinal cones contain two visual pigments. No dorsoventral gradient in the differential expression of the two opsins is observed. The retina of the Siberian hamster and the pouched mouse is the first example to show a uniform coexpression of M and S cone opsins in all cones, without any topographical gradient in opsin expression. This finding makes these two species good models for the study of molecular control mechanisms in opsin coexpression in rodents, and renders them suitable as sources of dual cones for future investigations on the role and neural connections of this cone type.

  17. Differential diagnosis of thyroid diseases with 131I and 201TlCl scintigraphy

    International Nuclear Information System (INIS)

    Kumano, Machiko; Ishida, Osamu

    1979-01-01

    Scintigraphic study with 131 I and 201 TlCl was performed on the differential diagnosis of various kinds of thyroid disease. When thyroid nodules are cold by scintigraphy with 131 I and hot with 201 TlCl, the lesions were proved to be solid tumor, that is, mostly follicular adenoma and carcinoma, and also most probably chronic thyroiditis. Accumulation of 201 TlCl, however, is not observed in cystic lesions, and is very high with high frequency in metastatic lesion of the lymph nodes as well as the thyroid cancer, especially in well differentiated follicular carcinoma. Therefore 201 TlCl was very useful to confirm the metastatic tumors from the thyroid cancer. These features in accumulation of 131 I and 201 TlCl in thyroid disease suggest the imaging technique with 201 TlCl combined with 131 I seem to provide more pathological information on the thyroid and metastatic lesions. (author)

  18. Identification of the Causative Disease of Intermittent Claudication through Walking Motion Analysis: Feature Analysis and Differentiation

    Directory of Open Access Journals (Sweden)

    Tetsuyou Watanabe

    2014-01-01

    Full Text Available Intermittent claudication is a walking symptom. Patients with intermittent claudication experience lower limb pain after walking for a short time. However, rest relieves the pain and allows the patient to walk again. Unfortunately, this symptom predominantly arises from not 1 but 2 different diseases: LSS (lumber spinal canal stenosis and PAD (peripheral arterial disease. Patients with LSS can be subdivided by the affected vertebra into 2 main groups: L4 and L5. It is clinically very important to determine whether patients with intermittent claudication suffer from PAD, L4, or L5. This paper presents a novel SVM- (support vector machine- based methodology for such discrimination/differentiation using minimally required data, simple walking motion data in the sagittal plane. We constructed a simple walking measurement system that is easy to set up and calibrate and suitable for use by nonspecialists in small spaces. We analyzed the obtained gait patterns and derived input parameters for SVM that are also visually detectable and medically meaningful/consistent differentiation features. We present a differentiation methodology utilizing an SVM classifier. Leave-one-out cross-validation of differentiation/classification by this method yielded a total accuracy of 83%.

  19. Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis

    Science.gov (United States)

    Pishdad, P.; Pishdad, G.R.; Tavanaa, S.; Pishdad, R.; Jalli, R.

    2017-01-01

    Objective: Graves’ disease and Hashimoto’s thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves’ disease from Hashimoto’s thyroiditis. Methods: This study included 149 patients divided into three groups, patients with Graves’ disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto’s thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. Results: A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves’ was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto’s group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves’ group with 100% and 17.6% specificity and sensitivity, respectively. Conclusion: Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves’ disease or Hashimoto’s thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed. PMID:28451576

  20. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  1. Differentiation of mucosal disease from partial development of the paranasal sinuses in pediatric patients

    International Nuclear Information System (INIS)

    Duerinckx, A.J.; Whyte, A.M.; Lufkin, R.B.; Hall, T.R.; Kangarloo, H.

    1988-01-01

    On magnetic resonance (MR) images of pediatric patients, sinus mucosal disease may have an appearance similar to that of the normal partially developed sinus, leading to an increase in the number of patients labeled as having incidental sinusitis. The paranasal sinuses were retrospectively evaluated in 27 infants and children aged 0-11 years undergoing brain MR imaging for indications both unrelated and related to sinus disease. The authors developed criteria for grading paranasal sinus development and mucosal disease. Incidental mucosal disease is not uncommon, occurring in 28% of patients aged 0-7 years. In children under 3 years of age, inflammatory mucosal thickening and marrow surrounding the partially developed sinus have a high signal on many MR sequences and may be confused. Recognition of the low-intensity peripheral cortical margin of the sinus and awareness of the stages of normal sinus development allow differentiation

  2. Differential expression of miR-145 in children with Kawasaki disease.

    Directory of Open Access Journals (Sweden)

    Chisato Shimizu

    Full Text Available Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness.RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16. miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005. miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease.Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF

  3. Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

    Science.gov (United States)

    Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X

    2017-05-01

    Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

  4. ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

    Directory of Open Access Journals (Sweden)

    Tina Zimmermann

    2016-10-01

    Full Text Available Huntington's disease (HD is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor. By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA chemical and two genetic HD mouse models (R6/2 and N171-82Q on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by BDNF neural progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed only minor improvements. Tumor formation was absent, and regeneration was attributed to enhanced neuronal and striatal differentiation. In addition, adult neurogenesis was preserved in a BDNF-dependent manner. Our findings provide significant insight for establishing therapeutic strategies for HD to ameliorate neurodegenerative symptoms.

  5. GeneCAT--novel webtools that combine BLAST and co-expression analyses

    DEFF Research Database (Denmark)

    Mutwil, Marek; Obro, Jens; Willats, William G T

    2008-01-01

    The gene co-expression analysis toolbox (GeneCAT) introduces several novel microarray data analyzing tools. First, the multigene co-expression analysis, combined with co-expressed gene networks, provides a more powerful data mining technique than standard, single-gene co-expression analysis. Second...... orthologs in the plant model organisms Arabidopsis thaliana and Hordeum vulgare (Barley). GeneCAT is equipped with expression data for the model plant A. thaliana, and first to introduce co-expression mining tools for the monocot Barley. GeneCAT is available at http://genecat.mpg.de....

  6. Coexpression of multidrug resistance involve proteins: a flow cytometric analysis.

    Science.gov (United States)

    Boutonnat, J; Bonnefoix, T; Mousseau, M; Seigneurin, D; Ronot, X

    1998-01-01

    Cross resistance to multiple natural cytotoxic products represents a major obstacle in myeloblastic acute leukaemia (AML). Multidrug resistance (MDR) often involves overexpression of plasma membrane drug transporter P-glycoprotein (PGP) or the resistance associated protein (MRP). Recently, a protein overexpressed in a non-PGP MDR lung cancer cell line and termed lung resistance related protein (LRP) was identified. These proteins are known to be associated with a bad prognosis in AML. We have developed a triple indirect labelling analysed by flow cytometry to detect the coexpression of these proteins. Since no cell line expressing all three antigens is known, we mixed K562 cells (resistant to Adriblastine, PGP+, MRP-, LRP-) with GLC4 cells (resistant to Adriblastine, PGP-, MRP+, LRP+) to create a model system to test the method. The antibodies used were UIC2 for PGP, MRPm6 for MRP and LRP56 for LRP. They were revealed by Fab'2 coupled with Fluoresceine-isothiocyanate, Phycoerythrin or Tricolor with isotype specificity. Cells were fixed and permeabilized after PGP labelling because MRPm6 and LRP56 recognize intracellular epitopes. PGP and LRP were easily detected. MRP is expressed at relatively low levels and was more difficult to detect because in the triple labelling the non specific staining was higher than in a single labelling. Despite the increased background in the triple labelling we were able to detect coexpression of PGP, MRP, LRP by flow cytometry. This method appears to be very useful to detect coexpression of markers in AML. Such coexpression could modify the therapeutic approach with revertants.

  7. CT findings of pleural lesions: differential diagnosis between malignant benign diseases

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Yon; Lim, Tae Hwan; Kim, Woo Sun; Park, Kwang Gil [Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of)

    1991-05-15

    A number of benign and malignant diseases may cause pleural abnormalities. Since the resolution of computed tomography (CT) has been improved, the detailed anatomy of pleura can now be well delineated in various pleural diseases. We reviewed retrospectively the CT findings of 60 patients with pathologically proved pleural diseases in order to find out the differential points between benign and malignant diseases. Thirty-six patients had malignant diseases (20 adenocarcinoma, 8 squamous cell carcinoma, 4 small cell carcinoma, 2 lung metastasis, 1 large cell carcinoma, 1 small and large cell carcinoma), and 24 patients had benign diseases (16 tuberculosis including empyema, 3 bacterial empyema, 3 pneumonia, 1 lung abscess, 1 lung contusion). The CT features that suggested malignant pleural diseases were high-grade mediastinal involvement (57.9%, {rho} < 0.1), thick and irregular thickening with nodularity and mass formations (38.5%, {rho} < 0.1), Circumferential pleural thickening 132.1%, {rho} < 0.01), and aggressive pleural effusion 122.2%, {rho} < 0.05). Benign pleural lesions were typically represented by pleural calcification (50%) and extrapleural fat accumulation (45.8%)

  8. Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

    Science.gov (United States)

    Scriba, Thomas J; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S Lindestam

    2017-09-15

    Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

  9. Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Kim, Young Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

    1998-03-01

    The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs.

  10. Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

    International Nuclear Information System (INIS)

    Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung

    1998-01-01

    The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs

  11. Differential Diagnosis of Erythmato-Squamous Diseases Using Classification and Regression Tree.

    Science.gov (United States)

    Maghooli, Keivan; Langarizadeh, Mostafa; Shahmoradi, Leila; Habibi-Koolaee, Mahdi; Jebraeily, Mohamad; Bouraghi, Hamid

    2016-10-01

    Differential diagnosis of Erythmato-Squamous Diseases (ESD) is a major challenge in the field of dermatology. The ESD diseases are placed into six different classes. Data mining is the process for detection of hidden patterns. In the case of ESD, data mining help us to predict the diseases. Different algorithms were developed for this purpose. we aimed to use the Classification and Regression Tree (CART) to predict differential diagnosis of ESD. we used the Cross Industry Standard Process for Data Mining (CRISP-DM) methodology. For this purpose, the dermatology data set from machine learning repository, UCI was obtained. The Clementine 12.0 software from IBM Company was used for modelling. In order to evaluation of the model we calculate the accuracy, sensitivity and specificity of the model. The proposed model had an accuracy of 94.84% (. 24.42) in order to correct prediction of the ESD disease. Results indicated that using of this classifier could be useful. But, it would be strongly recommended that the combination of machine learning methods could be more useful in terms of prediction of ESD.

  12. Usefulness of pinhole collimator in differential diagnosis of metastatic disease and degenerative joint disease in the vertebrae

    International Nuclear Information System (INIS)

    Kosuda, Shigeru; Kawahara, Syunji; Ishibashi, Akihiko; Tamura, Kohei; Tsukatani, Yasushi; Fujii, Hiroshi; Kubo, Atsushi; Hashimoto, Shozo.

    1989-01-01

    In order to evaluate the diagnostic efficacy of pinhole collimator (PHC) imaging combined with an X-ray for vertebral metastasis, our prospective study has employed receiver operating characteristics (ROC) analysis in 21 patients, 11 with osseous metastasis and 15 with degenerative joint disease in the lumbar vertebrae. PHC imaging provided better anatomic information on the extent of 99m Tc-MDP accumulation. PHC vertebral scintigraphy had a considerable impact on the decision-making process, although with variations and not very satisfactory results among the physicians with little experience. Our study suggests that PHC imaging and X-ray film are useful in differentiating between osseous metastasis and degenerative joint disease in the vertebra. (author)

  13. Radionuclide and differential radiodiagnosis of renal parenchymal tumors versus nontumorous renal diseases

    International Nuclear Information System (INIS)

    Khripta, F.P.

    1981-01-01

    Modern radiation semiotics of kidney parenchyma cancer and nontumoural diseases of kidney parenchyma is described. Their new indices are shown, the place and significance of radionuclide and roentgenologic methods for the differential diagnosis of kidney parenchyma cancer and nontumoural kidney parenchyma diseases are shown. The plan described is nowadays one of the most rational diagrams. The diagnostic value of roen-- tgenologic and radionuclide investigations of kidney parenchyma cancer is not equivalent. Radio-indication methods state changes which are not characteristic of a particular disease. Therefore, they are used as tests for the further purpose ful special roentgenologic investigation with the minimum traumaticity which improves the diagnosis of kidney parenchyma cancer and permits to reduce investigation periods and material expenditure [ru

  14. Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Gmitterová, K; Heinemann, U; Krasnianski, A; Gawinecka, J; Zerr, I

    2016-06-01

    Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P disease duration and clinical stage influenced the test sensitivity in all proteins. Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known. © 2016 EAN.

  15. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon.

    Science.gov (United States)

    Wu, Po-Chang; Huang, Min-Nung; Kuo, Yu-Min; Hsieh, Song-Chou; Yu, Chia-Li

    2013-08-01

    Nailfold capillaroscopy is a useful tool to distinguish primary from secondary Raynaud's phenomenon (RP) by examining the morphology of nailfold capillaries but its role in disease diagnosis is not clearly established. The purpose of this study was to evaluate the roles of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases (CTDs) with RP. The data between the year 2005 and 2009 were retrieved from the nailfold capillaroscopic database of National Taiwan University Hospital (NTUH). Only the data from the patients with RP were analyzed. The criteria for interpretation of capillaroscopic findings were predefined. The final diagnoses of the patients were based on the American College of Rheumatology classification criteria for individual diseases, independent of nailfold capillaroscopic findings. The sensitivity and the specificity of each capillaroscopic pattern to the diseases were determined. The data from a total of 67 patients were qualified for the current study. We found the sensitivity and specificity of scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the specificity of the early, active, and late scleroderma patterns for SSc reached 87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for MCTD were 20%/100%. The nailfold capillaroscopic (NC) patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity. Copyright © 2012. Published by Elsevier B.V.

  16. NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

    Science.gov (United States)

    Kostara, Christina E; Papathanasiou, Athanasios; Psychogios, Nikolaos; Cung, Manh Thong; Elisaf, Moses S; Goudevenos, John; Bairaktari, Eleni T

    2014-05-02

    Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

  17. Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Fenming Zhang

    Full Text Available To explore the diagnostic models of Crohn's disease (CD, Intestinal tuberculosis (ITB and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles.Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05. Genetic algorithm combining with support vector machine (SVM was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO cross validation method.There were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05 to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900 can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210 can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541 can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80

  18. Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery.

    Science.gov (United States)

    Jia, Zhilong; Liu, Ying; Guan, Naiyang; Bo, Xiaochen; Luo, Zhigang; Barnes, Michael R

    2016-05-27

    Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and

  19. Differentiation between mild cognitive impairment, Alzheimer's disease and depression by means of cued recall.

    Science.gov (United States)

    Dierckx, E; Engelborghs, S; De Raedt, R; De Deyn, P P; Ponjaert-Kristoffersen, I

    2007-05-01

    Discriminating Alzheimer's disease (AD) and mild cognitive impairment (MCI) from depression is a challenge in psychogeriatric medicine. A study was set up to ascertain whether cued recall could be useful in differentiating early AD and MCI from depression among elderly individuals. The Visual Association Test (VAT) and the Memory Impairment Screen-plus (MIS-plus) were administered together with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) to 40 MCI patients, 35 mild AD patients, 46 depressed patients and 52 healthy control subjects. A one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests showed that AD patients had significantly lower cued recall scores (i.e. combined VAT and MIS-plus scores) than MCI patients, who in turn had lower scores than depressed patients. The scores of depressed patients and controls were not significantly different. Discriminant analysis revealed that 94% of the AD patients and 96% of the depressed patients could be classified correctly by means of the GDS and the cued recall sores. Receiver operating characteristic (ROC) curves identified an optimal cut-off score of 8 (maximum score 12) for differentiating AD and MCI patients from depressed elderly patients and controls. Applying this cut-off, a sensitivity of 83% (58%) and a specificity of 85% (85%) was obtained when differentiating AD (MCI) from depression. Cued recall, operationalized by the combined scores of VAT and MIS-plus, is a useful method for differentiating AD patients from depressed individuals and healthy controls. Probably because of the great heterogeneity among MCI patients, the diagnostic power of cued recall decreases when applied to differentiate MCI from depression.

  20. Ethnic and Gender Differentials in Non-Communicable Diseases and Self-Rated Health in Malaysia

    Science.gov (United States)

    Teh, Jane K. L.; Tey, Nai Peng; Ng, Sor Tho

    2014-01-01

    Objectives This paper examines the ethnic and gender differentials in high blood pressure (HBP), diabetes, coronary heart disease (CHD), arthritis and asthma among older people in Malaysia, and how these diseases along with other factors affect self-rated health. Differentials in the prevalence of non-communicable diseases among older people are examined in the context of socio-cultural perspectives in multi-ethnic Malaysia. Methods Data for this paper are obtained from the 2004 Malaysian Population and Family Survey. The survey covered a nationally representative sample of 3,406 persons aged 50 and over, comprising three main ethnic groups (Malays, Chinese and Indians) and all other indigenous groups. Bivariate analyses and hierarchical logistic regression were used in the analyses. Results Arthritis was the most common non-communicable disease (NCD), followed by HBP, diabetes, asthma and CHD. Older females were more likely than males to have arthritis and HBP, but males were more likely to have asthma. Diabetes and CHD were most prevalent among Indians, while arthritis and HBP were most prevalent among the Indigenous groups. Older people were more likely to report poor health if they suffered from NCD, especially CHD. Controlling for socio-economic, health and lifestyle factors, Chinese were least likely to report poor health, whereas Indians and Indigenous people were more likely to do so. Chinese that had HBP were more likely to report poor health compared to other ethnic groups with the same disease. Among those with arthritis, Indians were more likely to report poor health. Conclusion Perceived health status and prevalence of arthritis, HBP, diabetes, asthma and CHD varied widely across ethnic groups. Promotion of healthy lifestyle, early detection and timely intervention of NCDs affecting different ethnic groups and gender with socio-cultural orientations would go a long way in alleviating the debilitating effects of the common NCDs among older people. PMID

  1. Ethnic and gender differentials in non-communicable diseases and self-rated health in Malaysia.

    Science.gov (United States)

    Teh, Jane K L; Tey, Nai Peng; Ng, Sor Tho

    2014-01-01

    This paper examines the ethnic and gender differentials in high blood pressure (HBP), diabetes, coronary heart disease (CHD), arthritis and asthma among older people in Malaysia, and how these diseases along with other factors affect self-rated health. Differentials in the prevalence of non-communicable diseases among older people are examined in the context of socio-cultural perspectives in multi-ethnic Malaysia. Data for this paper are obtained from the 2004 Malaysian Population and Family Survey. The survey covered a nationally representative sample of 3,406 persons aged 50 and over, comprising three main ethnic groups (Malays, Chinese and Indians) and all other indigenous groups. Bivariate analyses and hierarchical logistic regression were used in the analyses. Arthritis was the most common non-communicable disease (NCD), followed by HBP, diabetes, asthma and CHD. Older females were more likely than males to have arthritis and HBP, but males were more likely to have asthma. Diabetes and CHD were most prevalent among Indians, while arthritis and HBP were most prevalent among the Indigenous groups. Older people were more likely to report poor health if they suffered from NCD, especially CHD. Controlling for socio-economic, health and lifestyle factors, Chinese were least likely to report poor health, whereas Indians and Indigenous people were more likely to do so. Chinese that had HBP were more likely to report poor health compared to other ethnic groups with the same disease. Among those with arthritis, Indians were more likely to report poor health. Perceived health status and prevalence of arthritis, HBP, diabetes, asthma and CHD varied widely across ethnic groups. Promotion of healthy lifestyle, early detection and timely intervention of NCDs affecting different ethnic groups and gender with socio-cultural orientations would go a long way in alleviating the debilitating effects of the common NCDs among older people.

  2. Ethnic and gender differentials in non-communicable diseases and self-rated health in Malaysia.

    Directory of Open Access Journals (Sweden)

    Jane K L Teh

    Full Text Available This paper examines the ethnic and gender differentials in high blood pressure (HBP, diabetes, coronary heart disease (CHD, arthritis and asthma among older people in Malaysia, and how these diseases along with other factors affect self-rated health. Differentials in the prevalence of non-communicable diseases among older people are examined in the context of socio-cultural perspectives in multi-ethnic Malaysia.Data for this paper are obtained from the 2004 Malaysian Population and Family Survey. The survey covered a nationally representative sample of 3,406 persons aged 50 and over, comprising three main ethnic groups (Malays, Chinese and Indians and all other indigenous groups. Bivariate analyses and hierarchical logistic regression were used in the analyses.Arthritis was the most common non-communicable disease (NCD, followed by HBP, diabetes, asthma and CHD. Older females were more likely than males to have arthritis and HBP, but males were more likely to have asthma. Diabetes and CHD were most prevalent among Indians, while arthritis and HBP were most prevalent among the Indigenous groups. Older people were more likely to report poor health if they suffered from NCD, especially CHD. Controlling for socio-economic, health and lifestyle factors, Chinese were least likely to report poor health, whereas Indians and Indigenous people were more likely to do so. Chinese that had HBP were more likely to report poor health compared to other ethnic groups with the same disease. Among those with arthritis, Indians were more likely to report poor health.Perceived health status and prevalence of arthritis, HBP, diabetes, asthma and CHD varied widely across ethnic groups. Promotion of healthy lifestyle, early detection and timely intervention of NCDs affecting different ethnic groups and gender with socio-cultural orientations would go a long way in alleviating the debilitating effects of the common NCDs among older people.

  3. Differential diagnosis of metastatic bone disease and benign bone disease on spine SPECT in patients with low back pain

    International Nuclear Information System (INIS)

    Lee, Seung Hun; Choi, Yun Young; Cho, Suk Shin

    2001-01-01

    One or more abnormal vertebrae detected on bone scintigraphy is a common finding in clinical practice, and it could pose a diagnostic dilemma especially in cancer patients, as either metastasis or benign disease may cause scintigraphic abnormality. The purpose of this study was to determine whether additional spine SPECT has a role in differentiating malignant from benign lesions in patients with back pain. We reviewed spine SPECT studies obtained over a three-year period in 108 patients. Among them, forty-five patients with abnormal SPECT and clinically followed records were evaluated (20 cancer patients were included). Uptake patterns were classified as follows: 1. Body: diffusely increased uptake, linear increased uptake of end plate, segmental increased uptake, and cold defect, 2 Posterior element; posterior to body (pedicle), posterior to intervertebral disc space (facet joint), and spinous process. Lesions were correlated with radiological findings and with final diagnosis. Sixty-nine bone lesions were detected on SPECT images, including 18 metastases, 28 degenerative diseases and 21 compression fractures. Cold defect (6) and segmental increased uptake (5) were dominant findings in metastasis: linear increased uptake (12), and facet joint uptake (15) were in degenerative change; and diffuse increased uptake (9), and linear increased uptake (9) were in compression fracture. Cold defect and segmental increased uptake of body were characteristic findings of metastasis, but care should be taken because compression fracture also shows segmental increased uptake in some cases. Degenerative disease was easily diagnosed because of the typical finding of linear increased uptake of end plate and facet joint. Therefore, additional bone SPECT after planar bone scan would be helpful for differentiating metastasis from benign condition in cancer patients

  4. Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

    Science.gov (United States)

    Donkol, Ragab Hani; Nada, Aml Mohamed; Boughattas, Sami

    2013-01-01

    AIM: To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS: Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups: 18 cases with Graves’ disease and 8 cases with Hashimoto’s thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves’ disease and Hashimoto’s thyroiditis was supported by the clinical picture and follow up of patients. RESULTS: Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves’ disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION: Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients. PMID:23671754

  5. Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study

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    Min Ji Jeon

    2017-11-01

    Full Text Available BackgroundLittle is known regarding disease-specific mortality of differentiated thyroid cancer (DTC patients and its risk factors in Korea.MethodsWe retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.ResultsMean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97% and underwent total thyroidectomy (85%. Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9% occurred; the 10-year disease-specific survival (DSS rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%. Older age (≥45 years at diagnosis, male, follicular thyroid cancer (FTC versus PTC, larger tumor size (>2 cm, presence of extrathyroidal extension (ETE, lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM stage were independent risk factors of disease-specific mortality of DTC patients.ConclusionThe rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

  6. (131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

    Science.gov (United States)

    Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

    2016-01-01

    Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  7. Immunological functioning in Alzheimer's disease: differential effects of relative left versus right temporoparietal dysfunction.

    Science.gov (United States)

    Foster, Paul S; Roosa, Katelyn M; Williams, Megan R; Witt, John C; Heilman, Kenneth M; Drago, Valeria

    2013-10-15

    The cerebral hemispheres are differentially involved in regulating immunological functioning and the neuropathology associated with Alzheimer's disease (AD) is asymmetrical. Thus, subgroups of AD patients may exhibit different patterns of immunological dysfunction. We explored this possibility in a group of AD patients and found that patients with low white blood cell counts and low lymphocyte numbers exhibited better performance on tests of right temporoparietal functioning. Also, a significant positive relationship exists between lymph numbers and performance on a test of left temporoparietal functioning. Thus, some AD patients have greater immunological dysfunction based on relative left versus right temporoparietal functioning. © 2013.

  8. Differential Control Efficacies of Vitamin Treatments against Bacterial Wilt and Grey Mould Diseases in Tomato Plants

    Directory of Open Access Journals (Sweden)

    Jeum Kyu Hong

    2016-10-01

    Full Text Available Bacterial wilt and grey mould in tomato plants are economically destructive bacterial and fungal diseases caused by Ralstonia solanacearum and Botrytis cinerea, respectively. Various approaches including chemical and biological controls have been attempted to arrest the tomato diseases so far. In this study, in vitro growths of bacterial R. solanacearum and fungal B. cinerea were evaluated using four different vitamins including thiamine (vitamin B1, niacin (vitamin B3, pyridoxine (vitamin B6, and menadione (vitamin K3. In planta efficacies of the four vitamin treatments on tomato protection against both diseases were also demonstrated. All four vitamins showed different in vitro antibacterial activities against R. solanacearum in dose-dependent manners. However, treatment with 2 mM thiamine was only effective in reducing bacterial wilt of detached tomato leaves without phytotoxicity under lower disease pressure (10⁶ colony-forming unit [cfu]/ml. Treatment with the vitamins also differentially reduced in vitro conidial germination and mycelial growth of B. cinerea. The four vitamins slightly reduced the conidial germination, and thiamine, pyridoxine and menadione inhibited the mycelial growth of B. cinerea. Menadione began to drastically suppress the conidial germination and mycelial growth by 5 and 0.5 mM, respectively. Grey mould symptoms on the inoculated tomato leaves were significantly reduced by pyridoxine and menadione pretreatments one day prior to the fungal challenge inoculation. These findings suggest that disease-specific vitamin treatment will be integrated for eco-friendly management of tomato bacterial wilt and grey mould.

  9. Differential Control Efficacies of Vitamin Treatments against Bacterial Wilt and Grey Mould Diseases in Tomato Plants.

    Science.gov (United States)

    Hong, Jeum Kyu; Kim, Hyeon Ji; Jung, Heesoo; Yang, Hye Ji; Kim, Do Hoon; Sung, Chang Hyun; Park, Chang-Jin; Chang, Seog Won

    2016-10-01

    Bacterial wilt and grey mould in tomato plants are economically destructive bacterial and fungal diseases caused by Ralstonia solanacearum and Botrytis cinerea , respectively. Various approaches including chemical and biological controls have been attempted to arrest the tomato diseases so far. In this study, in vitro growths of bacterial R. solanacearum and fungal B. cinerea were evaluated using four different vitamins including thiamine (vitamin B1), niacin (vitamin B3), pyridoxine (vitamin B6), and menadione (vitamin K3). In planta efficacies of the four vitamin treatments on tomato protection against both diseases were also demonstrated. All four vitamins showed different in vitro antibacterial activities against R. solanacearum in dose-dependent manners. However, treatment with 2 mM thiamine was only effective in reducing bacterial wilt of detached tomato leaves without phytotoxicity under lower disease pressure (10 6 colony-forming unit [cfu]/ml). Treatment with the vitamins also differentially reduced in vitro conidial germination and mycelial growth of B. cinerea . The four vitamins slightly reduced the conidial germination, and thiamine, pyridoxine and menadione inhibited the mycelial growth of B. cinerea . Menadione began to drastically suppress the conidial germination and mycelial growth by 5 and 0.5 mM, respectively. Grey mould symptoms on the inoculated tomato leaves were significantly reduced by pyridoxine and menadione pretreatments one day prior to the fungal challenge inoculation. These findings suggest that disease-specific vitamin treatment will be integrated for eco-friendly management of tomato bacterial wilt and grey mould.

  10. Tuberculosis in pregnancy:a challenging differential diagnosisfor inflammatory bowel disease.

    Science.gov (United States)

    Santana, E F M; Araujo Júnior, E; Campanharo, F F; Sarmento, S G P; Saito, C S; Moron, F A

    2014-08-01

    To describe a case of tuberculosis with intestinal variant in a pregnant woman in the 17th week of pregnancy. Case report. Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo-SP, Brazil. Tuberculosis is a public health problem that concerns many countries in the world. It was declareda public emergency by the World Health Organization in 2005. Its presence during pregnancy brings maternal risk and fetal impairment if not treated quickly and properly. The intestinal variant is not the most common form of the disease and may be confused with inflammatory bowel diseases, especially Crohns disease. Knowledge of the specific characteristics, combined with a detailed medical history and appropriate diagnostic methods can make all the difference in gestational prognosis. We report the case of a pregnant woman who wrongly underwent treatment for inflammatory bowel disease at another service. After admission to our university hospital, fruitful diagnostic clarification was achieved and the patient was diagnosed and treated for tuberculosis. We describe the details of the investigation and, in particular, review the main characteristics in the literature for differentiating the two diseases.

  11. Ultrasonographic differentiation between Kikuchi's disease and lymphoma in patients with cervical lymphadenopathy

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Wu-Chia [Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan (China); Chang, Wen-Cheng [Department of Pediatrics, Far Eastern Memorial Hospital, Taipei, Taiwan (China); Lin, Yu-Chin [Department of Medical Oncology and Hematology, Far Eastern Memorial Hospital, Taipei, Taiwan (China); Hsu, Yao-Peng [Department of Anatomic Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan (China); Liao, Li-Jen, E-mail: liaolj@ntu.edu.tw [Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan (China); Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China)

    2012-08-15

    characteristics (size, shape, rims, matting and echotexture) helps differentiate cervical lymph nodes in patients with Kikuchi's disease and lymphoma. Cervical lymphadenopathies in patients with Kikuchi's disease have smaller size, less round, less micronodular reticular echotexture, and more signs of matting and cortical widening than those with lymphoma examined under ultrasound.

  12. Ultrasonographic differentiation between Kikuchi's disease and lymphoma in patients with cervical lymphadenopathy

    International Nuclear Information System (INIS)

    Lo, Wu-Chia; Chang, Wen-Cheng; Lin, Yu-Chin; Hsu, Yao-Peng; Liao, Li-Jen

    2012-01-01

    Purpose: Kikuchi's disease, or histiocytic necrotizing lymphadenitis, is a self-limited necrotizing lymphadenitis. Clinically, it resembles lymphoma. We want to compare the sonographic features between Kikuchi's disease and lymphoma in patients with cervical lymphadenopathy. Materials and methods: The study protocol was approved by the institutional review board. Two hundred and twenty six cervical lymph nodes (137 nodes from 21 Kikuchi's disease patients and 89 nodes from 20 malignant lymphoma patients) were examined. The demographic and ultrasonographic characteristics of lymph nodes were collected and analyzed. Results: The Kikuchi's disease patients (mean age, 24.2 years; range, 8–57 years) were younger than those with lymphoma (mean age, 54 years; range, 13–81 years). There was no difference in laterality of nodes (p = 0.19). The nodal distribution demonstrated most enlarged neck lymph nodes located at level II, III and V. The ranges of short-axis and long-axis length were 6.5 ± 2.3 mm (mean ± SD) versus 13.4 ± 5.1 mm and 13.4 ± 5.0 mm versus 21.2 ± 9.2 mm for Kikuchi's disease versus lymphoma (p 0.05). Conclusion: Analysis of basic ultrasonographic characteristics (size, shape, rims, matting and echotexture) helps differentiate cervical lymph nodes in patients with Kikuchi's disease and lymphoma. Cervical lymphadenopathies in patients with Kikuchi's disease have smaller size, less round, less micronodular reticular echotexture, and more signs of matting and cortical widening than those with lymphoma examined under ultrasound.

  13. Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine.

    Science.gov (United States)

    Sriphrapradang, Chutintorn; Bhasipol, Adikan

    2016-09-01

    The measurement of free thyroid hormone, instead of the total form, is more commonly used in current practice. We aimed to evaluate the usefulness of the ratio of serum free triiodothyronine (FT3, pg/mL) to free thyroxine (FT4, ng/dL) for differentiating Graves' disease from subacute thyroiditis. Medical records of thyrotoxic patients aged >15 years who had measurement of FT3, FT4 and thyrotropin on the first diagnosis of thyrotoxicosis before initiating treatment were retrospectively reviewed. Data were collected from all clinics, and were not limited to the endocrine clinic. Pregnant women were excluded. A total of 548 patients (468 with Graves' disease, 40 with subacute thyroiditis and 40 with toxic adenoma/multinodular goiter) were recruited. Mean age was 43.9 ± 15.4 years. Most were female 434 (79.2%), and goiter was present in 55.3%. Prevalence of T3-toxicosis and T4-toxicosis were 5.6% and 6.6%, respectively. Mean FT3/FT4 ratios were 4.62 ± 2 (10(-2) pg/ng) in patients with Graves' disease and 2.73 ± 0.5 in subacute thyroiditis. The area under the ROC curve of the FT3/FT4 ratio for diagnosis of Graves' disease was 0.83 (95%CI, 0.76-0.91). Cutoff level of this ratio >4.4 offered sensitivity of 47.2% and specificity of 92.8%. FT3/FT4 ratio of >4.4 (10(-2) pg/ng) may help in differentiating the cause of thyrotoxicosis.

  14. [Retrospective analysis of influence of differential protein intake on renal prognosis for progressive chronic kidney disease].

    Science.gov (United States)

    Dai, Wendi; Yin, Daoxin; Cui, Wenying; Liu, Wenhu

    2014-01-28

    To explore retrospectively the influence of differential protein intake on renal prognosis for progressive chronic kidney disease (CKD). A total of 159 chronic kidney disease patients at stages 2, 3 and 4 were enrolled and a questionnaire survey was conducted from January 2009 to July 2012. They were followed monthly and their clinical data collected, including primary disease, blood pressure, body mass index and adverse events. Laboratory tests were performed every 3 months, including biochemical parameters, protein-energy malnutrition (PEM), diet reviews and daily protein intake (DPI). A simplified MDRD formula was employed to evaluate the level of estimated glomerular filtration rate (eGFR). According to the level of DPI, they were divided into 3 groups of very low protein diet (VLPD): DPI ≤ 0.6 g · kg(-1) · d(-1), low-protein diet (LPD): DPI >0.6-protein diet (NPD): DPI ≥ 0.8 · g · kg(-1) · d(-1). Among them, 4 cases (2.50%) progressed to uremia stage and received renal replacement therapy, 2(1.25%) experienced rapid decline in renal function, 9(5.66%) were hospitalized from cardio-cerebral diseases and the 2-year kidney survival rate was 97.5%. At the end of study, among 9 patients of PEM, 2 subjects had a serum level of albumin under 32 g/L and another 7 with a BMI 0.05). Within a certain range, differential protein intake may not significantly affect the prognosis of kidney for progressive CKD patients.

  15. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    International Nuclear Information System (INIS)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico; Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio; Russo, Camilla; Feriozzi, Sandro; Veroux, Massimiliano; Battaglia, Yuri; Concolino, Daniela; Pieruzzi, Federico; Tuttolomondo, Antonino; Caronia, Aurelio; Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo

    2017-01-01

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  16. Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

    Science.gov (United States)

    Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

    2017-07-01

    Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  17. Role of neuropsychological assessment in the differential diagnosis of Alzheimer's disease and vascular dementia

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    Érica Maria Lima Pimentel

    Full Text Available Abstract The prevalence of dementia increases significantly from the age of 65 years, doubling every five years thereafter. Alzheimer's disease (AD and vascular dementia (VaD constitute the two main dementia types. Differentiating them encompasses anamnesis, neurological examination, laboratory and neuroimaging exams and neuropsychological assessment. Neuropsychological assessment produces different findings for each dementia type, and reveals those areas most impaired as well as those most preserved. The aim of the present article was to describe the role of neuropsychology in diagnosing dementia and achieving a differential diagnosis between AD and VaD. A general overview follows of the most widely known instruments used to assess cognitive function in dementia, and the cognitive changes seen in AD and VaD. The conclusion drawn was that there is significant overlap in cognitive changes between both these dementia types, while each type has its own specific characteristics which are identifiable and quantifiable on neuropsychological assessments and provide the basis for reaching a differential diagnosis.

  18. Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

    Science.gov (United States)

    Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

    2015-09-01

    Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all Pdisease, especially when the plasma ACTH level alone is not conclusive.

  19. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

    2017-06-15

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  20. Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2012-01-01

    Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

  1. Estimation of the proteomic cancer co-expression sub networks by using association estimators.

    Directory of Open Access Journals (Sweden)

    Cihat Erdoğan

    Full Text Available In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA. Correlation and mutual information (MI based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET and the Molecular Signatures Database (MSigDB was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink and 64% for Schurmann-Grassberger (SG association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.

  2. Plasma Biomarkers Differentiate Parkinson’s Disease From Atypical Parkinsonism Syndromes

    Directory of Open Access Journals (Sweden)

    Chin-Hsien Lin

    2018-04-01

    Full Text Available Objective: Parkinson’s disease (PD has significant clinical overlaps with atypical parkinsonism syndromes (APS, which have a poorer treatment response and a more aggressive course than PD. We aimed to identify plasma biomarkers to differentiate PD from APS.Methods: Plasma samples (n = 204 were obtained from healthy controls and from patients with PD, dementia with Lewy bodies (DLB, multiple system atrophy, progressive supranuclear palsy (PSP, corticobasal degeneration (CBD, or frontotemporal dementia (FTD with parkinsonism (FTD-P or without parkinsonism. We measured plasma levels of α-synuclein, total tau, p-Tau181, and amyloid beta 42 (Aβ42 by immunomagnetic reduction-based immunoassay.Results: Plasma α-synuclein level was significantly increased in patients with PD and APS when compared with controls and FTD without parkinsonism (p < 0.01. Total tau and p-Tau181 were significantly increased in all disease groups compared to controls, especially in patients with FTD (p < 0.01. A multivariate and receiver operating characteristic curve analysis revealed that a cut-off value for Aβ42 multiplied by p-Tau181 for discriminating patients with FTD from patients with PD and APS was 92.66 (pg/ml2, with an area under the curve (AUC of 0.932. An α-synuclein cut-off of 0.1977 pg/ml could separate FTD-P from FTD without parkinsonism (AUC 0.947. In patients with predominant parkinsonism, an α-synuclein cut-off of 1.388 pg/ml differentiated patients with PD from those with APS (AUC 0.87.Conclusion: Our results suggest that integrated plasma biomarkers improve the differential diagnosis of PD from APS (PSP, CBD, DLB, and FTD-P.

  3. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression.

    Directory of Open Access Journals (Sweden)

    James J Zhu

    Full Text Available Foot-and-mouth disease virus (FMDV targets specific tissues for primary infection, secondary high-titer replication (e.g. foot and mouth where it causes typical vesicular lesions and long-term persistence at some primary replication sites. Although integrin αVβ6 receptor has been identified as primary FMDV receptors in animals, their tissue distribution alone fails to explain these highly selective tropism-driven events. Thus, other molecular mechanisms must play roles in determining this tissue specificity. We hypothesized that differences in certain biological activities due to differential gene expression determine FMDV tropism and applied whole genome gene expression profiling to identify genes differentially expressed between FMDV-targeted and non-targeted tissues in terms of supporting primary infection, secondary replication including vesicular lesions, and persistence. Using statistical and bioinformatic tools to analyze the differential gene expression, we identified mechanisms that could explain FMDV tissue tropism based on its association with differential expression of integrin αVβ6 heterodimeric receptor (FMDV receptor, fibronectin (ligand of the receptor, IL-1 cytokines, death receptors and the ligands, and multiple genes in the biological pathways involved in extracellular matrix turnover and interferon signaling found in this study. Our results together with reported findings indicate that differences in (1 FMDV receptor availability and accessibility, (2 type I interferon-inducible immune response, and (3 ability to clear virus infected cells via death receptor signaling play roles in determining FMDV tissue tropism and the additional increase of high extracellular matrix turnover induced by FMDV infection, likely via triggering the signaling of highly expressed IL-1 cytokines, play a key role in the pathogenesis of vesicular lesions.

  4. Perfusion SPECT studies with mapping of Brodmann areas in differentiating Alzheimer's disease from frontotemporal degeneration syndromes.

    Science.gov (United States)

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2012-12-01

    The aim of this study was to evaluate the contribution of brain perfusion single-photon emission computed tomography (SPECT) studies with mapping of Brodmann areas (BAs) in the differential diagnosis between Alzheimer's disease (AD) and frontotemporal degeneration (FTLD) syndromes. Thirty-nine patients with AD and 73 patients with FTLD syndromes [behavioural variant FTLD (bvFTLD); language variant FTLD (lvFTLD), including semantic dementia (SD) and progressive nonfluent aphasia (PNFA); and corticobasal degeneration (CBD)/progressive supranuclear palsy (PSP) syndromes] underwent brain perfusion SPECT. The NeuroGam software was used for the semiquantitative evaluation of perfusion in BAs of the left (L) and right (R) hemispheres. Compared with those in AD patients, BAs with statistically significant hypoperfusion were found in the prefrontal, orbitofrontal and cingulated cortices and Broca's areas of FTLD and bvFTLD patients; in the temporal and prefrontal cortices and Broca's areas of lvFTLD patients; in the left temporal gyrus of SD patients; in premotor and supplementary motor, prefrontal, orbitofrontal, temporal and anterior cingulated cortices and Broca's areas of PNFA patients; and in the prefrontal, temporal, posterior cingulated and primary and secondary visual cortices of CBD/PSP patients. BA 46R could differentiate AD patients from FTLD and bvFTLD patients; 21L and 25L were found to be independent predictors for lvFTLD in comparison with AD, and 25R, 21L and 23R could differentiate AD patients from PNFA, SD and CBD/PSP patients, respectively. Brain perfusion SPECT with BA mapping in AD and FTLD patients could improve the definition of brain areas that are specifically implicated in these disorders, resulting in a more accurate differential diagnosis.

  5. Utility of susceptibility-weighted MRI in differentiating Parkinson's disease and atypical parkinsonism

    International Nuclear Information System (INIS)

    Gupta, Deepak; Saini, Jitender; Kesavadas, Chandrasekharan; Sarma, P.S.; Kishore, Asha

    2010-01-01

    Neuropathological studies report varying patterns of brain mineralization in Parkinson's diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P. Eleven patients with PD, 12 with PSP, 12 with MSA-P, and 11 healthy controls underwent SWI of the brain. Hypointensity of putamen, red nucleus, substantia nigra, and dentate nucleus in all groups were measured using an objective grading scale and scored from 0 to 3. In PSP, hypointensity score of red nucleus was higher than that in MSA-P (p = 0.001) and PD (p = 0.001), and a score of ≥2 differentiated the PSP group from the PD and MSA-P groups. Putaminal hypointensity score was higher in PSP when compared to that in PD (p = 0.003), and a score of ≥2 differentiated PSP from PD groups. SWI hypointensity scores of red nucleus and putamen had an excellent intrarater and interrater correlation. Substantia nigra hypointensity score of the PSP group was higher than that of the MSA-P (p = 0.004) and PD (p = 0.006) groups, but the scores had only a moderate intrarater and interrater correlation. SWI shows different patterns of brain mineralization in clinically diagnosed groups of PD, PSP, and MSA-P and may be considered as an additional MR protocol to help differentiate these conditions. (orig.)

  6. Residual Salivary Secretion Ability May Be a Useful Marker for Differential Diagnosis in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Etsuko Maeshima

    2014-01-01

    Full Text Available Background. We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS. In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases. Materials and Methods. Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group, patients with systemic sclerosis not complicated by SjS (SSc group, and patients with other autoimmune diseases (non-SjS/non-SSc group. Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates. Results. Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups. Conclusion. Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases.

  7. Viroses confundíveis com febre aftosa Viral diseases to be differentiated from foot-and-mouth disease

    Directory of Open Access Journals (Sweden)

    Franklin Riet-Correa

    1996-08-01

    Full Text Available Revisam-se as doenças que devem ser consideradas no diagnóstico diferencial de febre aftosa. Dentre as doenças vesiculares ou erosivas, descrevem-se os principais aspectos relacionados ao diagnóstico da estomatite vesicular, diarréia viral bovina, febre catarral maligna, infecções por herpesvírus bovino 1 e 5, e uma estomatite ulcerativa associada a parvovírus bovino, que ocorreu no Rio Grande do Sul; língua azul, para a qual tem sido detectados anticorpos em bovinos e ovinos do Rio Grande do Sul; mamilite herpética que ocorre em outros Estados do País;peste bovina, que foi diagnosticada e erradicada no Estado de São Paulo em 1921; estomatite popular; e duas doenças exóticas:exantema vesicular e doença vesicular do suíno.Diseases to be considered in the differential diagnosis of foot-and-mouth disease are reviewed. The main aspects relating to the diagnosis of vesicular stomatitis, bovine virus diarrhea, malignant catarrhal fever, bovine herpesvirus 1 and 5, andem ulcerative stomatitis associated with bovine parvovirus are described. Bluetongue, that probably occurs in Rio Grande do Sul because antibodies to the virus have been detected in cattle and sheep; is refered. Bovine ulcerative mammilitis, reported in other Brazilian States, rinderpest, reported and eradicated in the State of São Paulo in 1921, and popular stomatitis are also cited, and so are two exotic diseases: vesicular exanthema and swine vesicular disease.

  8. My belief or yours? Differential theory of mind deficits in frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Le Bouc, Raphaël; Lenfant, Pierre; Delbeuck, Xavier; Ravasi, Laura; Lebert, Florence; Semah, Franck; Pasquier, Florence

    2012-10-01

    Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [(18)F]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind

  9. Differentiation of malignant and degenerative benign bone disease using 99mTc-citrate scintigraphy

    International Nuclear Information System (INIS)

    Guo Rui; Jin Jianhua; Li Sijin; Li Xianfeng; Zhang Xiaojuan; Ren Yuan

    2008-01-01

    Objective: To differentiate malignant and degenerative benign bone disease using 99m Tc- citrate scintigraphy. Methods: Thirty-nine patients (92 lesions) with confirmed malignant bone disease or degenerative benign bone disease were studied, for which the results of 99m Te-methylene diphosphonate( 99m Tc- MDP) scintigraphy were positive. 99m Tc-citrate scintigraphy was performed within a time interval of 2-7 days after 99m Tc-MDP scintigraphy. Visual analysis and semiquantitative analysis were applied. Each lesion was scored as malignant or benign, which was independently verified, using conventional techniques (histopathology, X-ray, CT, MRI and clinical follow up). Results: In visual analysis of 99m Tc-citrate imaging, most malignant lesions (35/48, 72.92%) clearly showed high radioactivity accumulation, while most benign lesions (39/44, 88.64%) had not obviously visible uptake of 99m Tc-citrate. In semiquantitative analysis of 99m Tc- citrate image, malignant lesions demonstrated a higher lesion-to-background radioisotope uptake ratio (RUR) than that of benign degenerative lesions (1.47 ± 0.42 vs. 1.09 ± 0.38, t=2.887, P 99m Tc-MDP in the two groups is of the same (1.96 ± 0.25 vs. 1.87 ± 0.21, t=1.178, P>0.20). Conclusion: 99m Tc- citrate scintigraphy is a promising method to differentiate malignant from benign degenerative lesions seen as areas of increased activity on 99m Tc-MDP bone scintigraphy. (authors)

  10. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

    Science.gov (United States)

    Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

    2017-08-01

    This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  11. Differential diagnosis of white matter diseases in the tropics: An overview

    Directory of Open Access Journals (Sweden)

    Pandit Lekha

    2009-01-01

    Full Text Available In hospitals in the tropics, the availability of magnetic resonance imaging (MRI facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV infection tops the list of infective conditions. Central nervous system (CNS tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke′s encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics.

  12. Finger tapping movements of Parkinson's disease patients automatically rated using nonlinear delay differential equations.

    Science.gov (United States)

    Lainscsek, C; Rowat, P; Schettino, L; Lee, D; Song, D; Letellier, C; Poizner, H

    2012-03-01

    Parkinson's disease is a degenerative condition whose severity is assessed by clinical observations of motor behaviors. These are performed by a neurological specialist through subjective ratings of a variety of movements including 10-s bouts of repetitive finger-tapping movements. We present here an algorithmic rating of these movements which may be beneficial for uniformly assessing the progression of the disease. Finger-tapping movements were digitally recorded from Parkinson's patients and controls, obtaining one time series for every 10 s bout. A nonlinear delay differential equation, whose structure was selected using a genetic algorithm, was fitted to each time series and its coefficients were used as a six-dimensional numerical descriptor. The algorithm was applied to time-series from two different groups of Parkinson's patients and controls. The algorithmic scores compared favorably with the unified Parkinson's disease rating scale scores, at least when the latter adequately matched with ratings from the Hoehn and Yahr scale. Moreover, when the two sets of mean scores for all patients are compared, there is a strong (r = 0.785) and significant (p<0.0015) correlation between them.

  13. Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Stubbe, Jane; Skov, Vibe; Thiesson, Helle Charlotte

    2018-01-01

    BACKGROUND: Uremia accelerates atherosclerosis but little is known about affected pathways in human vasculature. This study aimed to identify differentially expressed arterial transcripts in patients with chronic kidney disease (CKD) Methods: Global mRNA expression was estimated by microarray...... hybridization in iliac arteries (n=14) from renal transplant recipients and compared with renal arteries from healthy living kidney donors (n=19) in study 1. Study 2 compared non-atherosclerotic internal mammary arteries (IMA) from five patients with elevated plasma creatinine levels and age and gender matched...... controls with normal levels. Western blotting and immunohistochemistry for selected proteins was performed on a subset of study 1 samples. RESULTS: 15 gene transcripts with fold changes (FC)>1.05 were significantly different between the two groups in study 1, with false discovery rates (FDR) of

  14. How to differentiate renal senescence from chronic kidney disease in clinical practice.

    Science.gov (United States)

    Musso, Carlos G; Jauregui, Jose R

    2016-09-01

    Renal aging is frequently confused with chronic nephropathy in clinical practice, since there are some similarities between them, particularly regarding reduced glomerular filtration rate (GFR). However, there are many differences between these two entities which can help any practitioner to distinguish between them, such as: GFR deterioration rate, hematocrit, renal handling of urea, creatinine and some electrolytes, tubular acidification, urinalysis, and renal imaging. Differentiation between renal aging and chronic renal disease is crucial in order to avoid unnecessary medicalization of what is a physiological change associated with the healthy aging process, and the potential harmful consequences of such overdiagnosis. A recently described equation (HUGE), as well as an adequate nephrological evaluation and follow up can help physicians to distinguish both entities.

  15. Differentiating Patients with Parkinson's Disease from Normal Controls Using Gray Matter in the Cerebellum.

    Science.gov (United States)

    Zeng, Ling-Li; Xie, Liang; Shen, Hui; Luo, Zhiguo; Fang, Peng; Hou, Yanan; Tang, Beisha; Wu, Tao; Hu, Dewen

    2017-02-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p cerebellum in the clinical diagnosis of PD.

  16. Five-class differential diagnostics of neurodegenerative diseases using random undersampling boosting

    DEFF Research Database (Denmark)

    Tong, Tong; Ledig, Christian; Guerrero, Ricardo

    2017-01-01

    Differentiating between different types of neurodegenerative diseases is not only crucial in clinical practice when treatment decisions have to be made, but also has a significant potential for the enrichment of clinical trials. The purpose of this study is to develop a classification framework......-wise grading features) and non-imaging features (CSF measures) were extracted for each subject. In clinical practice, the prevalence of different dementia types is imbalanced, posing challenges for learning an effective classification model. Therefore, we propose the use of the RUSBoost algorithm in order...... to train classifiers and to handle the class imbalance training problem. Furthermore, a multi-class feature selection method based on sparsity is integrated into the proposed framework to improve the classification performance. It also provides a way for investigating the importance of different features...

  17. Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease.

    Science.gov (United States)

    Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

    2016-01-01

    Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.

  18. Eco-geographical differentiation among Colombian populations of the Chagas disease vector Triatoma dimidiata (Hemiptera: Reduviidae).

    Science.gov (United States)

    Gómez-Palacio, Andrés; Triana, Omar; Jaramillo-O, Nicolás; Dotson, Ellen M; Marcet, Paula L

    2013-12-01

    Triatoma dimidiata is currently the main vector of Chagas disease in Mexico, most Central American countries and several zones of Ecuador and Colombia. Although this species has been the subject of several recent phylogeographic studies, the relationship among different populations within the species remains unclear. To elucidate the population genetic structure of T. dimidiata in Colombia, we analyzed individuals from distinct geographical locations using the cytochrome c oxidase subunit 1 gene and 7 microsatellite loci. A clear genetic differentiation was observed among specimens from three Colombian eco-geographical regions: Inter Andean Valleys, Caribbean Plains and Sierra Nevada de Santa Marta mountain (SNSM). Additionally, evidence of genetic subdivision was found within the Caribbean Plains region as well as moderate gene flow between the populations from the Caribbean Plains and SNSM regions. The genetic differentiation found among Colombian populations correlates, albeit weakly, with an isolation-by-distance model (IBD). The genetic heterogeneity among Colombian populations correlates with the eco-epidemiological and morphological traits observed in this species across regions within the country. Such genetic and epidemiological diversity should be taken into consideration for the development of vector control strategies and entomological surveillance. Copyright © 2013. Published by Elsevier B.V.

  19. Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

    Science.gov (United States)

    Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

    2016-04-01

    DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

  20. Slow flow and mural thrombus in aortic diseases: Spin-echo MR findings and their differentiation

    International Nuclear Information System (INIS)

    Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    In order to evaluate the ability of spin-echo MR imaging to differentiate slow flow from mural thrombus in aortic diseases, we reviewed the spin-echo MR images of 13 patients with intraaortic thrombus documented by CT (N=11) or aortography (N=2). Six patients had aortic aneurysms and seven had aortic dissections. Intraaortic mural thrombi were accompanied by flow-related intraluminal signal of various pattern and extents in all 13 patients. On 10 gated MR studies, slow flow regions showed ever-echo rephasing phenomenon (N=8), interslice variation of signal intensities of the intraluminal signal (N=7) and flow-related ghost artifact (N=2). However, these MR flow phenomena were obscured on two of three non-gated studies. Seven of 13 intraaortic thrombi remained hyperintense on T2-weighted second-echo images. In these circumstance, a hypointense boundary layer between slow flow and mural thrombus, which was caused by either ' boundary layer dephasing phenomenon' of slow flow or 'paramagnetic T2 shortening' of fresh clot at the edge of mural thrombus, was very useful in discriminating the area of slow flow from that of mural thrombus. Proper interpretation of spin-echo MR images may obviate the need for phase display imaging or gradient-echo imaging in differentiating slow flow and mural thrombus

  1. The disease related deaths due to differentiated thyroid carcinomas treated multidisciplinary, including radioiodine

    International Nuclear Information System (INIS)

    Stefanovic, Lj.; Kermeci, K.; Malesevic, M.; Mihailovic, J.; Srbovan, D.; Popadic, S.

    2002-01-01

    Aim: To analyse the disease related deaths of differentiated thyroid carcinoma (DTC) patients treated multidisciplinary, including radioiodine. Patients and Methods: 364 DTC patients were treated from 1977 to the end of 2000. All patients were operated, treated by radioiodine and by hormonal therapy, external radiotherapy was applied in 22 and chemotherapy in 6 of them. 54 treated patients were lost from the follow-up. The course of disease and outcomes are known in 310 patients, among them 53 patients died. The disease related deaths occurred in 33 (10.6%) patients. Results: Between 33 patients whose deaths were in relation with DTC the disease progression was the cause of deaths in 30 (9.7% of treated) patients (the locoregional disease in 10, distant metastases /M1/ in 17, locoregional disease + M1 in 3 patients). From the late complications of treatment died 3 (1%) patients (all of them were in complete remission to the deaths). The mean survival of these 33 patients from the diagnosis to the end of the life was 6.9 years, median 5.1 years, range 2 months to 23.9 years. The five years survived 54.6% of them, 10 years 21.2% and more than 20 years 3%. M1 had 72.7% of patients (lung and/or bone M1 were present in 91.7% of them), N1 had 69.7% and in 30.3% local tumor was T4. In relation to all treated patients died 14.6% men compared to 9% women (p<0.05), 15.7% of patients 45 years old or older compared to 4.4% of younger then 45 years (p<0.001) and 21.3% of patients with follicular type of DTC compared to 7.3% with papillary type (p<0.001). From all patients without radioiodine accumulation in tumor tissue died 60%. Conclusion: The DTC related deaths were the consequence of M1 and less frequently the result of locoregional disease (T4 and/or N1) in about 1/10 of all treated patients. The deaths as result of the late complications of treatment were exceptional. The deaths were significantly more frequent between males, patients 45 years old or older and patients

  2. Predictive Factors for Differentiating Between Septic Arthritis and Lyme Disease of the Knee in Children.

    Science.gov (United States)

    Baldwin, Keith D; Brusalis, Christopher M; Nduaguba, Afamefuna M; Sankar, Wudbhav N

    2016-05-04

    Differentiating between septic arthritis and Lyme disease of the knee in endemic areas can be challenging and has major implications for patient management. The purpose of this study was to identify a prediction rule to differentiate septic arthritis from Lyme disease in children presenting with knee pain and effusion. We retrospectively reviewed the records of patients younger than 18 years of age with knee effusions who underwent arthrocentesis at our institution from 2005 to 2013. Patients with either septic arthritis (positive joint fluid culture or synovial white blood-cell count of >60,000 white blood cells/mm(3) with negative Lyme titer) or Lyme disease (positive Lyme immunoglobulin G on Western blot analysis) were included. To avoid misclassification bias, undiagnosed knee effusions and joints with both a positive culture and positive Lyme titers were excluded. Historical, clinical, and laboratory data were compared between groups to identify variables for comparison. Binary logistic regression analysis was used to identify independent predictive variables. One hundred and eighty-nine patients were studied: 23 with culture-positive septic arthritis, 26 with culture-negative septic arthritis, and 140 with Lyme disease. Multivariate binary logistic regression identified pain with short arc motion, history of fever reported by the patient or a family member, C-reactive protein of >4 mg/L, and age younger than 2 years as independent predictive factors for septic arthritis. A simpler model was developed that showed that the risk of septic arthritis with none of these factors was 2%, with 1 of these factors was 18%, with 2 of these factors was 45%, with 3 of these factors was 84%, or with all 4 of these factors was 100%. Although septic arthritis of the knee and Lyme monoarthritis share common features that can make them difficult to distinguish clinically, the presence of pain with short arc motion, C-reactive protein of >4.0 mg/L, patient-reported history of

  3. Valvular Heart Disease in Women, Differential Remodeling, and Response to New Therapies.

    Science.gov (United States)

    Chandrasekhar, Jaya; Dangas, George; Mehran, Roxana

    2017-09-11

    In the United States, valvular heart disease (VHD) has a prevalence of 2.5%, most commonly presenting as aortic stenosis (AS) or mitral valve regurgitation (MR) and increasingly observed to be of a degenerative etiology. Women frequently have latent symptoms despite significant disease, and it is therefore pertinent to consider both clinical symptoms and imaging findings for decision-making on treatment. Indeed, significant advances have been made in noninvasive imaging allowing for more accurate diagnosis and disease prognostication. While echo remains the standard diagnostic test, multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) provide complementary information on aortic valve calcification and left ventricular (LV) function, respectively. For any given calcification load or increase in calcification density of the aortic valve, women have greater increase in aortic valve stenosis severity than men; thus, moderate AS in women warrants closer attention. MRI allows identification of different patterns of hypertrophy and remodeling, extent of LV fibrosis, and insights into differential reverse remodeling and clinical outcomes in men and women. In conjunction with surgical treatment, percutaneous technologies are being increasingly used in the management of VHD. Nearly 50% of patients undergoing transcatheter aortic valve replacement (TAVR) are women. In high- or intermediate-risk subjects with significant symptomatic AS, TAVR has been shown to be noninferior to surgical AVR (SAVR). Notably, whereas both treatment strategies are equally effective in men, transfemoral TAVR has been shown to be superior to SAVR resulting in better survival in women. Analogously, few data have examined sex differences with percutaneous MitraClip devices in the treatment of degenerative MR, and men and women appear to have equivalent composite outcomes. Randomized clinical trial data are presently awaited for outcomes in the percutaneous treatment of

  4. Disease susceptibility of the human macula: differential gene transcription in the retinal pigmented epithelium/choroid.

    Science.gov (United States)

    Radeke, Monte J; Peterson, Katie E; Johnson, Lincoln V; Anderson, Don H

    2007-09-01

    The discoveries of gene variants associated with macular diseases have provided valuable insight into their molecular mechanisms, but they have not clarified why the macula is particularly vulnerable to degenerative disease. Its predisposition may be attributable to specialized structural features and/or functional properties of the underlying macular RPE/choroid. To examine the molecular basis for the macula's disease susceptibility, we compared the gene expression profile of the human RPE/choroid in the macula with the profile in the extramacular region using DNA microarrays. Seventy-five candidate genes with differences in macular:extramacular expression levels were identified by microarray analysis, of which 29 were selected for further analysis. Quantitative PCR confirmed that 21 showed statistically significant differences in expression. Five genes were expressed at higher levels in the macula. Two showed significant changes in the macular:extramacular expression ratio; another two exhibited changes in absolute expression level, as a function of age or AMD. Several of the differentially expressed genes have potential relevance to AMD pathobiology. One is an RPE cell growth factor (TFPI2), five are extracellular matrix components (DCN, MYOC, OGN, SMOC2, TFPI2), and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2) and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification of regional differences in gene expression in the RPE/choroid is a first step in clarifying the macula's propensity for degeneration. These findings lay the groundwork for further studies into the roles of the corresponding gene products in the normal, aged, and diseased macula.

  5. Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

    International Nuclear Information System (INIS)

    Wada, Nobuyuki; Rino, Yasushi; Masuda, Munetaka; Ito, Koichi; Sugino, Kiminori; Mimura, Takashi; Nagahama, Mitsuji; Kitagawa, Wataru; Shibuya, Hiroshi; Ohkuwa, Keiko; Nakayama, Hirotaka; Hirakawa, Shohei

    2009-01-01

    To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients

  6. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

    Directory of Open Access Journals (Sweden)

    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  7. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  8. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

    Science.gov (United States)

    Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa

    2012-06-01

    IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

  9. Improvisation and co-expression in explorative digital music systems

    DEFF Research Database (Denmark)

    Hansen, Anne-Marie Skriver

    relationships. The benefit of the digitally networked electronic musical instruments is that particular patterns of co-expression can be found and mediated by the music system (that also contains all individual instruments) in ways that make players aware of their mutual play and perhaps will encourage players...... other when they are given a number of creative restrictions in the sonic/musical material that they interact with. The benefit with digital musical instruments is that non-musicians and novices can get access to limited musical material that they are immediately able to master without any musical...... be developed in future designs. The Wacom® pen tablet, a simple drawing interface, was turned into an array of digital musical instruments in order to investigate the benefit of networked musical instruments in the context of the genre of casual games. Through qualitative and quantitative studies of player...

  10. Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis FlowersW

    NARCIS (Netherlands)

    Ginglinger, J.F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T.G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullman, P.; Verstappen, F.W.A.; Bouwmeester, H.J.

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus

  11. Local coexpression domains of two to four genes in the genome of Arabidopsis

    NARCIS (Netherlands)

    Ren, X.Y.; Fiers, M.W.E.J.; Stiekema, W.J.; Nap, J.P.H.

    2005-01-01

    Expression of genes in eukaryotic genomes is known to cluster, but cluster size is generally loosely defined and highly variable. We have here taken a very strict definition of cluster as sets of physically adjacent genes that are highly coexpressed and form so-called local coexpression domains. The

  12. Anxiety disorders and onset of cardiovascular disease: the differential impact of panic, phobias and worry.

    Science.gov (United States)

    Batelaan, Neeltje M; ten Have, Margreet; van Balkom, Anton J L M; Tuithof, Marlous; de Graaf, Ron

    2014-03-01

    Anxiety has been linked to onset of cardiovascular disease. This study examines the differential impact of types of anxiety (panic, phobia and worry) on 3-year onset of non-fatal cardiovascular disease (CVD). By investigating anxiety disorders as opposed to anxiety symptoms and by using a reliable diagnostic instrument to assess anxiety, limitations of previous studies are considered. 5149 persons at risk for CVD were interviewed using the Composite International Diagnostic Interview. The panic-type included panic disorder and panic attacks; the phobic-type included agoraphobia and social phobia, and the worry-type included generalized anxiety disorder. CVD was self-reported and required treatment or monitoring by a doctor. Analyses were adjusted for sociodemographics, behavioral variables, and comorbid somatic and psychiatric disorders. During follow-up, 62 persons (1.2%) developed CVD. Baseline generalized anxiety disorder was strongly associated with onset of CVD (adjusted OR: 3.39). Further research should replicate findings and focus on biological underpinnings of this association. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. MR volumetric measurement of medial temporal lobe in differentiating Alzheimer disease and subcortical ischemic vascular dementia

    International Nuclear Information System (INIS)

    Wang Liang; Li Kuncheng; Liu Shuliang

    2003-01-01

    Objective: To evaluate the value of measurement of medial temporal structure by MR imaging volumetry in the differential diagnosis for patients with Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD). Methods: Thirty-three probable patients of AD, 33 normal controls, and 17 patients suspected with SIVD had been scanned by MRI, and volumetric measurements of amygdala (AMY), hippocampal formations (HF), entorhinal cortices (EC), parahippocampal gyri (PHG), and temporal horn of lateral ventricle (TH) were done on a serial reconstructed MR images. Results: Both atrophy of HF and dilatation of TH were significant (P<0.05) in SIVD group compared with that in control group. All the measurements with the exception of TH were atrophied significantly (P<0.001) in AD group compared with that in SIVD group and could significantly discriminate the two group. Among these indexes, the left EC provided the best discrimination with the specificity of 82.4%, sensitivity of 87.9%, and accuracy of 86.0%, respectively, and the average accuracy of bilateral EC in discrimination was 85%. Conclusion: The MR imaging volumetric measurements of medial temporal structure could offer useful information in discriminating individuals with AD from that with SIVD. Meanwhile, it should be understood that the AD-type pathological changes could also be induced by cerebrovascular disease

  14. Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease.

    Science.gov (United States)

    Mak, Elijah; Su, Li; Williams, Guy B; Watson, Rosie; Firbank, Michael; Blamire, Andrew; O'Brien, John

    2016-02-01

    Dementia with Lewy bodies (DLB) is characterized by relative preservation of the medial temporal lobe compared with Alzheimer disease (AD). The differential involvement of the hippocampal subfields in both diseases has not been clearly established, however. We aim to investigate hippocampal subfield differences in vivo in a clinical cohort of DLB and AD subjects. 104 participants (35 DLBs, 36 ADs, and 35 healthy comparison [HC] subjects) underwent clinical assessment and 3T T1-weighted imaging. A Bayesian model implemented in Freesurfer was used to automatically segment the hippocampus and its subfields. We also examined associations between hippocampal subfields and tests of memory function. Both the AD and DLB groups demonstrated significant atrophy of the total hippocampus relative to HC but the DLB group was characterized by preservation of the cornu ammonis 1 (CA1), fimbria, and fissure. In contrast, all the hippocampal subfields except the fissure were significantly atrophied in AD compared with both DLB and HC groups. Among DLB subjects, CA1 was correlated with the Recent Memory score of the CAMCOG and Delayed Recall subscores of the HVLT. DLB is characterized by milder hippocampal atrophy that was accompanied by preservation of the CA1. The CA1 was also associated with memory function in DLB. Our findings highlight the promising role of hippocampal subfield volumetry, particularly that of the CA1, as a biomarker for the distinction between AD and DLB. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Evaluation of handwriting kinematics and pressure for differential diagnosis of Parkinson's disease.

    Science.gov (United States)

    Drotár, Peter; Mekyska, Jiří; Rektorová, Irena; Masarová, Lucia; Smékal, Zdeněk; Faundez-Zanuy, Marcos

    2016-02-01

    We present the PaHaW Parkinson's disease handwriting database, consisting of handwriting samples from Parkinson's disease (PD) patients and healthy controls. Our goal is to show that kinematic features and pressure features in handwriting can be used for the differential diagnosis of PD. The database contains records from 37 PD patients and 38 healthy controls performing eight different handwriting tasks. The tasks include drawing an Archimedean spiral, repetitively writing orthographically simple syllables and words, and writing of a sentence. In addition to the conventional kinematic features related to the dynamics of handwriting, we investigated new pressure features based on the pressure exerted on the writing surface. To discriminate between PD patients and healthy subjects, three different classifiers were compared: K-nearest neighbors (K-NN), ensemble AdaBoost classifier, and support vector machines (SVM). For predicting PD based on kinematic and pressure features of handwriting, the best performing model was SVM with classification accuracy of Pacc=81.3% (sensitivity Psen=87.4% and specificity of Pspe=80.9%). When evaluated separately, pressure features proved to be relevant for PD diagnosis, yielding Pacc=82.5% compared to Pacc=75.4% using kinematic features. Experimental results showed that an analysis of kinematic and pressure features during handwriting can help assess subtle characteristics of handwriting and discriminate between PD patients and healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

    Science.gov (United States)

    Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

    2017-09-01

    Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases.

    Science.gov (United States)

    Oliveira, Marcio Sacramento de; Leon, Antônio Ponce de; Mattos, Inês Echenique; Koifman, Sérgio

    2011-09-01

    This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99), PM(10), SO(2), and O(3) levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths from PM(10) to lag 1 was 10.01% (95%CI: 1.81-18.88%) in the total female population and 10.04% (95%CI: 0.90-20.02%) in elderly women. The increase in risk of deaths from PM(10) to lag 9 was 8.25% in the total male population (95%CI: 0.86-16.18%) and 10.80% (95%CI: 2.18-20.15%) in elderly men. For exposure to SO(2) and O(3), the risk was significant in the total male population and the elderly, respectively. The results emphasize the need for further studies, focusing on modification of the effects of air pollution on health.

  18. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases

    Directory of Open Access Journals (Sweden)

    Marcio Sacramento de Oliveira

    2011-09-01

    Full Text Available This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99, PM10, SO2, and O3 levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths from PM10 to lag 1 was 10.01% (95%CI: 1.81-18.88% in the total female population and 10.04% (95%CI: 0.90-20.02% in elderly women. The increase in risk of deaths from PM10 to lag 9 was 8.25% in the total male population (95%CI: 0.86-16.18% and 10.80% (95%CI: 2.18-20.15% in elderly men. For exposure to SO2 and O3, the risk was significant in the total male population and the elderly, respectively. The results emphasize the need for further studies, focusing on modification of the effects of air pollution on health.

  19. Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis.

    Science.gov (United States)

    Kabbani, Toufic A; Vanga, Rohini R; Leffler, Daniel A; Villafuerte-Galvez, Javier; Pallav, Kumar; Hansen, Joshua; Mukherjee, Rupa; Dennis, Melinda; Kelly, Ciaran P

    2014-05-01

    Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (Pdiseases (P=0.002), or nutrient deficiencies (P2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have

  20. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

    Science.gov (United States)

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  1. Patterns of population differentiation and natural selection on the celiac disease background risk network.

    Science.gov (United States)

    Sams, Aaron; Hawks, John

    2013-01-01

    Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

  2. Patterns of population differentiation and natural selection on the celiac disease background risk network.

    Directory of Open Access Journals (Sweden)

    Aaron Sams

    Full Text Available Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

  3. Molecular differentiation and phylogenetic analysis of the Egyptian foot-and-mouth disease virus SAT2.

    Science.gov (United States)

    El-Shehawy, Laila I; Abu-Elnaga, Hany I; Rizk, Sonia A; Abd El-Kreem, Ahmed S; Mohamed, A A; Fawzy, Hossam G

    2014-03-01

    In February 2012, a massive new foot-and-mouth disease (FMD) outbreak struck Egypt. In this work, one-step RT-PCR assays were used for in-house detection and differentiation of foot-and-mouth disease virus (FMDV) in Egypt in this year using pan-serotypic and serotype-targeting sequence primers. FMDV SAT2 was the dominant virus in the examined isolates from the epidemic. The complete VP1 coding regions of two isolates were sequenced. The two isolates had 99.2 % sequence identity to most contemporary Egyptian SAT2 reference viruses, whereas they had 89.7-90.1 % identity to the SAT2/EGY/2/2012 isolate, which was collected from Alexandria, Egypt, and previously sequenced by WRLFMD. Phylogenetic analysis showed that Egypt had one topotype and two lineage of FMDV SAT2 in 2012. The Egyptian and the Palestinian 2012 strains were associated mainly with topotype VII, lineage SAT2/VII/Ghb-12, while the virus isolated from Alexandria Governorate belonged to the SAT2/VII/Alx-12 lineage. Topotype VII also comprised lineages that included strains isolated from Libya in 2012 and 2003. Furthermore, within the same topotype, the Egyptian SAT2/2012 isolates were related to strains from Saudi Arabia, Sudan, Eritrea, Cameroon and Nigeria. Nevertheless, more epidemiological work with neighboring countries is needed to prevent cross-border spread of disease and to reach a precise conclusion about the origin of the 2012 FMDV SAT2 emergency in the Middle East.

  4. Characterization of differentially expressed genes involved in pathways associated with gastric cancer.

    Directory of Open Access Journals (Sweden)

    Hao Li

    Full Text Available To explore the patterns of gene expression in gastric cancer, a total of 26 paired gastric cancer and noncancerous tissues from patients were enrolled for gene expression microarray analyses. Limma methods were applied to analyze the data, and genes were considered to be significantly differentially expressed if the False Discovery Rate (FDR value was 2. Subsequently, Gene Ontology (GO categories were used to analyze the main functions of the differentially expressed genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG database, we found pathways significantly associated with the differential genes. Gene-Act network and co-expression network were built respectively based on the relationships among the genes, proteins and compounds in the database. 2371 mRNAs and 350 lncRNAs considered as significantly differentially expressed genes were selected for the further analysis. The GO categories, pathway analyses and the Gene-Act network showed a consistent result that up-regulated genes were responsible for tumorigenesis, migration, angiogenesis and microenvironment formation, while down-regulated genes were involved in metabolism. These results of this study provide some novel findings on coding RNAs, lncRNAs, pathways and the co-expression network in gastric cancer which will be useful to guide further investigation and target therapy for this disease.

  5. Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

    Science.gov (United States)

    Noyan, Kajsa; Nguyen, Son; Betts, Michael R; Sönnerborg, Anders; Buggert, Marcus

    2018-01-01

    Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared with HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+ HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load, and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared with successfully cART-treated subjects. Our findings suggest that ELCs harbor a "healthy" state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.

  6. Differentiating non-motor symptoms in Parkinson's disease from controls and hemifacial spasm.

    Directory of Open Access Journals (Sweden)

    Ming-Hui Yong

    Full Text Available BACKGROUND AND AIMS: Non-motor symptoms (NMS are important manifestations of Parkinson's disease (PD that reduce patients' health-related quality of life. Some NMS may also be caused by age-related changes, or manifested as a psychological reaction to a chronic neurological condition. This case-control study compared the NMS burden among PD patients, healthy controls and hemifacial spasm (HFS patients. In addition, we determined the NMS that discriminated between PD and non-PD subjects. METHODS: 425 subjects were recruited from a tertiary hospital in Singapore (200 PD patients, 150 healthy controls and 75 HFS patients. NMS burden in subjects was measured using the Non-Motor Symptoms Scale (NMSS. RESULTS: NMSS total score was significantly higher in PD patients (37.9±2.6 compared to healthy controls (11.2±0.9 (p<0.0001 and HFS patients (18.0±2.1 (p<0.0001. In addition, NMSS total score was significantly higher in HFS patients compared to healthy controls (p = 0.003. PD patients experienced a higher NMS burden than healthy controls in all domains, and a higher NMS burden than HFS patients in all but attention/memory and urinary domains. NMS burden for HFS and healthy controls differed only in the sleep/fatigue and urinary domains. Using stepwise logistic regression, problems of 'constipation', 'restless legs', 'dribbling saliva', 'altered interest in sex' and 'change in taste or smell' were found to have significant discriminative power in differentiating between PD patients and healthy controls and between PD patients and HFS patients. CONCLUSION: PD patients experienced a greater overall NMS burden compared to both healthy controls and HFS patients. HFS patients demonstrated a higher NMS burden than controls, and some NMS may be common to chronic neurological conditions while others are more specific to PD. Differentiating patients using NMS domains may help refine the clinical management of NMS in PD patients.

  7. Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Julian Caspers

    2017-05-01

    Full Text Available Patients suffering from Parkinson's disease (PD often show impairments in executive function (EF like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF and under their regular dopaminergic medication (ON. We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC and left dorsal premotor region (PMd in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.

  8. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

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    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  9. The Influence of the Coexpression of CD4 and CD8 in Cutaneous Lesions on Prognosis of Mycosis Fungoides: A Preliminary Study

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    Sergio Umberto De Marchi

    2014-01-01

    Full Text Available Background. Although techniques of immunophenotyping have been successful in characterizing the cells in the cutaneous infiltrates of mycosis fungoides little evidence suggests that variations in the phenotypic characterization correlate with prognosis. Objectives. In a preliminary prospective, single-centre, study we correlated the T-cell phenotype in cutaneous biopsies with the progression of the disease to determine whether the coexpression of CD4 and CD8 has an impact on prognosis. Methods. Skin biopsy specimens from 30 newly diagnosed patients were stained with immunoperoxidase techniques to determine their phenotypic characteristics. After a median followup of 42 months patients were divided into two groups with stable and progressive disease. Results. Eighteen patients had the conventional CD4+CD8− T-cell phenotype. Ten patients showed the coexpression of CD4 and CD8 and had a slightly lower rate of progressive disease. Conclusions. The coexpression of CD4 and CD8 in cutaneous lesions is not rare and is associated with a slightly lower rate of progressive disease. Since double positive CD4/CD8 phenotype is rarely reported in mycosis fungoides the presence on conventional immunophenotyping of both CD may be due to a “mixture” of neoplastic cells and inflammatory CD8+ tumor infiltrating lymphocytes. Immunohistochemical study combined with confocal microscopy could clarify this issue.

  10. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn.

    Science.gov (United States)

    Kandulski, Arne; Weigt, Jochen; Caro, Carlos; Jechorek, Doerthe; Wex, Thomas; Malfertheiner, Peter

    2015-06-01

    Mucosal integrity can be assessed in patients with gastroesophageal reflux disease (GERD) by measuring intraluminal baseline impedance (BI). However, it is not clear whether BI is abnormal in patients with functional heartburn (FH), or can be used to distinguish them from patients with GERD. We compared differences in BI between patients with FH vs GERD. We performed a prospective study of 52 patients (16 men; mean age, 55 y; range, 23-78 y) seen at a tertiary university hospital from February 2009 through December 2012. Thirty-five patients had GERD (19 had nonerosive reflux disease [NERD], 16 had erosive reflux disease [ERD]) and 17 had FH. All patients discontinued proton pump inhibitor therapy and then underwent esophagogastroduodenoscopy and multichannel intraluminal impedance and pH monitoring. BI was assessed at 3, 5, 7, 9, 15, and 17 cm proximal to the lower esophageal sphincter in recumbent patients. Biopsy specimens were taken from 3 cm above the gastroesophageal junction; histology analysis was performed to identify and semiquantitatively score (scale, 0-3) dilated intercellular spaces. Baseline impedance in the distal esophagus was significantly lower in patients with NERD or erosive reflux disease (ERD) than FH (P = .0006). At a cut-off value of less than 2100 Ω, BI measurements identified patients with GERD with 78% sensitivity and 71% specificity, with positive and negative predictive values of 75%. Also in the proximal esophagus, reduced levels of BI levels were found only in patients with ERD. There were negative correlations between level of BI and acid exposure time (r = -0.45; P = .0008), number of acidic reflux episodes (r = -0.45; P = .001), and proximal extent (r = -0.40; P = .004). Biopsy specimens from patients with NERD or ERD had significant increases in dilation of intercellular spaces, compared with those from patients with FH; there was an inverse association between dilated intercellular spaces and BI in the distal esophagus

  11. Identification of estrogen receptor dimer selective ligands reveals growth-inhibitory effects on cells that co-express ERα and ERβ.

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    Emily Powell

    Full Text Available Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ.

  12. Early-stage differentiation between presenile Alzheimer’s disease and frontotemporal dementia using arterial spin labeling MRI

    NARCIS (Netherlands)

    R.M.E. Steketee (Rebecca); E.E. Bron (Esther); R. Meijboom (Rozanna); G.C. Houston (Gavin); S. Klein (Stefan); H.J.M.M. Mutsaerts (Henri J. M.); C. Méndez Orellana (Carolina); F.J. De Jong (Frank J.); J.C. van Swieten (John); A. van der Lugt (Aad); M. Smits (Marion)

    2016-01-01

    textabstractObjective: To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer’s disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion

  13. Early-stage differentiation between presenile Alzheimer’s disease and frontotemporal dementia using arterial spin labeling MRI

    NARCIS (Netherlands)

    R.M.E. Steketee (Rebecca); E.E. Bron (Esther); Meijboom, R. (Rozanna); Houston, G.C. (Gavin C.); Klein, S. (Stefan); H.J.M.M. Mutsaerts (Henri J. M.); Orellana, C.P.M. (Carolina P. Mendez); F.J. de Jong (Fransina); J.C. van Swieten (John); A. van der Lugt (Aad); M. Smits (Marion)

    2015-01-01

    textabstractObjective: To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer’s disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion

  14. Clinical Utility of Short Social Cognitive Tests in Early Differentiation of Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Buhl, Christian; Stokholm, Jette; Gade, Anders

    2013-01-01

    Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can be f...

  15. RNA Sequencing and Coexpression Analysis Reveal Key Genes Involved in α-Linolenic Acid Biosynthesis in Perilla frutescens Seed

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    Tianyuan Zhang

    2017-11-01

    Full Text Available Perilla frutescen is used as traditional food and medicine in East Asia. Its seeds contain high levels of α-linolenic acid (ALA, which is important for health, but is scarce in our daily meals. Previous reports on RNA-seq of perilla seed had identified fatty acid (FA and triacylglycerol (TAG synthesis genes, but the underlying mechanism of ALA biosynthesis and its regulation still need to be further explored. So we conducted Illumina RNA-sequencing in seven temporal developmental stages of perilla seeds. Sequencing generated a total of 127 million clean reads, containing 15.88 Gb of valid data. The de novo assembly of sequence reads yielded 64,156 unigenes with an average length of 777 bp. A total of 39,760 unigenes were annotated and 11,693 unigenes were found to be differentially expressed in all samples. According to Kyoto Encyclopedia of Genes and Genomes (KEGG pathway analysis, 486 unigenes were annotated in the “lipid metabolism” pathway. Of these, 150 unigenes were found to be involved in fatty acid (FA biosynthesis and triacylglycerol (TAG assembly in perilla seeds. A coexpression analysis showed that a total of 104 genes were highly coexpressed (r > 0.95. The coexpression network could be divided into two main subnetworks showing over expression in the medium or earlier and late phases, respectively. In order to identify the putative regulatory genes, a transcription factor (TF analysis was performed. This led to the identification of 45 gene families, mainly including the AP2-EREBP, bHLH, MYB, and NAC families, etc. After coexpression analysis of TFs with highly expression of FAD2 and FAD3 genes, 162 TFs were found to be significantly associated with two FAD genes (r > 0.95. Those TFs were predicted to be the key regulatory factors in ALA biosynthesis in perilla seed. The qRT-PCR analysis also verified the relevance of expression pattern between two FAD genes and partial candidate TFs. Although it has been reported that some TFs

  16. Color perception differentiates Alzheimer's Disease (AD) from Vascular Dementia (VaD) patients.

    Science.gov (United States)

    Arnaoutoglou, N A; Arnaoutoglou, M; Nemtsas, P; Costa, V; Baloyannis, S J; Ebmeier, K P

    2017-08-01

    Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between αβ deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003). Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on ΝΙΝDS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: "Ishihara Color Vision Test - 38 Plate." The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used. Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.

  17. Microglial response to Alzheimer's disease is differentially modulated by voluntary wheel running and enriched environments.

    Science.gov (United States)

    Rodríguez, J J; Noristani, H N; Verkhratsky, A

    2015-03-01

    Alzheimer's disease (AD) is an untreatable neurodegenerative disease that deteriorates memory. Increased physical/cognitive activity reduces dementia risk by promoting neuronal and glial response. Although few studies have investigated microglial response in wild-type rodents following exposure to physical/cognitive stimulation, environmental-induced changes of microglia response to AD have been neglected. We investigated effects of running (RUN) and enriched (ENR) environments on numerical density (N v, #/mm(3)) and morphology of microglia in a triple transgenic (3×Tg-AD) mouse model of AD that closely mimics AD pathology in humans. We used immunohistochemical approach to characterise microglial domain by measuring their overall cell surface, volume and somata volume. 3×Tg-AD mice housed in standard control (STD) environment showed significant increase in microglial N v (11.7 %) in CA1 stratum lacunosum moleculare (S.Mol) of the hippocampus at 12 months compared to non-transgenic (non-Tg) animals. Exposure to combined RUN and ENR environments prevented an increase in microglial N v in 3×Tg-AD and reduced microglial numbers to non-Tg control levels. Interestingly, 3×Tg-AD mice housed solely in ENR environment displayed significant decrease in microglial N v in CA1 subfield (9.3 % decrease), stratum oriens (11.5 % decrease) and S.Mol (7.6 % decrease) of the hippocampus compared to 3×Tg-AD mice housed in STD environment. Morphological analysis revealed microglial hypertrophy due to pronounced increase in microglia surface, volume and somata volume (61, 78 and 41 %) in 3×Tg-AD mice housed in RUN (but not in ENR) compared to STD environment. These results indicate that exposure to RUN and ENR environments have differential effects on microglial density and activation-associated changes in microglial morphology.

  18. Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls

    Directory of Open Access Journals (Sweden)

    Zhang Shu-Jun

    2010-03-01

    Full Text Available Abstract Background Colorectal cancer (CRC is often diagnosed at a late stage with concomitant poor prognosis. The hypersensitive analytical technique of proteomics can detect molecular changes before the tumor is palpable. The surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS is a newly-developed technique of evaluating protein separation in recent years. The protein chips have established the expression of tumor protein in the serum specimens and become the newly discovered markers for tumor diagnosis. The objective of this study was to find new markers of the diagnosis among groups of CRC, colorectal benign diseases (CBD and healthy controls. The assay of SELDI-TOF-MS with analytical technique of protein-chip bioinformatics was used to detect the expression of protein mass peaks in the sera of patients or controls. One hundred serum samples, including 52 cases of colorectal cancer, 27 cases of colorectal benign disease, and 21 cases of healthy controls, were examined by SELDI-TOF-MS with WCX2 protein-chips. Results The diagnostic models (I, II and III were setup by analyzed the data and sieved markers using Ciphergen - Protein-Chip-Software 5.1. These models were combined with 3 protein mass peaks to discriminate CRC, CBD, and healthy controls. The accuracy, the sensitivity and the particularity of cross verification of these models are all highly over 80%. Conclusions The SELDI-TOF-MS is a useful tool to help diagnose colorectal cancer, especially during the early stage. However, identification of the significantly differentiated proteins needs further study.

  19. The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

    Science.gov (United States)

    Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

    2015-01-01

    Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

  20. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.

    Science.gov (United States)

    Bouquet, Jerome; Soloski, Mark J; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N; Chiu, Charles Y

    2016-02-12

    Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the "window period" of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the

  1. Co-expression analysis and identification of fecundity-related long non-coding RNAs in sheep ovaries.

    Science.gov (United States)

    Miao, Xiangyang; Luo, Qingmiao; Zhao, Huijing; Qin, Xiaoyu

    2016-12-16

    Small Tail Han sheep, including the FecB B FecB B (Han BB) and FecB + FecB + (Han++) genotypes, and Dorset sheep exhibit different fecundities. To identify novel long non-coding RNAs (lncRNAs) associated with sheep fecundity to better understand their molecular mechanisms, a genome-wide analysis of mRNAs and lncRNAs from Han BB, Han++ and Dorset sheep was performed. After the identification of differentially expressed mRNAs and lncRNAs, 16 significant modules were explored by using weighted gene coexpression network analysis (WGCNA) followed by functional enrichment analysis of the genes and lncRNAs in significant modules. Among these selected modules, the yellow and brown modules were significantly related to sheep fecundity. lncRNAs (e.g., NR0B1, XLOC_041882, and MYH15) in the yellow module were mainly involved in the TGF-β signalling pathway, and NYAP1 and BCORL1 were significantly associated with the oxytocin signalling pathway, which regulates several genes in the coexpression network of the brown module. Overall, we identified several gene modules associated with sheep fecundity, as well as networks consisting of hub genes and lncRNAs that may contribute to sheep prolificacy by regulating the target mRNAs related to the TGF-β and oxytocin signalling pathways. This study provides an alternative strategy for the identification of potential candidate regulatory lncRNAs.

  2. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Breast disease with skin thickening: differential diagnosis with mammography and ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Young Rok; Kim, Hak Hee; Cha, Eun Suk; Park, Hye Seong; Kim, Ki Tae; Shinn, Kyung Sub [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    1999-02-01

    Diffuse skin thickening of the breast is produced by lymphedema usually secondary to obstruction of the axillary lymphatics. On physical examination, the affected breast is, due to increased fluid content, larger, heavier, and of higher overall density. Mammography reveals an increased coarse reticular pattern. Thickening of the skin can have many causes. It may be a result of tumor invasion or a tumor in the dermal lymphatics ; or because of lymphatic congestion through obstruction of lymphatic drainage within the breast, in the axilla, or centrally in the mediastinum. Further causes may be congestive heart failure, benign inflammation, primary skin processes such as psoriasis, or systemic diseases which involve the skin. Mammographic appearance is known to be nonspecific. Ultrasound can demonstrate skin thickening directly, but despite some reports suggesting that the cause of skin thickening can be inferred from the results of ultrasound, this is not usually of practical importance. The purpose of this study is to review the causes of skin thickening of the breast and to use mammography and US to differentiate the causes.

  4. Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort.

    Science.gov (United States)

    Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M; Chui, Helena

    2017-01-01

    The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69-0.88, p < 0.0001). In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. © 2017 S. Karger AG, Basel.

  5. Differentiation of semantic dementia and Alzheimer's disease using the Addenbrooke's Cognitive Examination (ACE).

    Science.gov (United States)

    Davies, R Rhys; Dawson, Kate; Mioshi, Eneida; Erzinçlioğlu, Sharon; Hodges, John R

    2008-04-01

    The Addenbrooke's Cognitive Examination (ACE) is a simple diagnostic tool bridging the gap between the very brief Mini Mental State Exam (MMSE) and much longer test batteries used by neuropsychologists which has proven extremely popular internationally. We aimed to assess the ability of the ACE to differentiate semantic dementia (SD) from Alzheimer's disease (AD). The ACE was administered to three groups: SD patients (n = 40) and two separate groups of AD patients (n = 40 in each), matched for overall ACE or MMSE score. Significant differences were found between SD and both AD groups for the ACE sub-scores of naming, reading and orientation in time. Discriminant analysis (SD versus AD) led to the formulation of a 'semantic index' (naming plus reading minus scores for serial-7s, orientation in time and drawing). Application of the semantic index to the patient data found values of less than zero to be predictive of SD rather than AD with 88% sensitivity and 90% specificity. Validation analysis in an independent sample of 24 SD and AD patients proved even more favourable. The overall ACE score is known to be a sensitive, and specific, indicator of early neurodegenerative dementia; this study shows that the ACE can also be used to detect SD through application of the semantic index.

  6. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    2011-02-01

    Full Text Available Neurologic Post Treatment Lyme disease (nPTLS and Chronic Fatigue (CFS are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.Pooled cerebrospinal fluid (CSF samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS, coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01. CFS (n = 43 had 2,783 non-redundant proteins, nPTLS (n = 25 contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes.nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

  7. Co-Expression of Neighboring Genes in the Zebrafish (Danio rerio Genome

    Directory of Open Access Journals (Sweden)

    Daryi Wang

    2009-08-01

    Full Text Available Neighboring genes in the eukaryotic genome have a tendency to express concurrently, and the proximity of two adjacent genes is often considered a possible explanation for their co-expression behavior. However, the actual contribution of the physical distance between two genes to their co-expression behavior has yet to be defined. To further investigate this issue, we studied the co-expression of neighboring genes in zebrafish, which has a compact genome and has experienced a whole genome duplication event. Our analysis shows that the proportion of highly co-expressed neighboring pairs (Pearson’s correlation coefficient R>0.7 is low (0.24% ~ 0.67%; however, it is still significantly higher than that of random pairs. In particular, the statistical result implies that the co-expression tendency of neighboring pairs is negatively correlated with their physical distance. Our findings therefore suggest that physical distance may play an important role in the co-expression of neighboring genes. Possible mechanisms related to the neighboring genes’ co-expression are also discussed.

  8. Construction and comparison of gene co-expression networks shows complex plant immune responses

    Directory of Open Access Journals (Sweden)

    Luis Guillermo Leal

    2014-10-01

    Full Text Available Gene co-expression networks (GCNs are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA. Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses.

  9. Co-expression network analysis of duplicate genes in maize (Zea mays L.) reveals no subgenome bias.

    Science.gov (United States)

    Li, Lin; Briskine, Roman; Schaefer, Robert; Schnable, Patrick S; Myers, Chad L; Flagel, Lex E; Springer, Nathan M; Muehlbauer, Gary J

    2016-11-04

    Gene duplication is prevalent in many species and can result in coding and regulatory divergence. Gene duplications can be classified as whole genome duplication (WGD), tandem and inserted (non-syntenic). In maize, WGD resulted in the subgenomes maize1 and maize2, of which maize1 is considered the dominant subgenome. However, the landscape of co-expression network divergence of duplicate genes in maize is still largely uncharacterized. To address the consequence of gene duplication on co-expression network divergence, we developed a gene co-expression network from RNA-seq data derived from 64 different tissues/stages of the maize reference inbred-B73. WGD, tandem and inserted gene duplications exhibited distinct regulatory divergence. Inserted duplicate genes were more likely to be singletons in the co-expression networks, while WGD duplicate genes were likely to be co-expressed with other genes. Tandem duplicate genes were enriched in the co-expression pattern where co-expressed genes were nearly identical for the duplicates in the network. Older gene duplications exhibit more extensive co-expression variation than younger duplications. Overall, non-syntenic genes primarily from inserted duplications show more co-expression divergence. Also, such enlarged co-expression divergence is significantly related to duplication age. Moreover, subgenome dominance was not observed in the co-expression networks - maize1 and maize2 exhibit similar levels of intra subgenome correlations. Intriguingly, the level of inter subgenome co-expression was similar to the level of intra subgenome correlations, and genes from specific subgenomes were not likely to be the enriched in co-expression network modules and the hub genes were not predominantly from any specific subgenomes in maize. Our work provides a comprehensive analysis of maize co-expression network divergence for three different types of gene duplications and identifies potential relationships between duplication types

  10. In-silico gene co-expression network analysis in Paracoccidioides brasiliensis with reference to haloacid dehalogenase superfamily hydrolase gene

    Directory of Open Access Journals (Sweden)

    Raghunath Satpathy

    2015-01-01

    Full Text Available Context: Paracoccidioides brasiliensis, a dimorphic fungus is the causative agent of paracoccidioidomycosis, a disease globally affecting millions of people. The haloacid dehalogenase (HAD superfamily hydrolases enzyme in the fungi, in particular, is known to be responsible in the pathogenesis by adhering to the tissue. Hence, identification of novel drug targets is essential. Aims: In-silico based identification of co-expressed genes along with HAD superfamily hydrolase in P. brasiliensis during the morphogenesis from mycelium to yeast to identify possible genes as drug targets. Materials and Methods: In total, four datasets were retrieved from the NCBI-gene expression omnibus (GEO database, each containing 4340 genes, followed by gene filtration expression of the data set. Further co-expression (CE study was performed individually and then a combination these genes were visualized in the Cytoscape 2. 8.3. Statistical Analysis Used: Mean and standard deviation value of the HAD superfamily hydrolase gene was obtained from the expression data and this value was subsequently used for the CE calculation purpose by selecting specific correlation power and filtering threshold. Results: The 23 genes that were thus obtained are common with respect to the HAD superfamily hydrolase gene. A significant network was selected from the Cytoscape network visualization that contains total 7 genes out of which 5 genes, which do not have significant protein hits, obtained from gene annotation of the expressed sequence tags by BLAST X. For all the protein PSI-BLAST was performed against human genome to find the homology. Conclusions: The gene co-expression network was obtained with respect to HAD superfamily dehalogenase gene in P. Brasiliensis.

  11. Laser Raman detection of platelet as a non-invasive approach for early and differential diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    Chen, P; Wang, X H; Cheng, Y; Peng, J; Shen, A G; Hu, J M; Tian, Q; Shang, X L; Liu, Z C; Yao, X Q; Wang, J Z; Baek, S J; Park, A

    2011-01-01

    Early and differential diagnosis of Alzheimer's disease (AD) is a problem that puzzled many doctors. Reliable markers in easy-assembling samples are of considerable clinical diagnostic value. In this work, laser Raman spectroscopy (LRS) was developed a new method that potentially allows early and differential diagnosis of AD from the platelet sample. Raman spectra of platelets isolated from different ages of AD transgenic mice and non-transgenic controls were collected and analyzed. Multilayer perceptron networks (MLP) classification method was used to classify spectra and establish the diagnostic models. For differential diagnosis, spectra of platelets isolated from AD, Parkinson's disease (PD) and vascular dementia (VD) mice were also discriminated. Two notable spectral differences at 740 and 1654 cm -1 were revealed in the mean spectrum of platelets isolated from AD transgenic mice and the controls. MLP displayed a powerful ability in the classifying of early, advanced AD and the control group, and in differential diagnosis of PD and advanced AD, as well as VD and advanced AD. The results suggest that platelet detecting by LRS coupled with MLP analysis appears to be an easy and accurate method for early and differential diagnosis of AD. This technique could be rapidly promoted from laboratory to the hospital

  12. Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer's disease and normal ageing.

    Directory of Open Access Journals (Sweden)

    Min-Chien Tu

    Full Text Available To describe and compare diffusion tensor imaging (DTI parameters between patients with subcortical ischemic vascular disease (SIVD and Alzheimer's disease (AD diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA and mean diffusivity (MD values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB compared to those with AD (p < 0.05 in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05, while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05. Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001 with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value

  13. Differential diagnosis between Parkinson's disease and essential tremor using the smartphone's accelerometer.

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    Sergi Barrantes

    Full Text Available The differential diagnosis between patients with essential tremor (ET and those with Parkinson's disease (PD whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis.The study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD, who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients.We could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy. Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD.Based on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable.

  14. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

    2004-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  15. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Lu, Mei

    2006-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  16. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

    2015-01-01

    Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  17. An automated classification system for the differentiation of obstructive lung diseases based on the textural analysis of HRCT images

    International Nuclear Information System (INIS)

    Park, Seong Hoon; Seo, Joon Beom; Kim, Nam Kug; Lee, Young Kyung; Kim, Song Soo; Chae, Eun Jin; Lee, June Goo

    2007-01-01

    To develop an automated classification system for the differentiation of obstructive lung diseases based on the textural analysis of HRCT images, and to evaluate the accuracy and usefulness of the system. For textural analysis, histogram features, gradient features, run length encoding, and a co-occurrence matrix were employed. A Bayesian classifier was used for automated classification. The images (image number n = 256) were selected from the HRCT images obtained from 17 healthy subjects (n = 67), 26 patients with bronchiolitis obliterans (n = 70), 28 patients with mild centrilobular emphysema (n = 65), and 21 patients with panlobular emphysema or severe centrilobular emphysema (n = 63). An five-fold cross-validation method was used to assess the performance of the system. Class-specific sensitivities were analyzed and the overall accuracy of the system was assessed with kappa statistics. The sensitivity of the system for each class was as follows: normal lung 84.9%, bronchiolitis obliterans 83.8%, mild centrilobular emphysema 77.0%, and panlobular emphysema or severe centrilobular emphysema 95.8%. The overall performance for differentiating each disease and the normal lung was satisfactory with a kappa value of 0.779. An automated classification system for the differentiation between obstructive lung diseases based on the textural analysis of HRCT images was developed. The proposed system discriminates well between the various obstructive lung diseases and the normal lung

  18. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  19. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

    Science.gov (United States)

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

  20. Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes

    DEFF Research Database (Denmark)

    Min, Josine L; Nicholson, George; Halgrimsdottir, Ingileif

    2012-01-01

    Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue...... and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P100,000 individuals; rs10282458, affecting expression of RARRES2...... and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations....

  1. Weighted gene co-expression network analysis reveals potential genes involved in early metamorphosis process in sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Li, Yongxin; Kikuchi, Mani; Li, Xueyan; Gao, Qionghua; Xiong, Zijun; Ren, Yandong; Zhao, Ruoping; Mao, Bingyu; Kondo, Mariko; Irie, Naoki; Wang, Wen

    2018-01-01

    Sea cucumbers, one main class of Echinoderms, have a very fast and drastic metamorphosis process during their development. However, the molecular basis under this process remains largely unknown. Here we systematically examined the gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus) for the first time by RNA sequencing across 16 developmental time points from fertilized egg to juvenile stage. Based on the weighted gene co-expression network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was highly expressed and correlated with the early metamorphosis process from late auricularia to doliolaria larva. Furthermore, gene enrichment and differentially expressed gene analysis identified several genes in the module that may play key roles in the metamorphosis process. Our results not only provide a molecular basis for experimentally studying the development and morphological complexity of sea cucumber, but also lay a foundation for improving its emergence rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

    Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

  3. Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle Development.

    Science.gov (United States)

    Zhao, Yunxia; Hou, Ye; Zhao, Changzhi; Liu, Fei; Luan, Yu; Jing, Lu; Li, Xinyun; Zhu, Mengjin; Zhao, Shuhong

    2016-01-01

    Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified in various species. However, the biological functions of cis-NATs are largely unknown. In this study, we investigated the transcriptional characteristics and functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their sense genes at the transcriptional level, and approximately 80% of them were co-expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis-NATs were identified during muscle development. Function annotation showed that the cis-NATs participated in muscle development mainly by co-expressing with genes involved in energy metabolic pathways, including citrate cycle (TCA cycle), glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover, these cis-NATs and their sense genes abruptly increased at the transition from the late fetal stages to the early postnatal stages and then decreased along with muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were identified and determined to be mainly co-expressed with their sense genes. The co-expressed cis-NATs and their sense gene were primarily related to energy metabolic pathways during muscle development in pigs. Our results offered novel evidence on the roles of cis-NATs during the muscle development of pigs.

  4. Guidance for RNA-seq co-expression network construction and analysis: safety in numbers.

    Science.gov (United States)

    Ballouz, S; Verleyen, W; Gillis, J

    2015-07-01

    RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks. We examine RNA-seq co-expression data generated from 1970 RNA-seq samples using a Guilt-By-Association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were >20 samples with read depth >10 M per sample. While the aggregate network constructed shows good performance (area under the receiver operator characteristic curve ∼0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples are required to obtain 'gold-standard' co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology. jgillis@cshl.edu or sballouz@cshl.edu Networks are available at: http://gillislab.labsites.cshl.edu/supplements/rna-seq-networks/ and 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.

  5. Application of 18F-FDG PET for the diagnosis and differential diagnosis of Alzheimer's disease and Lewy body dementia

    International Nuclear Information System (INIS)

    Klisarova, A.; Bochev, P.; Deleva, N.; Dimitrov, I.; Ivanov, B.

    2010-01-01

    Alzheimer's disease and Lewy body dementia are the two most frequent disorders among degenerative dementias. Their clinical identification and differential diagnosis are often difficult in the early stages when, on the other hand treatment is most effective. FDG-PET assessment of region brain metabolism is a proven method and its application demented patients ensures a higher diagnostic accuracy even at the preclinical stage. It helps resolving cases with difficult differential diagnosis as well. In this paper we discuss the application of the method in Alzheimer's disease and Lev body dementia; we present typical cases of both disorder which were assessed by FDG-PET for the first time in Bulgaria highlighting the methodology and the characteristic imaging findings

  6. MIDBRAIN CATECHOLAMINERGIC NEURONS CO-EXPRESS α-SYNUCLEIN AND TAU IN PROGRESSIVE SUPRANUCLEAR PALSY

    Directory of Open Access Journals (Sweden)

    María Elena eErro Aguirre

    2015-03-01

    Full Text Available Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP.Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients’ clinical symptoms were retrospectively recorded. Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs were only found in two PSP cases (8% that fulfilled the clinical subtype of PSP known as Richardson’s syndrome (RS. LBs were present in the locus ceruleus, substantia nigra pars compacta, basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson’s disease. Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase-positive neurons of the locus ceruleus and substantia nigra pars compacta.Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as ‘misfolded protein diseases’.

  7. Application of Weighted Gene Co-expression Network Analysis for Data from Paired Design.

    Science.gov (United States)

    Li, Jianqiang; Zhou, Doudou; Qiu, Weiliang; Shi, Yuliang; Yang, Ji-Jiang; Chen, Shi; Wang, Qing; Pan, Hui

    2018-01-12

    Investigating how genes jointly affect complex human diseases is important, yet challenging. The network approach (e.g., weighted gene co-expression network analysis (WGCNA)) is a powerful tool. However, genomic data usually contain substantial batch effects, which could mask true genomic signals. Paired design is a powerful tool that can reduce batch effects. However, it is currently unclear how to appropriately apply WGCNA to genomic data from paired design. In this paper, we modified the current WGCNA pipeline to analyse high-throughput genomic data from paired design. We illustrated the modified WGCNA pipeline by analysing the miRNA dataset provided by Shiah et al. (2014), which contains forty oral squamous cell carcinoma (OSCC) specimens and their matched non-tumourous epithelial counterparts. OSCC is the sixth most common cancer worldwide. The modified WGCNA pipeline identified two sets of novel miRNAs associated with OSCC, in addition to the existing miRNAs reported by Shiah et al. (2014). Thus, this work will be of great interest to readers of various scientific disciplines, in particular, genetic and genomic scientists as well as medical scientists working on cancer.

  8. Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma.

    Science.gov (United States)

    Bahmad, Hisham; Hadadeh, Ola; Chamaa, Farah; Cheaito, Katia; Darwish, Batoul; Makkawi, Ahmad-Kareem; Abou-Kheir, Wassim

    2017-01-01

    With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro . The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.

  9. Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2.

    Directory of Open Access Journals (Sweden)

    Melissa L Perreault

    Full Text Available In basal ganglia a significant subset of GABAergic medium spiny neurons (MSNs coexpress D1 and D2 receptors (D1R and D2R along with the neuropeptides dynorphin (DYN and enkephalin (ENK. These coexpressing neurons have been recently shown to have a region-specific distribution throughout the mesolimbic and basal ganglia circuits. While the functional relevance of these MSNs remains relatively unexplored, they have been shown to exhibit the unique property of expressing the dopamine D1-D2 receptor heteromer, a novel receptor complex with distinct pharmacology and cell signaling properties. Here we showed that MSNs coexpressing the D1R and D2R also exhibited a dual GABA/glutamate phenotype. Activation of the D1R-D2R heteromer in these neurons resulted in the simultaneous, but differential regulation of proteins involved in GABA and glutamate production or vesicular uptake in the nucleus accumbens (NAc, ventral tegmental area (VTA, caudate putamen and substantia nigra (SN. Additionally, activation of the D1R-D2R heteromer in NAc shell, but not NAc core, differentially altered protein expression in VTA and SN, regions rich in dopamine cell bodies. The identification of a MSN with dual inhibitory and excitatory intrinsic functions provides new insights into the neuroanatomy of the basal ganglia and demonstrates a novel source of glutamate in this circuit. Furthermore, the demonstration of a dopamine receptor complex with the potential to differentially regulate the expression of proteins directly involved in GABAergic inhibitory or glutamatergic excitatory activation in VTA and SN may potentially provide new insights into the regulation of dopamine neuron activity. This could have broad implications in understanding how dysregulation of neurotransmission within basal ganglia contributes to dopamine neuronal dysfunction.

  10. Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Chaoqun Li

    2018-01-01

    Full Text Available Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice. Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to

  11. Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus.

    Science.gov (United States)

    Li, Chaoqun; Cao, Feifei; Li, Shengli; Huang, Shenglin; Li, Wei; Abumaria, Nashat

    2017-01-01

    Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice). Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to stress

  12. Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves' Disease and Painless Thyroiditis.

    Science.gov (United States)

    Abdel Razek, Ahmed Abdel Khalek; Abd Allah, Sieza Samir; El-Said, Amr Abd El-Hamid

    2017-01-01

    To assess the role of diffusion-weighted MR imaging in differentiation between Graves' disease and painless thyroiditis. A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. There was a significant difference in the ADC value of the thyroid gland between patients and the control group ( P =0.001). The mean ADC value of the thyroid gland in Graves' disease was 2.03±0.28×10 -3 mm 2 /sec, and in patients with painless thyroiditis 1.46±0.22×10 -3 mm 2 /sec, respectively. There was a significant difference in the ADC values between Graves' disease and painless thyroiditis ( P =0.001). When the ADC value of 1.45×10 -3 mm 2 /sec was used as a threshold value for differentiating Graves' disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake ( r =0.57, P =0.001 and r =0.74, P =0.001, respectively). We concluded that ADC values of the thyroid gland can be used to differentiate Graves' disease from painless thyroiditis in patients with untreated thyrotoxicosis.

  13. Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves’ Disease and Painless Thyroiditis

    Science.gov (United States)

    Abdel Razek, Ahmed Abdel Khalek; El-Said, Amr Abd El-hamid

    2017-01-01

    Summary Background To assess the role of diffusion-weighted MR imaging in differentiation between Graves’ disease and painless thyroiditis. Material/Methods A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. Results There was a significant difference in the ADC value of the thyroid gland between patients and the control group (P=0.001). The mean ADC value of the thyroid gland in Graves’ disease was 2.03±0.28×10–3 mm2/sec, and in patients with painless thyroiditis 1.46±0.22×10–3 mm2/sec, respectively. There was a significant difference in the ADC values between Graves’ disease and painless thyroiditis (P=0.001). When the ADC value of 1.45×10–3 mm2/sec was used as a threshold value for differentiating Graves’ disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake (r=0.57, P=0.001 and r=0.74, P=0.001, respectively). Conclusions We concluded that ADC values of the thyroid gland can be used to differentiate Graves’ disease from painless thyroiditis in patients with untreated thyrotoxicosis. PMID:29662585

  14. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

    Science.gov (United States)

    Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

    2013-09-01

    Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

  15. Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

    Science.gov (United States)

    Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

  16. The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model.

    Science.gov (United States)

    Zhang, Junrong; An, Shengshu; Hu, Wenji; Teng, Meiyu; Wang, Xue; Qu, Yidi; Liu, Yang; Yuan, Ye; Wang, Di

    2016-11-01

    Hericium erinaceus , an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl₃ combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca 2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.

  17. Elucidating gene function and function evolution through comparison of co-expression networks in plants

    Directory of Open Access Journals (Sweden)

    Marek eMutwil

    2014-08-01

    Full Text Available The analysis of gene expression data has shown that transcriptionally coordinated (co-expressed genes are often functionally related, enabling scientists to use expression data in gene function prediction. This Focused Review discusses our original paper (Large-scale co-expression approach to dissect secondary cell wall formation across plant species, Frontiers in Plant Science 2:23. In this paper we applied cross-species analysis to co-expression networks of genes involved in cellulose biosynthesis. We show that the co-expression networks from different species are highly similar, indicating that whole biological pathways are conserved across species. This finding has two important implications. First, the analysis can transfer gene function annotation from well-studied plants, such as Arabidopsis, to other, uncharacterized plant species. As the analysis finds genes that have similar sequence and similar expression pattern across different organisms, functionally equivalent genes can be identified. Second, since co-expression analyses are often noisy, a comparative analysis should have higher performance, as parts of co-expression networks that are conserved are more likely to be functionally relevant. In this Focused Review, we outline the comparative analysis done in the original paper and comment on the recent advances and approaches that allow comparative analyses of co-function networks. We hypothesize that, in comparison to simple co-expression analysis, comparative analysis would yield more accurate gene function predictions. Finally, by combining comparative analysis with genomic information of green plants, we propose a possible composition of cellulose biosynthesis machinery during earlier stages of plant evolution.

  18. Three Dimensional Human Neuro-Spheroid Model of Alzheimer’s Disease Based on Differentiated Induced Pluripotent Stem Cells

    Science.gov (United States)

    Lee, Han-Kyu; Velazquez Sanchez, Clara; Chen, Mei; Morin, Peter J.; Wells, John M.; Hanlon, Eugene B.

    2016-01-01

    The testing of candidate drugs to slow progression of Alzheimer’s disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status. To block the generation of pathologic amyloid β peptides (Aβ), the 3D-differentiated AD neurons were treated with inhibitors targeting β-secretase (BACE1) and γ-secretases. As predicted, both BACE1 and γ-secretase inhibitors dramatically decreased Aβ generation in iPSC-derived neural cells derived from all five AD patients, under standard two-dimensional (2D) differentiation conditions. However, BACE1 and γ-secretase inhibitors showed less potency in decreasing Aβ levels in neural cells differentiated under 3D culture conditions. Interestingly, in a single subject AD1, we found that BACE1 inhibitor treatment was not able to significantly reduce Aβ42 levels. To investigate underlying molecular mechanisms, we performed proteomic analysis of 3D AD human neuronal cultures including AD1. Proteomic analysis revealed specific reduction of several proteins that might contribute to a poor inhibition of BACE1 in subject AD1. To our knowledge, this is the first iPSC-differentiated 3D neuro-spheroid model derived from AD patients’ blood. Our results demonstrate that our 3D human neuro-spheroid model can be a physiologically relevant and valid model for testing efficacy of AD drug. PMID:27684569

  19. Identifying differential miR and gene consensus patterns in peripheral blood of patients with cardiovascular diseases from literature data.

    Science.gov (United States)

    Šatrauskienė, Agnė; Navickas, Rokas; Laucevičius, Aleksandras; Huber, Heinrich J

    2017-06-30

    Numerous recent studies suggest the potential of circulating MicroRNAs (miRs) in peripheral blood samples as diagnostic or prognostic markers for coronary artery disease (CAD), acute coronary syndrome (ACS) and heart failure (HF). However, literature often remains inconclusive regarding as to which markers are most indicative for which of the above diseases. This shortcoming is mainly due to the lack of a systematic analyses and absence of information on the functional pathophysiological role of these miRs and their target genes. We here provide an-easy-to-use scoring approach to investigate the likelihood of regulation of several miRs and their target genes from literature by identifying consensus patterns of regulation. We therefore have screened over 1000 articles that study mRNA markers in cardiovascular and metabolic diseases, and devised a scoring algorithm to identify consensus means for miRs and genes regulation across several studies. We then aimed to identify differential markers between CAD, ACS and HF. We first identified miRs (miR-122, -126, -223, -138 and -370) as commonly regulated within a group of metabolic disease, while investigating cardiac-related pathologies (CAD, ACS, HF) revealed a decisive role of miR-1, -499, -208b, and -133a. Looking at differential markers between cardiovascular disease revealed miR-1, miR-208a and miR-133a to distinguish ACS and CAD to HF. Relating differentially expressed miRs to their putative gene targets using MirTarBase, we further identified HCN2/4 and LASP1 as potential markers of CAD and ACS, but not in HF. Likewise, BLC-2 was found oppositely regulated between CAD and HF. Interestingly, while studying overlap in target genes between CAD, ACS and HF only revealed little similarities, mapping these genes to gene ontology terms revealed a surprising similarity between CAD and ACS compared to HF. We conclude that our analysis using gene and miR scores allows the extraction of meaningful markers and the elucidation

  20. From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

    Science.gov (United States)

    Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

    2017-12-01

    The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

  1. Neurocognitive differential diagnosis of dementing diseases: Alzheimer's Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder.

    Science.gov (United States)

    Braaten, Alyssa J; Parsons, Thomas D; McCue, Robert; Sellers, Alfred; Burns, William J

    2006-11-01

    Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.

  2. Early-stage differentiation between presenile Alzheimer's disease and frontotemporal dementia using arterial spin labeling MRI

    Energy Technology Data Exchange (ETDEWEB)

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Lugt, Aad van der; Smits, Marion [Erasmus MC - University Medical Center, Department of Radiology, PO Box 2040, Rotterdam (Netherlands); Bron, Esther E.; Klein, Stefan [Erasmus MC - University Medical Center, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, PO Box 2040, Rotterdam (Netherlands); Houston, Gavin C. [GE Healthcare, Hatfield (United Kingdom); Mutsaerts, Henri J.M.M. [Academic Medical Center, Department of Radiology, PO Box 22660, Amsterdam (Netherlands); Mendez Orellana, Carolina P. [Erasmus MC - University Medical Center, Department of Radiology, PO Box 2040, Rotterdam (Netherlands); Erasmus MC - University Medical Center, Department of Neurology, PO Box 2040, Rotterdam (Netherlands); Jong, Frank Jan de; Swieten, John C. van [Erasmus MC - University Medical Center, Department of Neurology, PO Box 2040, Rotterdam (Netherlands)

    2016-01-15

    To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer's disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion changes. Thirteen AD and 19 FTD patients, and 25 age-matched older and 22 younger controls underwent 3D pseudo-continuous ASL-MRI at 3 T. Gray matter (GM) volume and cerebral blood flow (CBF), corrected for partial volume effects, were quantified in the entire supratentorial cortex and in 10 GM regions. Sensitivity, specificity and diagnostic performance were evaluated in regions showing significant CBF differences between patient groups or between patients and older controls. AD compared with FTD patients had hypoperfusion in the posterior cingulate cortex, differentiating these with a diagnostic performance of 74 %. Compared to older controls, FTD patients showed hypoperfusion in the anterior cingulate cortex, whereas AD patients showed a more widespread regional hypoperfusion as well as atrophy. Regional atrophy was not different between AD and FTD. Diagnostic performance of ASL to differentiate AD or FTD from controls was good (78-85 %). Older controls showed global hypoperfusion compared to young controls. ASL-MRI contributes to early diagnosis of and differentiation between presenile AD and FTD. (orig.)

  3. Early-stage differentiation between presenile Alzheimer's disease and frontotemporal dementia using arterial spin labeling MRI

    International Nuclear Information System (INIS)

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Lugt, Aad van der; Smits, Marion; Bron, Esther E.; Klein, Stefan; Houston, Gavin C.; Mutsaerts, Henri J.M.M.; Mendez Orellana, Carolina P.; Jong, Frank Jan de; Swieten, John C. van

    2016-01-01

    To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer's disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion changes. Thirteen AD and 19 FTD patients, and 25 age-matched older and 22 younger controls underwent 3D pseudo-continuous ASL-MRI at 3 T. Gray matter (GM) volume and cerebral blood flow (CBF), corrected for partial volume effects, were quantified in the entire supratentorial cortex and in 10 GM regions. Sensitivity, specificity and diagnostic performance were evaluated in regions showing significant CBF differences between patient groups or between patients and older controls. AD compared with FTD patients had hypoperfusion in the posterior cingulate cortex, differentiating these with a diagnostic performance of 74 %. Compared to older controls, FTD patients showed hypoperfusion in the anterior cingulate cortex, whereas AD patients showed a more widespread regional hypoperfusion as well as atrophy. Regional atrophy was not different between AD and FTD. Diagnostic performance of ASL to differentiate AD or FTD from controls was good (78-85 %). Older controls showed global hypoperfusion compared to young controls. ASL-MRI contributes to early diagnosis of and differentiation between presenile AD and FTD. (orig.)

  4. Differential and enhanced response to climate forcing in diarrheal disease due to rotavirus across a megacity of the developing world.

    Science.gov (United States)

    Martinez, Pamela P; King, Aaron A; Yunus, Mohammad; Faruque, A S G; Pascual, Mercedes

    2016-04-12

    The role of climate forcing in the population dynamics of infectious diseases has typically been revealed via retrospective analyses of incidence records aggregated across space and, in particular, over whole cities. Here, we focus on the transmission dynamics of rotavirus, the main diarrheal disease in infants and young children, within the megacity of Dhaka, Bangladesh. We identify two zones, the densely urbanized core and the more rural periphery, that respond differentially to flooding. Moreover, disease seasonality differs substantially between these regions, spanning variation comparable to the variation from tropical to temperate regions. By combining process-based models with an extensive disease surveillance record, we show that the response to climate forcing is mainly seasonal in the core, where a more endemic transmission resulting from an asymptomatic reservoir facilitates the response to the monsoons. The force of infection in this monsoon peak can be an order of magnitude larger than the force of infection in the more epidemic periphery, which exhibits little or no postmonsoon outbreak in a pattern typical of nearby rural areas. A typically smaller peak during the monsoon season nevertheless shows sensitivity to interannual variability in flooding. High human density in the core is one explanation for enhanced transmission during troughs and an associated seasonal monsoon response in this diarrheal disease, which unlike cholera, has not been widely viewed as climate-sensitive. Spatial demographic, socioeconomic, and environmental heterogeneity can create reservoirs of infection and enhance the sensitivity of disease systems to climate forcing, especially in the populated cities of the developing world.

  5. Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

    Directory of Open Access Journals (Sweden)

    Arundhoti Das

    TFs, and their cytokine commitment varied depending on genetic background or priming conditions, without altering pattern of TF co-expression. Thus, the model of mutually antagonistic differentiation programs driven by mutually exclusively expressed T-bet or GATA-3 does not completely explain natural CD4 T cell priming outcomes.

  6. Bilateral Renal Lymphoma a Differential Diagnosis of Policyst Renal Disease. Case Report

    International Nuclear Information System (INIS)

    Poveda S, Cesar A; Rodriguez P, Jose L

    2010-01-01

    A case report of a patient with abdominal pain, diaphoresis and fever of three months duration imaging studies were interpreted as polycystic kidneys. The patient went to another institution, where a different approach led to a kidney biopsy that confirmed renal lymphoma. The case is interesting, by the way it is diagnosed and it is important to note the differential diagnosis.

  7. Differential Epidemiology: IQ, Neuroticism, and Chronic Disease by the 50 U.S. States

    Science.gov (United States)

    Pesta, Bryan J.; Bertsch, Sharon; McDaniel, Michael A.; Mahoney, Christine B.; Poznanski, Peter J.

    2012-01-01

    Current research shows that geo-political units (e.g., the 50 U.S. states) vary meaningfully on psychological dimensions like intelligence (IQ) and neuroticism (N). A new scientific discipline has also emerged, differential epidemiology, focused on how psychological variables affect health. We integrate these areas by reporting large correlations…

  8. Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

    Science.gov (United States)

    Hulsman, Marc; Lelieveldt, Boudewijn P. F.; de Ridder, Jeroen; Reinders, Marcel

    2015-01-01

    The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale). PMID:25965262

  9. Global similarity and local divergence in human and mouse gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-09-01

    Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

  10. Analysis of the relationship between coexpression domains and chromatin 3D organization.

    Directory of Open Access Journals (Sweden)

    María E Soler-Oliva

    2017-09-01

    Full Text Available Gene order is not random in eukaryotic chromosomes, and co-regulated genes tend to be clustered. The mechanisms that determine co-regulation of large regions of the genome and its connection with chromatin three-dimensional (3D organization are still unclear however. Here we have adapted a recently described method for identifying chromatin topologically associating domains (TADs to identify coexpression domains (which we term "CODs". Using human normal breast and breast cancer RNA-seq data, we have identified approximately 500 CODs. CODs in the normal and breast cancer genomes share similar characteristics but differ in their gene composition. COD genes have a greater tendency to be coexpressed with genes that reside in other CODs than with non-COD genes. Such inter-COD coexpression is maintained over large chromosomal distances in the normal genome but is partially lost in the cancer genome. Analyzing the relationship between CODs and chromatin 3D organization using Hi-C contact data, we find that CODs do not correspond to TADs. In fact, intra-TAD gene coexpression is the same as random for most chromosomes. However, the contact profile is similar between gene pairs that reside either in the same COD or in coexpressed CODs. These data indicate that co-regulated genes in the genome present similar patterns of contacts irrespective of the frequency of physical chromatin contacts between them.

  11. ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Saurav Mallik

    2017-12-01

    Full Text Available For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures—weighted rank-based Jaccard and Cosine measures—and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm—RANWAR—was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

  12. ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis.

    Science.gov (United States)

    Mallik, Saurav; Zhao, Zhongming

    2017-12-28

    For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures-weighted rank-based Jaccard and Cosine measures-and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s) through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm-RANWAR-was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

  13. Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

    Science.gov (United States)

    Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

    2016-06-01

    Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Value of analyzing deep gray matter and occipital lobe perfusion to differentiate dementia with Lewy bodies from Alzheimer's disease.

    Science.gov (United States)

    Shimizu, Soichiro; Hanyu, Haruo; Hirao, Kentaro; Sato, Tomohiko; Iwamoto, Toshihiko; Koizumi, Kiyoshi

    2008-12-01

    Dementia with Lewy bodies (DLB) is generally characterized by a decrease in regional cerebral blood flow (rCBF) in the occipital lobe. However, not all patients with DLB have this feature. We explored characteristics of rCBF pattern changes to improve the identification of DLB, in addition to occipital hypoperfusion. The study population comprised 30 patients with probable DLB and 49 patients with probable Alzheimer's disease (AD) who underwent single-photon emission computed tomography. The data were analyzed using Neurological Statistical Image Analysis Software (NEUROSTAT). We established a template of the region of interest (ROI) presenting the parietal lobe, posterior cingulate, striatum, thalamus, and occipital lobe on the standard brain atlas. We then compared the mean Z scores in each ROI between DLB and AD. Moreover, we investigated the value of analyzing relative rCBF changes in both the deep gray matter and occipital lobe in differentiating DLB from AD. The DLB group showed a significant relative rCBF increase in the bilateral striatum and thalamus, and a significant relative rCBF decrease in the bilateral occipital lobe when compared with the AD group. Receiver-operating characteristic analysis revealed that determining the hyperperfusion in the thalamus together with the hypoperfusion in the occipital lobe enabled a more accurate differentiation between DLB and AD than studying individual areas. Studying the relative increase of rCBF in the deep gray matter, and the relative decrease of that in the occipital lobe achieved a high differentiation between DLB and AD. This suggests that determining both an increase and a decrease in rCBF pattern may be important in differentiating between the two diseases.

  15. Regenerative medicine for Parkinson's disease using differentiated nerve cells derived from human buccal fat pad stem cells.

    Science.gov (United States)

    Takahashi, Haruka; Ishikawa, Hiroshi; Tanaka, Akira

    2017-04-01

    The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks. After the morphology of hBFP-ASCs changed to neural-like cells, the medium was replaced with neural maintenance medium. Cells differentiated from hBFP-ASCs showed neuron-like structures and expressed neuron markers (β3-tubulin, neurofilament 200, and microtubule-associated protein 2), an astrocyte marker (glial fibrillary acidic protein), or dopaminergic neuron-related marker (tyrosine hydroxylase). Induced neural cells were transplanted into a 6-hydroxydopamine (6-OHDA)-lesioned rat hemi-parkinsonian model. At 4 weeks after transplantation, 6-OHDA-lesioned rats were subjected to apomorphine-induced rotation analysis. The transplanted cells survived in the brain of rats as dopaminergic neural cells. No tumor formation was found after cell transplantation. We demonstrated differentiation of hBFP-ASCs into neural cells, and that transplantation of these neural cells improved the symptoms of model rats. Our results suggest that neurons differentiated from hBFP-ASCs would be applicable to cell replacement therapy of PD.

  16. Anti-Saccharomyces cerevisiae antibody is not useful to differentiate between Crohn′s disease and intestinal tuberculosis in India

    Directory of Open Access Journals (Sweden)

    Ghoshal U

    2007-01-01

    Full Text Available Context : Clinical, endoscopic, radiological and histological parameters of intestinal tuberculosis (IT and Crohn′s disease (CD are so similar that differentiation between these two diseases, which require different treatment, is difficult. Anti- Saccharomyces cerevisiae antibody (ASCA, which is often present in the sera of patients with CD, may be potentially useful to differentiate CD from IT. Aim : To evaluate the role of enzyme-linked immunosorbent assay test for ASCA in serum in differentiating CD from intestinal tuberculosis. Settings and Design : Prospective case-control study. Materials and Methods: Sixteen patients with IT, 16 CD, 36 UC diagnosed using standard parameters and 12 controls (11 healthy subjects and one with colonic carcinoma were tested for IgG ASCA in serum. Statistical Analysis Used : Categorical variables were analyzed using Chi-square test with Yates′ correction, as applicable. Continuous variables were analyzed using Mann-Whitney U test. Results : Eight of 16 (50% patients with IT, 10 of 16 with CD (62%, nine of 35 with UC (26% and one of 12 controls tested positive for ASCA in serum. Though the frequency of ASCA in serum was comparable among patients with IT and CD (8/16 vs. 10/16, P = ns, IT and UC (8/16 vs. 9/35, P =ns, CD and UC (10/16 vs. 9/35, P =ns, its frequency in CD or IT but not in UC was higher than healthy controls ( P < 0.01. Conclusions : Serum ASCA is unlikely to be useful to differentiate between CD and IT in India.

  17. Value of analyzing deep gray matter and occipital lobe perfusion to differentiate dementia with Lewy bodies from Alzheimer's disease

    International Nuclear Information System (INIS)

    Shimizu, Soichiro; Hanyu, Haruo; Hirao, Kentaro; Sato, Tomohiko; Iwamoto, Toshihiko; Koizumi, Kiyoshi

    2008-01-01

    Dementia with Lewy bodies (DLB) is generally characterized by a decrease in regional cerebral blood flow (rCBF) in the occipital lobe. However, not all patients with DLB have this feature. We explored characteristics of rCBF pattern changes to improve the identification of DLB, in addition to occipital hypoperfusion. The study population comprised 30 patients with probable DLB and 49 patients with probable Alzheimer's disease (AD) who underwent single-photon emission computed tomography. The data were analyzed using Neurological Statistical Image Analysis Soft-ware (NEUROSTAT). We established a template of the region of interest (ROI) presenting the parietal lobe, posterior cingulate, striatum, thalamus, and occipital lobe on the standard brain atlas. We then compared the mean Z scores in each ROI between DLB and AD. Moreover, we investigated the value of analyzing relative rCBF changes in both the deep gray matter and occipital lobe in differentiating DLB from AD. The DLB group showed a significant relative rCBF increase in the bilateral striatum and thalamus, and a significant relative rCBF decrease in the bilateral occipital lobe when compared with the AD group. Receiver-operating characteristic analysis revealed that determining the hyperperfusion in the thalamus together with the hypoperfusion in the occipital lobe enabled a more accurate differentiation between DLB and AD than studying individual areas. Studying the relative increase of rCBF in the deep gray matter, and the relative decrease of that in the occipital lobe achieved a high differentiation between DLB and AD. This suggests that determining both an increase and a decrease in rCBF pattern may be important in differentiating between the two diseases. (author)

  18. Differentiation of Pluripotent Stem Cells to Retinal Pigment Epithelial Cells: An Approach Toward Retinal Degenerative Diseases Treatment

    Directory of Open Access Journals (Sweden)

    Maryam Parvini

    2013-10-01

    Full Text Available Pluripotent stem cells as the cells with a capacity for self-renewal and differentiation into various specificcell types have been highly regarded in regenerative medicine studies. To repair the eye disease damages, thedifferentiation into retinal pigment epithelial cells of pluripotent stem cells has gained great importance inrecent decades because the inappropriate function of these cells is the main cause of degenerative diseases suchas the age-related macular degeneration. Millions of people in the world suffer this disease.To restore the damaged cells and, finally, to improve the vision, numerous studies have been conducted on usingpluripotent stem cells, their differentiation into retinal pigment epithelial cells, and finally, their applicationin cell therapy. Based on this, many researchers have attempted to produce highly efficient retinal pigmentepithelial cells, such that they show a proper function after transplant, along with the host cells. In this reviewarticle, the importance and the role of pigment epithelial cells, as well as, the studies on the in vitro productionof these cells were examined

  19. Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations — Initial experience

    International Nuclear Information System (INIS)

    Bickelhaupt, S.; Froehlich, J.M.; Cattin, R.; Patuto, N.; Tutuian, R.; Wentz, K.U.; Culmann, J.L.; Raible, S.; Bouquet, H.; Bill, U.; Patak, M.A.

    2013-01-01

    active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease

  20. Differential diagnosis of depression and Alzheimer's disease with the Addenbrooke's Cognitive Examination-Revised (ACE-R).

    Science.gov (United States)

    Rotomskis, Augustinas; Margevičiūtė, Ramunė; Germanavičius, Arūnas; Kaubrys, Gintaras; Budrys, Valmantas; Bagdonas, Albinas

    2015-04-17

    One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD). This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group. The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.

  1. HIRSCHSPRUNG'S DISEASE—The Clinical Differentiation and Treatment of Children with Hirschsprung's Disease and Pseudo-Hirschsprung's Disease

    Science.gov (United States)

    Ravitch, Mark M.

    1958-01-01

    Hirschsprung's disease is marked by constipation from the time of birth, with the development, if uncorrected, of a protuberant abdomen and flared costal margins. The rectal ampulla is empty and the abdomen is filled with fecal masses. Pain is not prominent. Flatus is passed in large amounts. Encopresis does not occur. Barium enema shows the characteristic narrowed distal rectal segment and biopsy of the rectum shows absence of the ganglion cells of the myenteric plexus. Treatment is operative resection of the distal narrow segment and a primary anastomosis. Hirschsprung's disease may be mimicked in children with: 1. Psychogenic constipation—pseudo-Hirschsprung's disease. Unlike Hirschsprung's disease, symptoms do not appear at birth, encopresis is common, and the barium enema shows no narrow distal segment. 2. Mental retardation and cerebral defect. 3. Corrected imperforate anus—on the basis of stenosis, imperfect innervation or poor habit training. 4. Cretinism—with severe constipation and intestinal dilatation perhaps the presenting symptoms. Treatment of these four groups of children with severe constipation not due to Hirschsprung's disease is: For Group 1, open discussion with parent and child. Assumption by the physician of full control of the details of treatment, and relegation of parent to the role of the physician's agent in following the prescribed regimen. For Group 2, an enema regimen. Whereas fairly rapid restoration (and then persistence) of normal bowel habit can be expected in Group 1, the basic defects in Group 2 may require indefinite continuation of treatment. For Group 3, regular enema regimen, in the less severe cases—one identical with that used in Group 1, and dilatation of strictures or anoplasty. In Group 4, thyroid hormone therapy relieves the constipation of hypothyroidism and causes reversion of radiographic changes in the colon and rectum. PMID:13561108

  2. Usefulness of acute phase proteins in differentiating between feline infectious peritonitis and other diseases in cats with body cavity effusions.

    Science.gov (United States)

    Hazuchova, Katarina; Held, Susanne; Neiger, Reto

    2017-08-01

    Objectives The aim of this study was to evaluate the measurement of acute phase proteins (APPs) as a diagnostic tool to differentiate between feline infectious peritonitis (FIP) and other diseases in cats with body cavity effusions. Methods Cats with pleural, abdominal or pericardial effusion were prospectively enrolled. Cats were classified as having or not having FIP based on immunohistochemistry (if available) or a sophisticated statistical method using machine learning methodology with concepts from game theory. Cats without FIP were further subdivided into three subgroups: cardiac disease, neoplasia and other diseases. Serum amyloid A (SAA), haptoglobin (Hp) and α 1 -acid glycoprotein (AGP) were measured in serum and effusion, using assays previously validated in cats. Results Serum and effusion samples were available for the measurement of APPs from 88 and 67 cats, respectively. Concentrations of the APPs in serum and effusion were significantly different in cats with and without FIP ( P <0.001 for all three APPs). The best APP to distinguish between cats with and without FIP was AGP in the effusion; a cut-off value of 1550 µg/ml had a sensitivity and specificity of 93% each for diagnosing FIP. Conclusions and relevance AGP, particularly if measured in effusion, was found to be useful in differentiating between FIP and other diseases, while SAA and Hp were not. The concentration of all three APPs in some diseases (eg, septic processes, disseminated neoplasia) was as high as in cats with FIP; therefore, none of these can be recommended as a single diagnostic test for FIP.

  3. Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways

    Directory of Open Access Journals (Sweden)

    Kelly N Holohan

    2013-01-01

    Full Text Available Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer’s disease (AD and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on eight of these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis whereas others are more parallel in their activity (e.g., immune activation and inflammation. A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for mi

  4. Synchronous myeloproliferative and inflammatory disease of the nasal cavity and paranasal sinuses: an interesting differential diagnostic problem.

    Science.gov (United States)

    László, Iván; Gábor, Vass; Zsolt, Bella; László, Tiszlavicz; József, Jóri

    2009-09-01

    The authors present a case of synchronous manifestation of a myeloproliferative--extramedullary plasmocytoma--and a chronic inflammatory disease of the nose and the paranasal sinuses. They emphasise the importance of imaging techniques and immunohistochemistry in the differential diagnosis. They discuss on the basis of published articles the new classification, clinical manifestations, diagnostic and therapeutical approaches of this tumour belonging to the group of monoclonal gammopathies, which originates from an abnormal proliferation of mature B-lymphocytes, and is a rarity in the literature even nowadays.

  5. Quantitative thyroid scintigraphy for the differentiation of Graves' disease and hyperthyroid autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Sahlmann, C.O.; Siefker, U.; Lehmann, K.; Harms, E.; Conrad, M.; Meller, J.

    2004-01-01

    The purpose of this study is the evaluation of the TCTUs in the differentiation between AIT and GD in patients with hyperthyroidism. Methods: We determined the TCTUs in 59 patients with untreated hyperthyroid GD and in 51 patients with AIT who had subclinical or manifest hyperthyroidism without medication. Patients with GD were characterized by the presence of hyperthyroidism, decreased echogenicity of the thyroid, elevation of TSH-receptor autoantibodies (TRAb). AIT was defined by a decreased echogenicity of the thyroid, absence of elevated TSH-receptor autoantibodies (TRAb), autoantibodies against the thyroid peroxidase (anti-TPO) and spontaneous remission or development of subclinical hypothyroidism within 3 months. Results: Thyroid volumes of patients with AIT were significantly lower than those of patients with GD (p 99m TcO 4 - offered rapid and reliable differentiation between hyperthyroid GD and AIT. (orig.)

  6. Incidence of symptomatic salivary disease in patients with differentiated thyroid cancer treated with radioactive iodine

    International Nuclear Information System (INIS)

    Goni E, Ignacio; Selt A, Guillermo Vander; Ruiz A, Catalina; Leon R, Augusto; Solar G, Antonieta; Orellana B, Catalina

    2015-01-01

    Background: The radioactive iodine therapy for differentiated thyroid cancer can produce severe and frequent salivary symptoms, during the treatment or later. Aim: To analyze the incidence, severity and characteristics of the salivary signs and symptoms in these patients. Patients and Method: Retrospective and descriptive anal isis of 106 patients with confirmed diagnosis of differentiated thyroid cancer, treated with surgery and radioactive iodine, that completed a telephonic survey for the evaluation of salivary symptoms. Results: 26 (24.52%) patients presented with salivary symptoms or signs after the radioactive iodine therapy (mean 5 months). The average doses of I 131 was 128,5 mCi. Xerostomy, pain, xeroftalmy, inflammation, sialoadenitis and dysgeusia, were the most frequent clinical symptoms. Conclusions: After radioactive iodine therapy the salivary symptoms and signs incidence is high. We conclude that the indication for this treatment must be selective, but in accordance with the oncological risk of each patient

  7. End-stage renal disease, dialysis, kidney transplantation and their impact on CD4+ -T-cell differentiation.

    Science.gov (United States)

    Schaier, Matthias; Leick, Angele; Uhlmann, Lorenz; Kälble, Florian; Morath, Christian; Eckstein, Volker; Ho, Anthony; Mueller-Tidow, Carsten; Meuer, Stefan; Mahnke, Karsten; Sommerer, Claudia; Zeier, Martin; Steinborn, Andrea

    2018-05-02

    Premature aging of both CD4 + -regulatory- (Tregs) and CD4 + -responder-T-cells (Tresps) in end-stage renal disease (ESRD) patients is expected to affect the success of later kidney transplantation. Both T-cell populations are released from the thymus as inducible co-stimulatory (ICOS + -) and ICOS - -recent thymic emigrant (RTE)-Tregs/Tresps, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS + - and ICOS - -RTE-Tregs/Tresps into ICOS + - or ICOS - -CD31 - -Memory-Tregs/Tresps and examined whether diverging pathways affected the suppressive activity of ICOS + - and ICOS - -Tregs in co-culture with autologous Tresps. Compared to healthy controls, we found an increased differentiation of ICOS + -RTE-Tregs/Tresps and ICOS - -RTE-Tregs via CD31 + -memory-Tregs/Tresps into CD31 - -memory-Tregs/Tresps in ESRD and dialysis patients. In contrast, ICOS - -RTE-Tresps showed an increased differentiation via ICOS - -mature naïve (MN)-Tresps into CD31 - -memory-Tresps. Thereby, the ratio of ICOS + -Tregs/ICOS + -Tresps was not changed, while that of ICOS - -Tregs/ICOS - -Tresps was significantly increased. This differentiation preserved the suppressive activity of both Treg populations in ESRD and partly in dialysis patients. After transplantation, the increased differentiation of ICOS + - and ICOS - -RTE-Tresps proceeded, while that of ICOS + -RTE-Tregs ceased and that of ICOS - -RTE-Tregs switched to an increased differentiation via ICOS - -MN-Tregs. Consequently, the ratios of ICOS + -Tregs/ICOS + -Tresps and of ICOS - -Tregs/ICOS - -Tresps decreased significantly, reducing the suppressive activity of Tregs markedly. Our data reveal that an increased tolerance-inducing differentiation of ICOS + - and ICOS - -Tregs preserves the functional activity of Tregs in ESRD patients, but this cannot be maintained during long-term renal replacement therapy

  8. Decreased health-related quality of life in disease-free survivors of differentiated thyroid cancer in Korea

    Directory of Open Access Journals (Sweden)

    Kim Kwang-Won

    2010-09-01

    Full Text Available Abstract Background Concern regarding the health-related quality of life (HRQOL of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC and to evaluate the important determinants of HRQOL. Methods This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI" and the "hospital anxiety and depression scale" (HADS were used. Data from a large, population based survey of 1,000 people were used as a control. Results The response rate for the questionnaires was 78.9% (316/401. Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social on the EORTC QLQ-C30 compared with controls (P P Conclusions Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.

  9. A co-expression gene network associated with developmental regulation of apple fruit acidity.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Xu, Kenong

    2015-08-01

    Apple fruit acidity, which affects the fruit's overall taste and flavor to a large extent, is primarily determined by the concentration of malic acid. Previous studies demonstrated that the major QTL malic acid (Ma) on chromosome 16 is largely responsible for fruit acidity variations in apple. Recent advances suggested that a natural mutation that gives rise to a premature stop codon in one of the two aluminum-activated malate transporter (ALMT)-like genes (called Ma1) is the genetic causal element underlying Ma. However, the natural mutation does not explain the developmental changes of fruit malate levels in a given genotype. Using RNA-seq data from the fruit of 'Golden Delicious' taken at 14 developmental stages from 1 week after full-bloom (WAF01) to harvest (WAF20), we characterized their transcriptomes in groups of high (12.2 ± 1.6 mg/g fw, WAF03-WAF08), mid (7.4 ± 0.5 mg/g fw, WAF01-WAF02 and WAF10-WAF14) and low (5.4 ± 0.4 mg/g fw, WAF16-WAF20) malate concentrations. Detailed analyses showed that a set of 3,066 genes (including Ma1) were expressed not only differentially (P FDR < 0.05) between the high and low malate groups (or between the early and late developmental stages) but also in significant (P < 0.05) correlation with malate concentrations. The 3,066 genes fell in 648 MapMan (sub-) bins or functional classes, and 19 of them were significantly (P FDR < 0.05) co-enriched or co-suppressed in a malate dependent manner. Network inferring using the 363 genes encompassed in the 19 (sub-) bins, identified a major co-expression network of 239 genes. Since the 239 genes were also differentially expressed between the early (WAF03-WAF08) and late (WAF16-WAF20) developmental stages, the major network was considered to be associated with developmental regulation of apple fruit acidity in 'Golden Delicious'.

  10. Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected Boa Constrictors and Ball Pythons

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Garcia, Valentina E.; Layton, Marylee L.; Hoon-Hanks, Laura L.; Boback, Scott M.; Keel, M. Kevin; Drazenovich, Tracy

    2017-01-01

    ABSTRACT Inclusion body disease (IBD) is an infectious disease originally described in captive snakes. It has traditionally been diagnosed by the presence of large eosinophilic cytoplasmic inclusions and is associated with neurological, gastrointestinal, and lymphoproliferative disorders. Previously, we identified and established a culture system for a novel lineage of arenaviruses isolated from boa constrictors diagnosed with IBD. Although ample circumstantial evidence suggested that these viruses, now known as reptarenaviruses, cause IBD, there has been no formal demonstration of disease causality since their discovery. We therefore conducted a long-term challenge experiment to test the hypothesis that reptarenaviruses cause IBD. We infected boa constrictors and ball pythons by cardiac injection of purified virus. We monitored the progression of viral growth in tissues, blood, and environmental samples. Infection produced dramatically different disease outcomes in snakes of the two species. Ball pythons infected with Golden Gate virus (GoGV) and with another reptarenavirus displayed severe neurological signs within 2 months, and viral replication was detected only in central nervous system tissues. In contrast, GoGV-infected boa constrictors remained free of clinical signs for 2 years, despite high viral loads and the accumulation of large intracellular inclusions in multiple tissues, including the brain. Inflammation was associated with infection in ball pythons but not in boa constrictors. Thus, reptarenavirus infection produces inclusions and inclusion body disease, although inclusions per se are neither necessarily associated with nor required for disease. Although the natural distribution of reptarenaviruses has yet to be described, the different outcomes of infection may reflect differences in geographical origin. IMPORTANCE New DNA sequencing technologies have made it easier than ever to identify the sequences of microorganisms in diseased tissues, i

  11. Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks

    Directory of Open Access Journals (Sweden)

    Kohane Isaac S

    2005-09-01

    Full Text Available Abstract Background Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. Results We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. Conclusion We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing

  12. Gallium scanning in differentiating malignant from benign asbestos-related pleural disease

    International Nuclear Information System (INIS)

    Teirstein, A.S.; Chahinian, P.; Goldsmith, S.J.; Sorek, M.

    1986-01-01

    In order to assess the utility of 67gallium citrate in delineating malignant pleural mesothelioma from benign asbestos-related pleural disease, 49 patients with malignant mesothelioma and 16 with benign asbestos-related pleural disease were studied. Seven patients with malignant mesothelioma had no history of asbestos exposure, while the remaining 58 patients were exposed. Forty-three of the 49 patients (88%) with malignant mesothelioma had a positive 67gallium scan including 36 of the 42 (86%) patients with asbestos exposure and all 7 patients without a history of asbestos exposure. Three of 16 patients (19%) with benign asbestos-related pleural disease had a positive scan. 67Gallium radionuclide imaging is nonspecific but may be valuable in noninvasive monitoring of asbestos-exposed populations, which have a high risk for the late development of benign and/or malignant pleural disease

  13. Differential glucose metabolism in mice and humans affected by McArdle disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

    2016-01-01

    McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated......, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism....... In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle...

  14. X-ray diagnostic sign for the differentiation of neurogenic and primary muscular diseases

    International Nuclear Information System (INIS)

    Palvoelgyi, R.; Gallai, M.

    1981-01-01

    The authors give an account of X-ray examinations of the limb musculature of 70 patients suffering from neurogenic muscular diseases, 42 suffering from primary muscular diseases and 45 suffering from senile degeneration of the muscles. Different degree of damage to different parts of the same muscle could only been observed in one case of neurogenic atrophy (in the postpoliomyelitic states) and in two cases of senile degeneration, while it was found in 11 cases (20%) for the other muscular diseases. In the latter cases the more severe muscle damage, which could be demonstrated radiographically, was always found in the part of the muscle adjacent to a tendon. On the above reasons the authors consider that radiographically demonstrable partial or uneven damage to any particular muscle can be used as a new diagnostical information in distinguishing muscular diseases from neurogenic muscular atrophy. (orig.) [de

  15. [The systemic and differential psychoprophylaxis of vascular brain diseases in the workers of an industrial enterprise].

    Science.gov (United States)

    Andreev, A G

    1994-01-01

    Basing on epidemiological, prospective and clinicopsychological data obtained on 1900 industrial workers of Nizhni Novgorod city, the system of psychoprophylaxis and psychotherapy of cerebrovascular diseases has been developed. The system of psychoprophylaxis was used with consideration of the disease stage and phase, psychic and psychosomatic status in risk groups, in subjects with initial and apparent symptoms of cerebrovascular failure. The psychoprophylactic system proved effective in the conditions of a large industrial enterprise.

  16. Building gene co-expression networks using transcriptomics data for systems biology investigations

    DEFF Research Database (Denmark)

    Kadarmideen, Haja; Watson-Haigh, Nathan S.

    2012-01-01

    Gene co-expression networks (GCN), built using high-throughput gene expression data are fundamental aspects of systems biology. The main aims of this study were to compare two popular approaches to building and analysing GCN. We use real ovine microarray transcriptomics datasets representing four......) is connected within a network. The two GCN construction methods used were, Weighted Gene Co-expression Network Analysis (WGCNA) and Partial Correlation and Information Theory (PCIT) methods. Nodes were ranked based on their connectivity measures in each of the four different networks created by WGCNA and PCIT...... (with > 20000 genes) access to large computer clusters, particularly those with larger amounts of shared memory is recommended....

  17. Differential effectiveness of depression disease management for rural and urban primary care patients.

    Science.gov (United States)

    Adams, Scott J; Xu, Stanley; Dong, Fran; Fortney, John; Rost, Kathryn

    2006-01-01

    Federally qualified health centers across the country are adopting depression disease management programs following federally mandated training; however, little is known about the relative effectiveness of depression disease management in rural versus urban patient populations. To explore whether a depression disease management program has a comparable impact on clinical outcomes over 2 years in patients treated in rural and urban primary care practices and whether the impact is mediated by receiving evidence-based care (antidepressant medication and specialty care counseling). A preplanned secondary analysis was conducted in a consecutively sampled cohort of 479 depressed primary care patients recruited from 12 practices in 10 states across the country participating in the Quality Enhancement for Strategic Teaming study. Depression disease management improved the mental health status of urban patients over 18 months but not rural patients. Effects were not mediated by antidepressant medication or specialty care counseling in urban or rural patients. Depression disease management appears to improve clinical outcomes in urban but not rural patients. Because these programs compete for scarce resources, health care organizations interested in delivering depression disease management to rural populations need to advocate for programs whose clinical effectiveness has been demonstrated for rural residents.

  18. The role of diffusion weighted MR imaging for differentiation between Graves' disease and Hashimoto thyroiditis.

    Science.gov (United States)

    Ozturk, T; Bozgeyik, Z; Ozturk, F; Burakgazi, G; Akyol, M; Coskun, S; Ozkan, Y; Ogur, E

    2015-08-01

    The aim of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DWMRI) for differentation between Graves' disease and Hashimoto's thyroiditis. Fifty patients (27 Graves diseases and 23 Hashimoto thyroiditis) and twenty healthy volunteers were examined using T1, T2 and DWMRI. The patients were diagnosed on the basis of physical findings and the results of thyroid function tests and serological tests. Circular ROIs were positioned on the bilateral thyroid lobes and isthmus. All measurements were repeated three different b values including 100, 600 and 1000 s/mm2 in all cases. ADC (Apparent diffusion coefficient) maps were calculated automatically with the MR system. Mean ADC values were 2.93 × 10-3, 1.97 × 10-3 and 1.62 × 10-3 mm2/s in the healthy volunteers; 3.47 × 10-3, 2.25 × 10-3 and 1.64 × 10-3 mm2/s in Graves' disease; 2.53 × 10-3, 1.76 × 10-3, 1.28 × 10-3 mm2/s in Hashimoto thyroiditis for b100, b600 and b1000, respectively. The ADC values of the Graves diseases were higher than healty volunteers and Hashimoto thyroiditis. ADC values were statistically significant for differentation between Hashimoto thyroiditis and Graves' disease all b values (p Hashimoto thyroiditis and Graves' disease.

  19. Immunohistochemical analysis of IgA expression differentiates IgG4-related disease from plasma cell-type Castleman disease.

    Science.gov (United States)

    Manabe, Akihiro; Igawa, Takuro; Takeuchi, Mai; Gion, Yuka; Yoshino, Tadashi; Sato, Yasuharu

    2017-03-01

    Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P IgG4-RD.

  20. Differentiation of malignant and degenerative benign bone disease using Tc-99m Citrate and Tc-99m MDP scintigraphy

    International Nuclear Information System (INIS)

    Jin, J.; Guo, R.; Li, S.-J.; Ren, Y.; Zhang, C.; Zhang, X.

    2007-01-01

    Full text: For the evaluation of bone metastases in patients (pts) with cancer, 99mTcMDP bone scintigraphy is an important tool, but some limitations exist. One of these is the differential diagnosis of malignant and degenerative benign bone disease. The aim of this study was to differentiate them using 99mTcCitrate and 99mTcMDP scintigraphy. Methods: 39 pts (92 lesions) with known malignant or degenerative benign bone disease were studied. 23 pts had malignant bone disease (48 lesions, group 1), the other 16 pts had degenerative benign bone disease (44 lesions, group2), for which the results of 99mTcMDP scintigraphy were positive. In both groups, 99mTcCitrate scintigraphy was performed within a time interval of 2-7 days after 99mTcMDP scintigraphy (555∼740MBq. static, 3hr, planar or SPECT i m a g e s w h e n r e q u i r e d ) . The 99mTccitrate/99mTcMDP lesion-to-background radioisotope uptake ratio (RUR) was calculated for each lesion. Conventional techniques (histopathology, X-ray, CT, MRI and clinical follow up) were considered to be proof of the presence of bone metastases and degenerative benign bone disease. Results: Uptake of 99mTcMDP in the two groups is the same (1.96±0.25 vs. 1.87±0.21; t=1.178, P>0.20), while in 99mTcCitrate image, malignant lesions demonstrated a higher uptake of lesion activity than that of benign degenerative lesions (1.47±0.42 vs. 1.09±0.38; t=2.887, P<0.01). The mean 99mTccitrate/99mTcMDP RUR in the malignant group was significantly higher than the mean in the benign group (0.78±0.21 vs. 0.54±0.19; t=3.646, P<0.001). Conclusions: The preliminary results of the study confirm the usefulness and feasibility of 99mTcCitrate scintigraphy for differentiating malignant from benign degenerative lesions seen as areas of increased activity on 99mTcMDP bone scintigraphy. (author)

  1. Weighted Gene Co-expression Network Analysis of the Dioscin Rich Medicinal Plant Dioscorea nipponica

    Directory of Open Access Journals (Sweden)

    Wei Sun

    2017-06-01

    Full Text Available Dioscorea contains critically important species which can be used as staple foods or sources of bioactive substances, including Dioscorea nipponica, which has been used to develop highly successful drugs to treat cardiovascular disease. Its major active ingredients are thought to be sterol compounds such as diosgenin, which has been called “medicinal gold” because of its valuable properties. However, reliance on naturally growing plants as a production system limits the potential use of D. nipponica, raising interest in engineering metabolic pathways to enhance the production of secondary metabolites. However, the biosynthetic pathway of diosgenin is still poorly understood, and D. nipponica is poorly characterized at a molecular level, hindering in-depth investigation. In the present work, the RNAs from five organs and seven methyl jasmonate treated D. nipponica rhizomes were sequenced using the Illumina high-throughput sequencing platform, yielding 52 gigabases of data, which were pooled and assembled into a reference transcriptome. Four hundred and eighty two genes were found to be highly expressed in the rhizomes, and these genes are mainly involved in stress response and transcriptional regulation. Based on their expression patterns, 36 genes were selected for further investigation as candidate genes involved in dioscin biosynthesis. Constructing co-expression networks based on significant changes in gene expression revealed 15 gene modules. Of these, four modules with properties correlating to dioscin regulation and biosynthesis, consisting of 4,665 genes in total, were selected for further functional investigation. These results improve our understanding of dioscin biosynthesis in this important medicinal plant and will help guide more intensive investigations.

  2. How to differentiate acute pelvic inflammatory disease from acute appendicitis? A decision tree based on CT findings

    Energy Technology Data Exchange (ETDEWEB)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Taourel, Patrice [Lapeyronie Hospital, Department of Medical Imaging, Montpellier (France); Molinari, Nicolas [UMR 5149 IMAG, CHU, Department of Medical Information and Statistics, Montpellier (France)

    2018-02-15

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. (orig.)

  3. How to differentiate acute pelvic inflammatory disease from acute appendicitis? A decision tree based on CT findings

    International Nuclear Information System (INIS)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Taourel, Patrice; Molinari, Nicolas

    2018-01-01

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. (orig.)

  4. Application of disease-associated differentially expressed genes – Mining for functional candidate genes for mastitis resistance in cattle

    Directory of Open Access Journals (Sweden)

    Schwerin Manfred

    2003-06-01

    Full Text Available Abstract In this study the mRNA differential display method was applied to identify mastitis-associated expressed DNA sequences based on different expression patterns in mammary gland samples of non-infected and infected udder quarters of a cow. In total, 704 different cDNA bands were displayed in both udder samples. Five hundred-and-thirty two bands, (75.6% were differentially displayed. Ninety prominent cDNA bands were isolated, re-amplified, cloned and sequenced resulting in 87 different sequences. Amongst the 19 expressed sequence tags showing a similarity with previously described genes, the majority of these sequences exhibited homology to protein kinase encoding genes (26.3%, to genes involved in the regulation of gene expression (26.3%, to growth and differentiation factor encoding genes (21.0% and to immune response or inflammation marker encoding genes (21.0%. These sequences were shown to have mastitis-associated expression in the udder samples of animals with and without clinical mastitis by quantitative RT-PCR. They were mapped physically using a bovine-hamster somatic cell hybrid panel and a 5000 rad bovine whole genome radiation hybrid panel. According to their localization in QTL regions based on an established integrated marker/gene-map and their disease-associated expression, four genes (AHCY, PRKDC, HNRPU, OSTF1 were suggested as potentially involved in mastitis defense.

  5. Korean Addenbrooke's Cognitive Examination Revised (K-ACER) for differential diagnosis of Alzheimer's disease and subcortical ischemic vascular dementia.

    Science.gov (United States)

    Kwak, Yong Tae; Yang, Youngsoon; Kim, Gyung Whan

    2010-10-01

    Sensitive, specific neuropsychological screening tests, such as the Addenbrooke's Cognitive Examination Revised (ACE-R), are essential for dementia diagnosis. We aimed to validate the use of the Korean version of ACE-R (K-ACER) to differentiate Alzheimer's disease (AD) from subcortical ischemic vascular dementia (SIVD). Standard tests for dementia screening were applied to 156 subjects (84 controls, 30 AD, 42 SIVD), and total and sub-domain scores on the K-ACER, as well as the sub-domain ratio (VLOM), were compared. The reliability of the K-ACER was very good (α-coefficient 0.84), and cut-off score for dementia was determined (cut-off value 78, sensitivity 0.93, specificity 0.95). The likelihood ratio for dementia was calculated as between 78 and 82. At a cut-off of 78, the likelihood of dementia was 18.6:1. Although a comparison of K-ACER scores between AD and SIVD patients revealed significant differences in verbal fluency, language domain and VLOM ratio, sensitivity and specificity for differential diagnosis between AD and SVID proved less accurate. The K-ACER is a rapid, sensitive and specific dementia screening test. Though sub-domains of items may be useful for differentiating between AD and SIVD, sensitivity and specificity is less accurate than dementia screening itself. © 2010 Japan Geriatrics Society.

  6. Accuracy of neuropsychological tests and the Neuropsychiatric Inventory in differential diagnosis between Frontotemporal dementia and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Valéria Santoro Bahia

    Full Text Available Abstract The differential diagnosis between frontotemporal dementia (FTD and Alzheimer's disease (AD is sometimes difficult. Objectives: To verify the accuracy of neuropsychological tests and a behavioral disorders scale in the differential diagnosis between FTLD and AD. Methods: Retrospective data on 12 FTD patients and 12 probable AD patients were analyzed. The scores on neuropsychological tests (MMSE score, reverse digit span, delayed recall for drawings, semantic fluency of animals and the Neuropsychiatric Inventory (NPI in both groups were compared. Results: Both groups had similar performance on neuropsychological tests. All FTD patients and 50% of AD patients had neuropsychiatric abnormalities. The NPI score was 58.0±19.3 for the FTD patients, and 3.6±4.7 for the AD patients (p<0.01. Using a NPI cut-off score of 13, the sensitivity and specificity were 100% in this sample. The four most common neuropsychiatric disturbances in FTD patients were: apathy, aberrant motor behavior, disinhibition and eating abnormalities. Apathy and dysphoria/depression were the most common behavioral symptoms among the AD patients. Conclusions: In this study, NPI was found to be a useful tool for the differential diagnosis between FTD and AD. The neuropsychological tests commonly used in the medical office were unable to distinguish between the two groups.

  7. Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

    Science.gov (United States)

    Morello, Roy; Lee, Brendan

    2002-05-01

    In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

  8. Application of convolutional artificial neural networks to echocardiograms for differentiating congenital heart diseases in a pediatric population

    Science.gov (United States)

    Perrin, Douglas P.; Bueno, Alejandra; Rodriguez, Andrea; Marx, Gerald R.; del Nido, Pedro J.

    2017-03-01

    In this paper we describe a pilot study, where machine learning methods are used to differentiate between congenital heart diseases. Our approach was to apply convolutional neural networks (CNNs) to echocardiographic images from five different pediatric populations: normal, coarctation of the aorta (CoA), hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and single ventricle (SV). We used a single network topology that was trained in a pairwise fashion in order to evaluate the potential to differentiate between patient populations. In total we used 59,151 echo frames drawn from 1,666 clinical sequences. Approximately 80% of the data was used for training, and the remainder for validation. Data was split at sequence boundaries to avoid having related images in the training and validation sets. While training was done with echo images/frames, evaluation was performed for both single frame discrimination as well as sequence discrimination (by majority voting). In total 10 networks were generated and evaluated. Unlike other domains where this network topology has been used, in ultrasound there is low visual variation between classes. This work shows the potential for CNNs to be applied to this low-variation domain of medical imaging for disease discrimination.

  9. Skeletal diseases. Diagnostic clinical radiology and differential diagnostics. 2. rev. and enl. ed.

    International Nuclear Information System (INIS)

    Freyschmidt, J.

    1997-01-01

    The book focuses on the diagnostic evaluation of idiopathic diseases of the skeleton and bone joints, also including the fundamental healing processes of bone fractures, particularly of stress-induced and pathologic fractures. Ample space has been given to the description and imaging of the course of diseases under treatment by up-to-date therapies, as e.g. for ostitis deformans Paget's disease, or skeletal metastases. This second edition of the book incorporates the progress achieved over the last five years in skeletal diagnostics. The advances in this field have been resulting from basic research work, for instance in molecular biology, or from a variety of completed studies relating to clinical medicine, laboratory chemistry, histopathology and radiology of skeletal diseases, and from experience obtained with the diagnostic radiology methods and techniques, with the potentials and constraints of magnetic resonance imaging (MRI) today being more critically assessed than five years ago. MRI is a modality currently meeting with interest in the context of search for additional diagnostic information, new definition of complete pictures of diseases, or false or overinterpretation of diagnostic findings. (orig./MG). 431 figs [de

  10. Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

    Science.gov (United States)

    McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

    2015-01-01

    Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

  11. Multiplex PCR for rapid diagnosis and differentiation of pox and pox-like diseases in dromedary Camels.

    Science.gov (United States)

    Khalafalla, Abdelmalik I; Al-Busada, Khalid A; El-Sabagh, Ibrahim M

    2015-07-07

    Pox and pox-like diseases of camels are a group of exanthematous skin conditions that have become increasingly important economically. Three distinct viruses may cause them: camelpox virus (CMLV), camel parapox virus (CPPV) and camelus dromedary papilloma virus (CdPV). These diseases are often difficult to differentiate based on clinical presentation in disease outbreaks. Molecular methods such as PCR targeting species-specific genes have been developed and used to identify these diseases, but not simultaneously in a single tube. Recently, multiplex PCR has gained reputation as a convenient diagnostic method with cost-and timesaving benefits. In the present communication, we describe the development, optimization and validation of a multiplex PCR assay able to detect simultaneously the genome of the three viruses in one single test allowing for rapid and efficient molecular diagnosis. The assay was developed based on the evaluation and combination of published and new primer sets and was validated with viral genomic DNA extracted from known virus strains (n = 14) and DNA extracted from homogenized clinical skin specimens (n = 86). The assay detects correctly the target pathogens by amplification of targeted genes, even in case of co-infection. The method showed high sensitivity, and the specificity was confirmed by PCR-product sequencing. This assay provide rapid, sensitive and specific method for identifying three important viruses in specimens collected from dromedary camels with varying clinical presentations.

  12. Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

    Directory of Open Access Journals (Sweden)

    Benito Minjarez

    2016-06-01

    Full Text Available Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016 [1].

  13. Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data.

    Science.gov (United States)

    Szigeti, Krisztián; Szabó, Tibor; Korom, Csaba; Czibak, Ilona; Horváth, Ildikó; Veres, Dániel S; Gyöngyi, Zoltán; Karlinger, Kinga; Bergmann, Ralf; Pócsik, Márta; Budán, Ferenc; Máthé, Domokos

    2016-02-11

    Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas.

  14. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

    2016-01-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings...... to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray...... no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus...

  15. Pyrosequencing analysis of the gyrB gene to differentiate bacteria responsible for diarrheal diseases.

    Science.gov (United States)

    Hou, X-L; Cao, Q-Y; Jia, H-Y; Chen, Z

    2008-07-01

    Pathogens causing acute diarrhea include a large variety of species from Enterobacteriaceae and Vibrionaceae. A method based on pyrosequencing was used here to differentiate bacteria commonly associated with diarrhea in China; the method is targeted to a partial amplicon of the gyrB gene, which encodes the B subunit of DNA gyrase. Twenty-eight specific polymorphic positions were identified from sequence alignment of a large sequence dataset and targeted using 17 sequencing primers. Of 95 isolates tested, belonging to 13 species within 7 genera, most could be identified to the species level; O157 type could be differentiated from other E. coli types; Salmonella enterica subsp. enterica could be identified at the serotype level; the genus Shigella, except for S. boydii and S. dysenteriae, could also be identified. All these isolates were also subjected to conventional sequencing of a relatively long ( approximately1.2 kb) region of gyrB DNA; these results confirmed those with pyrosequencing. Twenty-two fecal samples were surveyed, the results of which were concordant with culture-based bacterial identification, and the pathogen detection limit with simulated stool specimens was 10(4) CFU/ml. DNA from different pathogens was also mixed to simulate a case of multibacterial infection, and the generated signals correlated well with the mix ratio. In summary, the gyrB-based pyrosequencing approach proved to have significant reliability and discriminatory power for enteropathogenic bacterial identification and provided a fast and effective method for clinical diagnosis.

  16. Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses

    Directory of Open Access Journals (Sweden)

    Carsten Bergmann

    2018-02-01

    Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is a hepatorenal fibrocystic disorder that is characterized by enlarged kidneys with progressive loss of renal function and biliary duct dilatation and congenital hepatic fibrosis that leads to portal hypertension in some patients. Mutations in the PKHD1 gene are the primary cause of ARPKD; however, the disease is genetically not as homogeneous as long thought and mutations in several other cystogenes can phenocopy ARPKD. The family history usually is negative, both for recessive, but also often for dominant disease genes due to de novo arisen mutations or recessive inheritance of variants in genes that usually follow dominant patterns such as the main ADPKD genes PKD1 and PKD2. Considerable progress has been made in the understanding of polycystic kidney disease (PKD. A reduced dosage of disease proteins leads to the disruption of signaling pathways underlying key mechanisms involved in cellular homeostasis, which may help to explain the accelerated and severe clinical progression of disease course in some PKD patients. A comprehensive knowledge of disease-causing genes is essential for counseling and to avoid genetic misdiagnosis, which is particularly important in the prenatal setting (e.g., preimplantation genetic diagnosis/PGD. For ARPKD, there is a strong demand for early and reliable prenatal diagnosis, which is only feasible by molecular genetic analysis. A clear genetic diagnosis is helpful for many families and improves the clinical management of patients. Unnecessary and invasive measures can be avoided and renal and extrarenal comorbidities early be detected in the clinical course. The increasing number of genes that have to be considered benefit from the advances of next-generation sequencing (NGS which allows simultaneous analysis of a large group of genes in a single test at relatively low cost and has become the mainstay for genetic diagnosis. The broad phenotypic and genetic

  17. Comprehensive analysis of coding-lncRNA gene co-expression network uncovers conserved functional lncRNAs in zebrafish.

    Science.gov (United States)

    Chen, Wen; Zhang, Xuan; Li, Jing; Huang, Shulan; Xiang, Shuanglin; Hu, Xiang; Liu, Changning

    2018-05-09

    Zebrafish is a full-developed model system for studying development processes and human disease. Recent studies of deep sequencing had discovered a large number of long non-coding RNAs (lncRNAs) in zebrafish. However, only few of them had been functionally characterized. Therefore, how to take advantage of the mature zebrafish system to deeply investigate the lncRNAs' function and conservation is really intriguing. We systematically collected and analyzed a series of zebrafish RNA-seq data, then combined them with resources from known database and literatures. As a result, we obtained by far the most complete dataset of zebrafish lncRNAs, containing 13,604 lncRNA genes (21,128 transcripts) in total. Based on that, a co-expression network upon zebrafish coding and lncRNA genes was constructed and analyzed, and used to predict the Gene Ontology (GO) and the KEGG annotation of lncRNA. Meanwhile, we made a conservation analysis on zebrafish lncRNA, identifying 1828 conserved zebrafish lncRNA genes (1890 transcripts) that have their putative mammalian orthologs. We also found that zebrafish lncRNAs play important roles in regulation of the development and function of nervous system; these conserved lncRNAs present a significant sequential and functional conservation, with their mammalian counterparts. By integrative data analysis and construction of coding-lncRNA gene co-expression network, we gained the most comprehensive dataset of zebrafish lncRNAs up to present, as well as their systematic annotations and comprehensive analyses on function and conservation. Our study provides a reliable zebrafish-based platform to deeply explore lncRNA function and mechanism, as well as the lncRNA commonality between zebrafish and human.

  18. Topographical Short-Term Memory Differentiates Alzheimer's Disease From Frontotemporal Lobar Degeneration

    NARCIS (Netherlands)

    Bird, C.M.; Chan, D.; Hartley, T.; Pijnenburg, Y.A.L.; Rossor, M.N.; Burgess, N.

    2010-01-01

    We used a recently developed test of spatial memory-the Four Mountains Test-to investigate the core cognitive processes underpinning topographical disorientation in patients with amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). Performance of these clinical groups was

  19. Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease

    NARCIS (Netherlands)

    Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

    2016-01-01

    Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does,

  20. Dipyridamole Body Surface Potential Mapping: Noninvasive Differentiation of Syndrome X from Coronary Artery Disease

    Czech Academy of Sciences Publication Activity Database

    Boudík, F.; Anger, Z.; Aschermann, M.; Vojáček, J.; Tomečková, Marie

    2002-01-01

    Roč. 35, č. 3 (2002), s. 181-191 ISSN 0022-0736 R&D Projects: GA MZd IZ4038 Keywords : body surface potential mapping * dipyridamole * coronary artery disease * syndrome X Subject RIV: BD - Theory of Information Impact factor: 0.599, year: 2002

  1. Brachial plexus magnetic resonance imaging differentiates between inflammatory neuropathies and does not predict disease course

    NARCIS (Netherlands)

    Jongbloed, BA; Bos, Jeroen W; Rutgers, Dirk; van der Pol, WL; van den Berg, Leonard H

    OBJECTIVE: The main objective of this study was to evaluate the correlation between the distribution of brachial plexus magnetic resonance imaging (MRI) abnormalities and clinical weakness, and to evaluate the value of brachial plexus MRI in predicting disease course and response to treatment in

  2. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

  3. Recent onset neck pain with associated neurological deficit--Pott's disease remains an important differential diagnosis.

    LENUS (Irish Health Repository)

    Bourke, M G

    2010-11-05

    The incidence of spinal tuberculosis is increasing in developed nations. In Ireland, half of all cases seen in the most recent decade for which figures are available were diagnosed in 2005-2007, the three most recent years for which there is complete data. We discuss a patient who presented with neurological complications due to destructive spinal tuberculous disease affecting the sixth cervical vertebra.

  4. Diagnostic accuracy of apparent diffusion coefficient and 123I-metaiodobenzylguanidine for differentiation of multiple system atrophy and Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Atsushi Umemura

    Full Text Available BACKGROUND: It is often hard to differentiate Parkinson's disease (PD and parkinsonian variant of multiple system atrophy (MSA-P, especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively. PURPOSE: We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC test for MSA-P and (123I-metaiodobenzylguanidine (MIBG scintigram for PD, especially in early-stage patients. METHODS: The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson's Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC, sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated. RESULTS: ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD. AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤ 3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis and 47.7% and 92.3% for the MIBG test (PD diagnosis. CONCLUSIONS: Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.

  5. An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features.

    Directory of Open Access Journals (Sweden)

    Muwei Li

    Full Text Available Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI. The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous

  6. Diagnostic accuracy of apparent diffusion coefficient and 123I-metaiodobenzylguanidine for differentiation of multiple system atrophy and Parkinson's disease.

    Science.gov (United States)

    Umemura, Atsushi; Oeda, Tomoko; Hayashi, Ryutaro; Tomita, Satoshi; Kohsaka, Masayuki; Yamamoto, Kenji; Sawada, Hideyuki

    2013-01-01

    It is often hard to differentiate Parkinson's disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively. We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and (123)I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients. The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson's Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated. ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤ 3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis). Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.

  7. Quantitative thyroid scintigraphy for the differentiation of Graves' disease and hyperthyroid autoimmune thyroiditis

    Energy Technology Data Exchange (ETDEWEB)

    Sahlmann, C.O.; Siefker, U.; Lehmann, K.; Harms, E.; Conrad, M.; Meller, J. [Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin

    2004-08-01

    The purpose of this study is the evaluation of the TCTUs in the differentiation between AIT and GD in patients with hyperthyroidism. Methods: We determined the TCTUs in 59 patients with untreated hyperthyroid GD and in 51 patients with AIT who had subclinical or manifest hyperthyroidism without medication. Patients with GD were characterized by the presence of hyperthyroidism, decreased echogenicity of the thyroid, elevation of TSH-receptor autoantibodies (TRAb). AIT was defined by a decreased echogenicity of the thyroid, absence of elevated TSH-receptor autoantibodies (TRAb), autoantibodies against the thyroid peroxidase (anti-TPO) and spontaneous remission or development of subclinical hypothyroidism within 3 months. Results: Thyroid volumes of patients with AIT were significantly lower than those of patients with GD (p<0.05). TRAb levels were significantly higher in GD-patients (median: 19.5 U/ml; range: 15.3-35 U/ml) than in AIT-patients (median: 1.3 U/ml; range: 0-4.1 U/ml). 73% (38/59) of patients with GD had elevated anti-TPO levels. In these patients anti-TPO levels (median: 768 U/l; range: 83-6397 U/l) were not significantly different from anti-TPO levels of patients with AIT (median: 834 U/l; range: 107-8675 U/l; p=0.17). TCTUs values of patients with AIT were significantly lower (p<0.05; median: 0.9%; range: 0.1-3.2%) than those of patients with GD (median: 5.7%; range: 1.9-28.3%). Conclusion: In our patients quantitative thyroid scintigraphy with {sup 99m}TcO{sub 4}{sup -} offered rapid and reliable differentiation between hyperthyroid GD and AIT. (orig.)

  8. Uncovering robust patterns of microRNA co-expression across cancers using Bayesian Relevance Networks.

    Directory of Open Access Journals (Sweden)

    Parameswaran Ramachandran

    Full Text Available Co-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing-with its unique statistical properties-became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available at www.perkinslab.ca.

  9. Uncovering the liver’s role in immunity through RNA co-expression networks

    Czech Academy of Sciences Publication Activity Database

    Harrall, K. K.; Kechris, K. J.; Tabakoff, B.; Hoffman, P.L.; Hines, L. M.; Tsukamoto, H.; Pravenec, Michal; Printz, M.; Saba, L. M.

    2016-01-01

    Roč. 27, 9-10 (2016), s. 469-484 ISSN 0938-8990 R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : RNA coexpression networks * liver * immunity * rat * recombinant inbred strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.509, year: 2016

  10. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, R.; Do, Duy Ngoc

    synthesis. In testis, >80 DE genes were functionally classified by the PANTHER tool to “Gonadotropin releasing hormone receptor” and “Wnt signaling” pathways which play a role in reproductive maturation and proliferation of spermatogonia, respectively. WGCNA was used to build co-expression modules...

  11. Different substrate regimes determine transcriptional profiles and gene co-expression in Methanosarcina barkeri (DSM 800)

    Czech Academy of Sciences Publication Activity Database

    Lin, Qiang; Fang, X.; Ho, A.; Li, J.; Yan, X.; Tu, B.; Li, Ch.; Li, J.; Yao, M.; Li, X.

    2017-01-01

    Roč. 101, č. 19 (2017), s. 7303-7316 ISSN 0175-7598 Institutional support: RVO:60077344 Keywords : Methanosarcina barkeri * substrate regimes * diversity * co-expression * ecological strategies Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 3.420, year: 2016

  12. Co-expression of the C-terminal domain of Yersinia enterocolitica ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 40; Issue 1. Co-expression of the C-terminal domain of Yersinia enterocolitica invasin enhances the efficacy of classical swine-fever-vectored vaccine based on human adenovirus. Helin Li Pengbo Ning Zhi Lin Wulong Liang Kai Kang Lei He Yanming Zhang. Articles Volume ...

  13. Differentiating clinical care from disease prevention: a prerequisite for practicing quaternary prevention

    Directory of Open Access Journals (Sweden)

    Charles Dalcanale Tesser

    Full Text Available Abstract: This article contends that the distinction between clinical care (illness and prevention of future disease is essential to the practice of quaternary prevention. The authors argue that the ongoing entanglement of clinical care and prevention transforms healthy into "sick" people through changes in disease classification criteria and/or cut-off points for defining high-risk states. This diverts health care resources away from those in need of care and increases the risk of iatrogenic harm in healthy people. The distinction in focus is based on: (a management of uncertainty (more flexible when caring for ill persons; (b guarantee of benefit (required only in prevention; (c harm tolerance (nil or minimal in prevention. This implies attitudinal differences in the decision-making process: greater skepticism, scientism and resistance towards preventive action. These should be based on high-quality scientific evidence of end-outcomes that displays a net positive harm/benefit ratio.

  14. Population differentiation of the Chagas disease vector Triatoma maculata (Erichson, 1848) from Colombia and Venezuela.

    Science.gov (United States)

    Monsalve, Yoman; Panzera, Francisco; Herrera, Leidi; Triana-Chávez, Omar; Gómez-Palacio, Andrés

    2016-06-01

    The emerging vector of Chagas disease, Triatoma maculata (Hemiptera, Reduviidae), is one of the most widely distributed Triatoma species in northern South America. Despite its increasing relevance as a vector, no consistent picture of the magnitude of genetic and phenetic diversity has yet been developed. Here, several populations of T. maculata from eleven Colombia and Venezuela localities were analyzed based on the morphometry of wings and the mitochondrial NADH dehydrogenase subunit 4 (ND4) gene sequences. Our results showed clear morphometric and genetic differences among Colombian and Venezuelan populations, indicating high intraspecific diversity. Inter-population divergence is suggested related to East Cordillera in Colombia. Analyses of other populations from Colombia, Venezuela, and Brazil from distinct eco-geographic regions are still needed to understand its systematics and phylogeography as well as its actual role as a vector of Chagas disease. © 2016 The Society for Vector Ecology.

  15. Detection of interferon alpha protein reveals differential levels and cellular sources in disease.

    Science.gov (United States)

    Rodero, Mathieu P; Decalf, Jérémie; Bondet, Vincent; Hunt, David; Rice, Gillian I; Werneke, Scott; McGlasson, Sarah L; Alyanakian, Marie-Alexandra; Bader-Meunier, Brigitte; Barnerias, Christine; Bellon, Nathalia; Belot, Alexandre; Bodemer, Christine; Briggs, Tracy A; Desguerre, Isabelle; Frémond, Marie-Louise; Hully, Marie; van den Maagdenberg, Arn M J M; Melki, Isabelle; Meyts, Isabelle; Musset, Lucile; Pelzer, Nadine; Quartier, Pierre; Terwindt, Gisela M; Wardlaw, Joanna; Wiseman, Stewart; Rieux-Laucat, Frédéric; Rose, Yoann; Neven, Bénédicte; Hertel, Christina; Hayday, Adrian; Albert, Matthew L; Rozenberg, Flore; Crow, Yanick J; Duffy, Darragh

    2017-05-01

    Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation. © 2017 Rodero et al.

  16. Differential Diagnoses of Overgrowth Syndromes: The Most Important Clinical and Radiological Disease Manifestations

    International Nuclear Information System (INIS)

    Lacerda, L.S.; Alves, U.D.; Zanier, J.F.C.; Machado, D.C.; Camilo, G.B.; Machado, D.C.; Camilo, G.B.; Lopes, A.J.

    2014-01-01

    Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Some of these syndromes may be associated with dysfunction in the receptor tyrosine kinase (RTK)/PI3K/AKT pathway, which results in an increased expression of the insulin receptor. In the current review, four overgrowth syndromes were characterized (Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Made lung’s disease, and neurofibromatosis type I) and illustrated using cases from our institution. Because these syndromes have overlapping clinical manifestations and have no established genetic tests for their diagnosis, radiological methods are important contributors to the diagnosis of many of these syndromes. The correlation of genetic discoveries and molecular pathways that may contribute to the phenotypic expression is also of interest, as this may lead to potential therapeutic interventions

  17. gamAID: Greedy CP tensor decomposition for supervised EHR-based disease trajectory differentiation.

    Science.gov (United States)

    Henderson, Jette; Ho, Joyce; Ghosh, Joydeep

    2017-07-01

    We propose gamAID, an exploratory, supervised nonnegative tensor factorization method that iteratively extracts phenotypes from tensors constructed from medical count data. Using data from diabetic patients who later on get diagnosed with chronic kidney disorder (CKD) as well as diabetic patients who do not receive a CKD diagnosis, we demonstrate the potential of gamAID to discover phenotypes that characterize patients who are at risk for developing a disease.

  18. The clinical differentiation of fronto-temporal dementia from psychiatric disease

    OpenAIRE

    Panegyres, Peter K; Graves, Angela; Frencham, Kate AR

    2007-01-01

    Objective Frontal and/or temporal lobar atrophy (F/TA) is sometimes detected on neuroimaging in patients with psychiatric disease. This observation leads to difficulty in distinguishing whether patients have fronto-temporal dementia (FTD) or psychiatric illness. This paper sets out to develop clinical profiles that might be useful at first presentation to distinguish these two populations. Methods 29 patients were selected from a database of 250 current patients attending young onset dementia...

  19. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    Directory of Open Access Journals (Sweden)

    Scanlon SA

    2011-12-01

    Full Text Available Samantha A Scanlon1, Joseph A Murray1,21Department of Internal Medicine, 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Celiac disease (CD is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions.Keywords: immune-mediated enteropathy, gliadin, gluten, epidemiology, CD diagnosis, therapy

  20. Logistic discriminant parametric mapping: a novel method for the pixel-based differential diagnosis of Parkinson's disease

    International Nuclear Information System (INIS)

    Acton, P.D.; Mozley, P.D.; Kung, H.F.; Pennsylvania Univ., Philadelphia, PA

    1999-01-01

    Positron emission tomography (PET) and single-photon emission tomography (SPET) imaging of the dopaminergic system is a powerful tool for distinguishing groups of patients with neurodegenerative disorders, such as Parkinson's disease (PD). However, the differential diagnosis of individual subjects presenting early in the progress of the disease is much more difficult, particularly using region-of-interest analysis where small localized differences between subjects are diluted. In this paper we present a novel pixel-based technique using logistic discriminant analysis to distinguish between a group of PD patients and age-matched healthy controls. Simulated images of an anthropomorphic head phantom were used to test the sensitivity of the technique to striatal lesions of known size. The methodology was applied to real clinical SPET images of binding of technetium-99m labelled TRODAT-1 to dopamine transporters in PD patients (n=42) and age-matched controls (n=23). The discriminant model was trained on a subset (n=17) of patients for whom the diagnosis was unequivocal. Logistic discriminant parametric maps were obtained for all subjects, showing the probability distribution of pixels classified as being consistent with PD. The probability maps were corrected for correlated multiple comparisons assuming an isotropic Gaussian point spread function. Simulated lesion sizes measured by logistic discriminant parametric mapping (LDPM) gave strong correlations with the known data (r 2 =0.985, P<0.001). LDPM correctly classified all PD patients (sensitivity 100%) and only misclassified one control (specificity 95%). All patients who had equivocal clinical symptoms associated with early onset PD (n=4) were correctly assigned to the patient group. Statistical parametric mapping (SPM) had a sensitivity of only 24% on the same patient group. LDPM is a powerful pixel-based tool for the differential diagnosis of patients with PD and healthy controls. The diagnosis of disease even

  1. Comparison of co-expression measures: mutual information, correlation, and model based indices.

    Science.gov (United States)

    Song, Lin; Langfelder, Peter; Horvath, Steve

    2012-12-09

    Co-expression measures are often used to define networks among genes. Mutual information (MI) is often used as a generalized correlation measure. It is not clear how much MI adds beyond standard (robust) correlation measures or regression model based association measures. Further, it is important to assess what transformations of these and other co-expression measures lead to biologically meaningful modules (clusters of genes). We provide a comprehensive comparison between mutual information and several correlation measures in 8 empirical data sets and in simulations. We also study different approaches for transforming an adjacency matrix, e.g. using the topological overlap measure. Overall, we confirm close relationships between MI and correlation in all data sets which reflects the fact that most gene pairs satisfy linear or monotonic relationships. We discuss rare situations when the two measures disagree. We also compare correlation and MI based approaches when it comes to defining co-expression network modules. We show that a robust measure of correlation (the biweight midcorrelation transformed via the topological overlap transformation) leads to modules that are superior to MI based modules and maximal information coefficient (MIC) based modules in terms of gene ontology enrichment. We present a function that relates correlation to mutual information which can be used to approximate the mutual information from the corresponding correlation coefficient. We propose the use of polynomial or spline regression models as an alternative to MI for capturing non-linear relationships between quantitative variables. The biweight midcorrelation outperforms MI in terms of elucidating gene pairwise relationships. Coupled with the topological overlap matrix transformation, it often leads to more significantly enriched co-expression modules. Spline and polynomial networks form attractive alternatives to MI in case of non-linear relationships. Our results indicate that MI

  2. Evaluation of gene association methods for coexpression network construction and biological knowledge discovery.

    Directory of Open Access Journals (Sweden)

    Sapna Kumari

    Full Text Available BACKGROUND: Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. METHODS AND RESULTS: In this study, we compared eight gene association methods - Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson - and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. CONCLUSIONS: We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

  3. Apraxia for differentiating Alzheimer’s disease from subcortical vascular dementia and mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ozkan S

    2013-07-01

    Full Text Available Serhat Ozkan,1 Demet Ozbabalik Adapinar,1 Nese Tuncer Elmaci,2 Didem Arslantas31Department of Neurology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey; 2Department of Neurology, Marmara University Medical Faculty, Istanbul, Turkey; 3Department of Public Health, Eskisehir Osmangazi University Medical Faculty, Eskisehir, TurkeyAbstract: Although ideomotor limb apraxia is considered to be a typical sign of cortical pathologies such as Alzheimer’s disease (AD, it has been also reported in subcortical neurodegenerative diseases and vascular lesions. We aimed to investigate the difference between AD, subcortical vascular dementia (SVaD and mild cognitive impairment (MCI patients by means of ideomotor limb apraxia frequency and severity. Ninety-six AD, 72 SVaD, and 84 MCI patients were assessed with the mini-mental status examination (MMSE, clinical dementia rating (CDR and the apraxia screening test of TULIA (AST. Apraxia was significantly more frequent in the AD patients (32.3% than in both of the SVaD (16.7% and MCI (4.8% patients. The frequency of apraxia was also significantly higher in SVaD patients than in MCI patients. AD patients had significantly lower apraxia scores than both SVaD and MCI patients. In addition, a significant difference was found between SVaD and MCI patients in terms of apraxia scores. These results suggest that the widespread belief of the association between apraxia and cortical dementias is not exactly correct. The significant difference between both of the dementia groups and the MCI patients suggests that the absence of apraxia can be an indicator for MCI diagnosis.Keywords: apraxia, Alzheimer’s disease, subcortical vascular dementia, mild cognitive impairment

  4. Differential disease resistance response in the barley necrotic mutant nec1

    Directory of Open Access Journals (Sweden)

    Kunga Laura

    2011-04-01

    Full Text Available Abstract Background Although ion fluxes are considered to be an integral part of signal transduction during responses to pathogens, only a few ion channels are known to participate in the plant response to infection. CNGC4 is a disease resistance-related cyclic nucleotide-gated ion channel. Arabidopsis thaliana CNGC4 mutants hlm1 and dnd2 display an impaired hypersensitive response (HR, retarded growth, a constitutively active salicylic acid (SA-mediated pathogenesis-related response and elevated resistance against bacterial pathogens. Barley CNGC4 shares 67% aa identity with AtCNGC4. The barley mutant nec1 comprising of a frame-shift mutation of CNGC4 displays a necrotic phenotype and constitutively over-expresses PR-1, yet it is not known what effect the nec1 mutation has on barley resistance against different types of pathogens. Results nec1 mutant accumulated high amount of SA and hydrogen peroxide compared to parental cv. Parkland. Experiments investigating nec1 disease resistance demonstrated positive effect of nec1 mutation on non-host resistance against Pseudomonas syringae pv. tomato (Pst at high inoculum density, whereas at normal Pst inoculum concentration nec1 resistance did not differ from wt. In contrast to augmented P. syringae resistance, penetration resistance against biotrophic fungus Blumeria graminis f. sp. hordei (Bgh, the causal agent of powdery mildew, was not altered in nec1. The nec1 mutant significantly over-expressed race non-specific Bgh resistance-related genes BI-1 and MLO. Induction of BI-1 and MLO suggested putative involvement of nec1 in race non-specific Bgh resistance, therefore the effect of nec1on mlo-5-mediated Bgh resistance was assessed. The nec1/mlo-5 double mutant was as resistant to Bgh as Nec1/mlo-5 plants, suggesting that nec1 did not impair mlo-5 race non-specific Bgh resistance. Conclusions Together, the results suggest that nec1 mutation alters activation of systemic acquired resistance

  5. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease

    DEFF Research Database (Denmark)

    Cloos, Paul A C; Christensen, Jesper; Agger, Karl

    2008-01-01

    The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone...... demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases......, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer....

  6. A Differentiated Approach to the Prescription of Antihistamines in Allergic Diseases in Childhood

    Directory of Open Access Journals (Sweden)

    O.Ye. Abaturov

    2016-08-01

    Full Text Available The comparative analysis of current data on pharmacodynamics, pharmacokinetics, clinical efficacy and side effects of the first generation drug antihistamine demetinden and the third-generation levocetirizinum is presented. Levocetirizinum shows the highest selectivity to H1-receptor having anta­gonist properties does not penetrate the central nervous system and has no sedative effects. The drug has anti-inflammatory effects due to suppression of release of inflammation mediators and cellular response. Levocetirizinum has favorable pharmacokinetics and half-life, no drug interactions. The clinical stu­dies demonstrated its high efficiency in ruducing the symptoms of allergic diseases.

  7. Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome.

    Science.gov (United States)

    Clotman, Frédéric; Libbrecht, Louis; Killingsworth, Murray C; Loo, Christine C K; Roskams, Tania; Lemaigre, Frédéric P

    2008-03-01

    Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome. Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy. The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers. Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.

  8. LABORATORY BIOMARKERS TO FACILITATE DIFFERENTIAL DIAGNOSIS BETWEEN MEASLES AND KAWASAKI DISEASE IN A PEDIATRIC EMERGENCY ROOM: A RETROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Danilo Buonsenso

    2018-05-01

    Full Text Available This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD at first evaluation in a emergency room. We found similar clinical features as duration of fever and number of KD criteria (p >0.5 but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001. LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

  9. Differential Diagnosis of Parkinson Disease, Essential Tremor, and Enhanced Physiological Tremor with the Tremor Analysis of EMG

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2017-01-01

    Full Text Available We investigate the differential diagnostic value of tremor analysis of EMG on Parkinson’s disease (PD, essential tremor (ET, and enhanced physiological tremor (EPT. Clinical data from 25 patients with PD, 20 patients with ET, and 20 patients with EPT were collected. The tremor frequency and muscle contraction pattern of the resting, posture, and 500 g and 1000 g overload were recorded. The frequency of PD tremor was 4–6 Hz, and the frequency of ET was also in this range; the frequency of EPT is 6–12 hz having some overlap with PD. The muscle contraction patterns of the ET and EPT group were mainly synchronous contraction, and the muscle contraction mode of the PD group was mainly alternating contraction. Having tremor latency from rest to postural position and having changes in tremor amplitude after mental concentration in PD might distinguish ET. Tremor analysis of EMG was able to distinguish PD from ET and EPT by varying the tremor frequency and muscle contraction pattern. It can also differentiate between PD and ET by the latency and concentration effect and ET and EPT by weight load effect.

  10. Multiparametric computer-aided differential diagnosis of Alzheimer's disease and frontotemporal dementia using structural and advanced MRI

    International Nuclear Information System (INIS)

    Bron, Esther E.; Klein, Stefan; Smits, Marion; Steketee, Rebecca M.E.; Meijboom, Rozanna; Papma, Janne M.; Swieten, John C. van; Groot, Marius de; Niessen, Wiro J.

    2017-01-01

    To investigate the added diagnostic value of arterial spin labelling (ASL) and diffusion tensor imaging (DTI) to structural MRI for computer-aided classification of Alzheimer's disease (AD), frontotemporal dementia (FTD), and controls. This retrospective study used MRI data from 24 early-onset AD and 33 early-onset FTD patients and 34 controls (CN). Classification was based on voxel-wise feature maps derived from structural MRI, ASL, and DTI. Support vector machines (SVMs) were trained to classify AD versus CN (AD-CN), FTD-CN, AD-FTD, and AD-FTD-CN (multi-class). Classification performance was assessed by the area under the receiver-operating-characteristic curve (AUC) and accuracy. Using SVM significance maps, we analysed contributions of brain regions. Combining ASL and DTI with structural MRI resulted in higher classification performance for differential diagnosis of AD and FTD (AUC = 84%; p = 0.05) than using structural MRI by itself (AUC = 72%). The performance of ASL and DTI themselves did not improve over structural MRI. The classifications were driven by different brain regions for ASL and DTI than for structural MRI, suggesting complementary information. ASL and DTI are promising additions to structural MRI for classification of early-onset AD, early-onset FTD, and controls, and may improve the computer-aided differential diagnosis on a single-subject level. (orig.)

  11. Waveform analysis of tremor may help to differentiate Parkinson's disease from drug-induced parkinsonism

    International Nuclear Information System (INIS)

    Jang, W; Han, J; Kim, I Y; Park, J; Kim, J-S; Cho, J W; Koh, S-B; Chung, S J; Kim, H-T

    2013-01-01

    In this study, we analyzed the waveform characteristics of resting tremor by accelerometer recordings in patients with drug-induced parkinsonism (DIP) and Parkinson's disease (PD). We prospectively recruited 12 patients with tremulous PD and 12 patients with DIP presenting with resting tremor. Tremor was recorded from the more affected side and was recorded twice for a 60 s period in each patient. Peak frequency, amplitude and all harmonic peaks were obtained, and the asymmetry of the decay of the autocorrelation function, third momentum and time-reversal invariance were also computed using a mathematical algorithm. Among the parameters used in the waveform analysis, the harmonic ratio, time-reversal invariance and asymmetric decay of the autocorrelation function were different between PD and DIP at a statistically significant level (all p < 0.01). The total harmonic peak power and third momentum in the time series were not significantly different. The clinical characteristics of DIP patients may be similar to those of PD patients in some cases, which makes the clinical differentiation between DIP and PD challenging. Our study shows that the identification of parameters reflecting waveform asymmetry might be helpful in differentiating between DIP and PD. (note)

  12. Validation of mobile eye tracking as novel and efficient means for differentiating progressive supranuclear palsy from Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Svenja eMarx

    2012-12-01

    Full Text Available Background: The decreased ability to carry out vertical saccades is a key symptom of Progressive Supranuclear Palsy (PSP. Objective measurement devices can help to reliably detect subtle eye-movement disturbances to improve sensitivity and specificity of the clinical diagnosis. The present study aims at transferring findings from restricted stationary video-oculography to a wearable head-mounted device, which can be readily applied in clinical practice.Methods: We investigated the eye movements in 10 possible or probable PSP patients, 11 Parkinson’s disease (PD patients and 10 age-matched healthy controls (HC using a mobile, gaze-driven video camera setup (EyeSeeCam. Ocular movements were analyzed during a standardized fixation protocol and in an unrestricted real-life scenario while walking along a corridor.Results: The EyeSeeCam detected prominent impairment of both saccade velocity and amplitude in PSP patients, differentiating them from PD and HCs. Differences were particularly evident for saccades in the vertical plane, and stronger for saccades than for other eye movements. Differences were more pronounced during the standardized protocol than in the real-life scenario. Conclusions: Combined analysis of saccade velocity and saccade amplitude during the fixation protocol with the EyeSeeCam provides a simple, rapid (< 20s and reliable tool to differentiate clinically established PSP patients from PD and HCs. As such, our findings prepare the ground for using wearable eye-tracking in patients with uncertain diagnoses.

  13. Multiparametric computer-aided differential diagnosis of Alzheimer's disease and frontotemporal dementia using structural and advanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Bron, Esther E.; Klein, Stefan [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Smits, Marion; Steketee, Rebecca M.E.; Meijboom, Rozanna [Erasmus MC, Department of Radiology and Nuclear Medicine, Rotterdam (Netherlands); Papma, Janne M.; Swieten, John C. van [Erasmus MC, Department of Neurology, Rotterdam (Netherlands); Groot, Marius de [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Erasmus MC, Department of Epidemiology, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology and Nuclear Medicine, Office Na2502, P.O. Box 2040, Rotterdam (Netherlands); Delft University of Technology, Imaging Physics, Applied Sciences, Delft (Netherlands)

    2017-08-15

    To investigate the added diagnostic value of arterial spin labelling (ASL) and diffusion tensor imaging (DTI) to structural MRI for computer-aided classification of Alzheimer's disease (AD), frontotemporal dementia (FTD), and controls. This retrospective study used MRI data from 24 early-onset AD and 33 early-onset FTD patients and 34 controls (CN). Classification was based on voxel-wise feature maps derived from structural MRI, ASL, and DTI. Support vector machines (SVMs) were trained to classify AD versus CN (AD-CN), FTD-CN, AD-FTD, and AD-FTD-CN (multi-class). Classification performance was assessed by the area under the receiver-operating-characteristic curve (AUC) and accuracy. Using SVM significance maps, we analysed contributions of brain regions. Combining ASL and DTI with structural MRI resulted in higher classification performance for differential diagnosis of AD and FTD (AUC = 84%; p = 0.05) than using structural MRI by itself (AUC = 72%). The performance of ASL and DTI themselves did not improve over structural MRI. The classifications were driven by different brain regions for ASL and DTI than for structural MRI, suggesting complementary information. ASL and DTI are promising additions to structural MRI for classification of early-onset AD, early-onset FTD, and controls, and may improve the computer-aided differential diagnosis on a single-subject level. (orig.)

  14. Diagnostic accuracy of the clinical and CT findings for differentiating Kikuchi's disease and tuberculous lymphadenitis presenting with cervical lymphadenopathy.

    Science.gov (United States)

    Baek, Hye Jin; Lee, Jeong Hyun; Lim, Hyun Kyung; Lee, Ha Young; Baek, Jung Hwan

    2014-11-01

    To determine the optimal clinical and CT findings for differentiating Kikuchi's disease (KD) and tuberculous lymphadenitis (TB) in patients presenting with cervical lymphadenopathy. From 2006 to 2010, 87 consecutive patients who were finally diagnosed with KD or TB were enrolled. Two radiologists performed independent analysis of contrast-enhanced neck CT images with regard to the involvement pattern, nodal or perinodal changes, and evidence of the previous infection. Significant clinical and CT findings of KD were determined by statistical analyses. Of the 87 patients, 27 (31%) were classified as having KD and 60 (69%) as having TB. Statistically significant findings of KD patients were younger age, presence of fever, involvement of ≥5 nodal levels or the bilateral neck, no or minimal nodal necrosis, marked perinodal infiltration, and no evidence of upper lung lesion or mediastinal lymphadenopathy. The presence of four or more statistically significant clinical and CT findings of KD had the largest area under the receiver-operating characteristic curve (A z = 0.861; 95% confidence intervals 0.801, 0.909), with a sensitivity of 89% and specificity of 83%. CT can be a helpful tool for differentiating KD from TB, especially when it is combined with the clinical findings.

  15. Differential patterns of implicit emotional processing in Alzheimer's disease and healthy aging.

    Science.gov (United States)

    García-Rodríguez, Beatriz; Fusari, Anna; Rodríguez, Beatriz; Hernández, José Martín Zurdo; Ellgring, Heiner

    2009-01-01

    Implicit memory for emotional facial expressions (EFEs) was investigated in young adults, healthy old adults, and mild Alzheimer's disease (AD) patients. Implicit memory is revealed by the effect of experience on performance by studying previously encoded versus novel stimuli, a phenomenon referred to as perceptual priming. The aim was to assess the changes in the patterns of priming as a function of aging and dementia. Participants identified EFEs taken from the Facial Action Coding System and the stimuli used represented the emotions of happiness, sadness, surprise, fear, anger, and disgust. In the study phase, participants rated the pleasantness of 36 faces using a Likert-type scale. Subsequently, the response to the 36 previously studied and 36 novel EFEs was tested when they were randomly presented in a cued naming task. The results showed that implicit memory for EFEs is preserved in AD and aging, and no specific age-related effects on implicit memory for EFEs were observed. However, different priming patterns were evident in AD patients that may reflect pathological brain damage and the effect of stimulus complexity. These findings provide evidence of how progressive neuropathological changes in the temporal and frontal areas may affect emotional processing in more advanced stages of the disease.

  16. Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data

    International Nuclear Information System (INIS)

    Szigeti, Krisztián; Szabó, Tibor; Korom, Csaba; Czibak, Ilona; Horváth, Ildikó; Veres, Dániel S.; Gyöngyi, Zoltán; Karlinger, Kinga; Bergmann, Ralf; Pócsik, Márta; Budán, Ferenc; Máthé, Domokos

    2016-01-01

    Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann–Whitney post hoc (MWph) tests were used. Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas. The online version of this article (doi:10.1186/s12880-016-0118-z) contains supplementary material, which is available to authorized users

  17. Planning and task management in Parkinson's disease: differential emphasis in dual-task performance.

    Science.gov (United States)

    Bialystok, Ellen; Craik, Fergus I M; Stefurak, Taresa

    2008-03-01

    Seventeen patients diagnosed with Parkinson's disease completed a complex computer-based task that involved planning and management while also performing an attention-demanding secondary task. The tasks were performed concurrently, but it was necessary to switch from one to the other. Performance was compared to a group of healthy age-matched control participants and a group of young participants. Parkinson's patients performed better than the age-matched controls on almost all measures and as well as the young controls in many cases. However, the Parkinson's patients achieved this by paying relatively less attention to the secondary task and focusing attention more on the primary task. Thus, Parkinson's patients can apparently improve their performance on some aspects of a multidimensional task by simplifying task demands. This benefit may occur as a consequence of their inflexible exaggerated attention to some aspects of a complex task to the relative neglect of other aspects.

  18. Differential Effects of Tango Versus Dance for PD in Parkinson Disease

    Science.gov (United States)

    McNeely, Marie E.; Mai, Marina M.; Duncan, Ryan P.; Earhart, Gammon M.

    2015-01-01

    Over half of the general population does not achieve recommended daily levels of physical activity, and activity levels in people with Parkinson disease (PD) are lower than in healthy older adults. Dance can serve as an adjunct to traditional treatments to improve gait, balance, and quality of life in people with PD. This study directly compares a tango dance intervention and a dance intervention based on the Dance for PD model, which integrates multiple dance styles. Eleven people with PD participated in a community-based mixed styles dance intervention called Dance for Parkinson’s (D4PD). Participants in the D4PD group were matched to participants in an ongoing community-based exercise study who participated in tango dance. The groups received 12 weeks of intervention, attending 1-h group classes twice a week. Participants were evaluated off anti-PD medication before and after intervention. Measures of balance, repeated sit-to-stand performance and endurance (mini-balance evaluation systems test, four square step test, five times sit to stand, 6-min walk time) improved from pre to post similarly in both groups. Motor sign severity (movement disorders society unified Parkinson disease rating scale motor subsection) and functional mobility (timed up and go) improved in the tango group and worsened in the D4PD group. Gait velocity was not affected by either intervention. Direct comparisons of different interventions are ­critical for developing optimal exercise interventions designed to specifically target motor impairments in PD. Tango dance interventions may preferentially improve mobility and motor signs in people with PD, compared to D4PD. PMID:26733865

  19. Differential pharmacological effects on brain reactivity and plasticity in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Anna-Katharine eBrem

    2013-10-01

    Full Text Available Acetylcholinesterase inhibitors (AChEI are the most commonly prescribed monotherapeutic medications for Alzheimer’s disease (AD. However, their underlying neurophysiological effects remain largely unknown.We investigated the effects of monotherapy (AChEI and combination therapy (AChEI and memantine on brain reactivity and plasticity. Patients treated with monotherapy (AChEI (N=7 were compared to patients receiving combination therapy (COM (N=9 and a group of age-matched, healthy controls (HC (N=13. Cortical reactivity and plasticity of the motor cortex (MC were examined using transcranial magnetic stimulation (TMS. Cognitive functions were assessed with the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog, activities of daily living with the ADCS-ADL. In addition we assessed the degree of brain atrophy by measuring brain-scalp distances in seven different brain areas.Patient groups differed in resting motor threshold and brain atrophy, with COM showing a lower motor threshold but less atrophy than AChEI. COM showed similar plasticity effects as the HC group, while plasticity was reduced in AChEI. Long-interval intracortical inhibition (LICI was impaired in both patient groups when compared to HC. ADAS-Cog scores were positively correlated with LICI measures and with brain atrophy, specifically in the left IPL.AD patients treated with mono- or combination therapy show distinct neurophysiological patterns. Further studies should investigate whether these measures might serve as biomarkers of treatment response and whether they could guide other therapeutic interventions.

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

    Science.gov (United States)

    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.

  1. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  2. New and Improved T-wave Morphology Parameters to Differentiate Healthy Individuals from those with Cardiomyopathy and Coronary Artery Disease

    Science.gov (United States)

    Greco, E. C.; Schlegel, T. T.; Arenare, B.; DePalma, J. L.; Starc, V.; Rahman, M. A.; Delgado, R.

    2007-01-01

    We investigated the ability of several known as well as new ECG repolarization parameters to differentiate healthy individuals from patients with obstructive coronary artery disease (CAD) and cardiomyopathy (CM). Advanced high-fidelity 12-lead ECG tests (approx. 5-min supine) were first performed on a "training set" of 99 individuals: 33 with ischemic or dilated CM and low ejection fraction (EF less than 40%); 33 with catheterization-proven obstructive CAD but normal EF; and 33 age-/gender-matched healthy controls. The following multiple parameters of T-wave morphology (TWM) were derived via signal averaging and singular value decomposition (SVD, which yields 8 eigenvalues, rho(sub 1) greater than rho(sub 2)...greater than rho(sub 8) and studied for their retrospective accuracy in detecting underlying disease: 1) Principal component analysis ratio of the T wave (T-PCA) = 100*rho(sub 2)/rho(sub 1); 2) Relative T-wave residuum (rTWR) = 100* SIGMA (rho(sub 4)(sup 2) +...+ rho(sub 8)(sup 2)); 3) Modified complexity ratio of the T wave (T-mCR) = 100*SIGMA(rho(sub 3)(sup 2) +...+rho(sb 8) (sup 2)); and 4) Normalized 3-dimensional volume of the T wave (nTV) = 100*(rho(sub 2)*rho(sub 3)/rho(sub 1)(sup 2). All TWM parameters significantly differentiated CAD from controls (p less than 0.0001), and also CM from controls (p less than 0.0001). Retrospective areas under the ROC curve were 0.77, 0.81, 0.82, and 0.83 (CAD vs. controls) and 0.93, 0.89, 0.95 and 0.96 (CM vs. controls) for T-PCA, rTWR, T-mCR and nTV respectively. The newer TWM parameters (T-mCR and nTV) thus outperformed the more established parameters (T-PCA and rTWR), presumably by putting a greater emphasis on the third T-wave eigenvalue, which in most healthy subjects has little energy compared to the first two eigenvalues. Subsequent prospective analyses have also yielded similar results, such that we conclude that diagnostic differentiation of pathology from non-pathology may be especially aided by detecting

  3. Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Tanaka R

    2018-04-01

    Full Text Available Rie Tanaka,1 Hisatoshi Sugiura,1 Mitsuhiro Yamada,1 Tomohiro Ichikawa,1 Akira Koarai,1 Naoya Fujino,1 Satoru Yanagisawa,1 Katsuhiro Onodera,1 Tadahisa Numakura,1 Kei Sato,1 Yorihiko Kyogoku,1 Hirohito Sano,1 Shun Yamanaka,1 Tatsuma Okazaki,1 Tsutomu Tamada,1 Motohiko Miura,2 Tsuneyuki Takahashi,3 Masakazu Ichinose1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan; 2Department of Respiratory Medicine, Tohoku Rosai Hospital, Aoba-ku, Sendai, Japan; 3Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Wakabayashi-ku, Sendai, Japan Background: Growth differentiation factor 11 (GDF11 is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. Patients and methods: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. Results: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were

  4. VTCdb: a gene co-expression database for the crop species Vitis vinifera (grapevine).

    Science.gov (United States)

    Wong, Darren C J; Sweetman, Crystal; Drew, Damian P; Ford, Christopher M

    2013-12-16

    Gene expression datasets in model plants such as Arabidopsis have contributed to our understanding of gene function and how a single underlying biological process can be governed by a diverse network of genes. The accumulation of publicly available microarray data encompassing a wide range of biological and environmental conditions has enabled the development of additional capabilities including gene co-expression analysis (GCA). GCA is based on the understanding that genes encoding proteins involved in similar and/or related biological processes may exhibit comparable expression patterns over a range of experimental conditions, developmental stages and tissues. We present an open access database for the investigation of gene co-expression networks within the cultivated grapevine, Vitis vinifera. The new gene co-expression database, VTCdb (http://vtcdb.adelaide.edu.au/Home.aspx), offers an online platform for transcriptional regulatory inference in the cultivated grapevine. Using condition-independent and condition-dependent approaches, grapevine co-expression networks were constructed using the latest publicly available microarray datasets from diverse experimental series, utilising the Affymetrix Vitis vinifera GeneChip (16 K) and the NimbleGen Grape Whole-genome microarray chip (29 K), thus making it possible to profile approximately 29,000 genes (95% of the predicted grapevine transcriptome). Applications available with the online platform include the use of gene names, probesets, modules or biological processes to query the co-expression networks, with the option to choose between Affymetrix or Nimblegen datasets and between multiple co-expression measures. Alternatively, the user can browse existing network modules using interactive network visualisation and analysis via CytoscapeWeb. To demonstrate the utility of the database, we present examples from three fundamental biological processes (berry development, photosynthesis and flavonoid biosynthesis

  5. Hand osteoarthritis: Differential diagnosis with inflammatory joint diseases and treatment policy

    Directory of Open Access Journals (Sweden)

    Yu. A. Olyunin

    2015-01-01

    Full Text Available Osteoarthritis (OA usually affects certain joint groups selectively and the hand joints (HJ are one of its classical locations. Hand OA is widespread in the population. In their practice rheumatologists encounter HJ injury in OA in 38% of cases. It is conventional to identify three main types of hand OA. These are 1 interphalangeal OA that may or may not be accompanied by nodulation; 2 first carpometacarpal OA; and 3 erosive OA. At the same time, the rate of clinical forms ranges from 2.0 to 6.2%; it is 4.7 to 20.4% in the elderly. Nonsteroidal antiinflammatory drugs (NSAIDs are most commonly used to relieve pain that is the main manifestation of the disease. The risk for NSAID-related adverse gastrointestinal (GI events is substantially reduced by the drugs that exert their effects mainly on cyclooxygenase 2. These include nimesulide in particular. Undesirable GI effects may be also considerably minimized by using NSAIDs that have both their gastroprotective and antiinflammatory activities. By suppressing pain and inflammatory changes, the recently designed NSAID amtolmetin guacil simultaneously exerts a protective effect on the GI mucosa, by elevating its nitric oxide levels.

  6. Insulin is Differentially Related to Cognitive Decline and Atrophy in Alzheimer’s Disease and Aging

    Science.gov (United States)

    Burns, Jeffrey M.; Honea, Robyn A.; Vidoni, Eric D.; Hutfles, Lewis; Brooks, William M.; Swerdlow, Russell H.

    2012-01-01

    We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer’s disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=−0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. PMID:21745566

  7. Galactographic differentiation between malignant and benign disease in patients with pathologic nipple discharge

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya; Cho, Hyun Yee [Gil Medical Center, Incheon (Korea, Republic of); Oh, Ki Keun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2003-06-01

    To compare the galactographic findings of malignant and benign disease in patients with pathologic nipple discharge and to analyze the features suggesting malignancy. In 24 patients in whom pathologic nipple discharge had occurred, the findings of preoperative galactography were correlated with those of pathology. Nine of the 24 cases were malignant and the other 15 were benign. Intraductal calcification occurred in five malignant cases (56%) and two (13%) which were benign. Seven malignant cases (78%) involved the segmental ducts, and in eight (89%), the peripheral ducts below the subsegmental duct were involved. Five benign cases (33%) involved the lactiferous sinus, seven (47%) the segmental duct, and two (13%) the subsegmental duct. Distal duct dilatation occurred in four benign cases (27%), while ductal stenosis was noted in six cases (67%) and ductal distortion in seven (78%). A malignant tumor appeared as a multiple (n=5, 56%) or irregular (n=5, 56%) filling defect, and a benign tumor as a single (n=12, 80%), oval (n=6, 40%) or lobular (n=4, 27%) filling defect. At galactography, a malignant tumor frequently appeared as an irregular multiple intraductal filling defect in a peripheral duct. A benign tumor, on the other hand, appeared as an oval or lobular single lesion. The presence of ductal stenosis, distortion and intraductal microcalcifications not opacified by contrast material suggest possible malignancy.

  8. Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

    Science.gov (United States)

    Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Talcott, Stephen T.; Ono, Kenjiro; Teplow, David; Humala, Nelson; Cheng, Alice; Percival, Susan S.; Ferruzzi, Mario; Janle, Elsa; Dickstein, Dara L.; Pasinetti, Giulio Maria

    2009-01-01

    We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms. PMID:19158422

  9. Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease.

    Science.gov (United States)

    Scorza, Breanna M; Wacker, Mark A; Messingham, Kelly; Kim, Peter; Klingelhutz, Aloysius; Fairley, Janet; Wilson, Mary E

    2017-10-01

    All Leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. Incubation of primary or immortalized human keratinocytes with Leishmania infantum or Leishmania major, which cause visceral or cutaneous leishmaniasis, respectively, elicited dramatically different responses. Keratinocytes incubated with L. infantum significantly increased expression of proinflammatory genes for IL-6, IL-8, tumor necrosis factor, and IL-1B, whereas keratinocytes exposed to several L. major isolates did not. Furthermore, keratinocyte-monocyte co-incubation studies across a 4 µM semipermeable membrane suggested that L. infantum-exposed keratinocytes release soluble factors that enhance monocyte control of intracellular L. infantum replication (P Leishmania species that may affect the course of disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer’s Disease Individuals

    Directory of Open Access Journals (Sweden)

    Darine Villela

    2016-01-01

    Full Text Available This study investigated for the first time the genomewide DNA methylation changes of noncoding RNA genes in the temporal cortex samples from individuals with Alzheimer’s disease (AD. The methylome of 10 AD individuals and 10 age-matched controls were obtained using Illumina 450 K methylation array. A total of 2,095 among the 15,258 interrogated noncoding RNA CpG sites presented differential methylation, 161 of which were associated with miRNA genes. In particular, 10 miRNA CpG sites that were found to be hypermethylated in AD compared to control brains represent transcripts that have been previously associated with the disease. This miRNA set is predicted to target 33 coding genes from the neuregulin receptor complex (ErbB signaling pathway, which is required for the neurons myelination process. For 6 of these miRNA genes (MIR9-1, MIR9-3, MIR181C, MIR124-1, MIR146B, and MIR451, the hypermethylation pattern is in agreement with previous results from literature that shows downregulation of miR-9, miR-181c, miR-124, miR-146b, and miR-451 in the AD brain. Our data implicate dysregulation of miRNA methylation as contributor to the pathogenesis of AD.

  11. Evaluation of using 99Tcm-MDP SPECT/CT for differentiating malignancy from benignancy in femoral diseases

    International Nuclear Information System (INIS)

    Ou Xiaohong; Huang Rui; Su Minggang; Zhou Li'na; Fan Qiuping

    2010-01-01

    Objective: To evaluate the value of SPECT/CT in assessment of femoral foci of abnormal bone metabolism classified as intermediated on bone scanning using 99Tcm-methylene diphosphonate (MDP). Methods: There were 94 patients with solitary femoral abnormal uptake in bone scanning included. SPECT was accompanied by inline CT over the femoral region. All of the images were blindly interpreted independently by two experienced board-certified radiologists. The reference standard was follow-up over half a year of MRI, CT, SPECT, or pathology. Diagnosis which consist with reference were counted as accurate. Diagnosis which either not consist with reference or undetermined were counted as false. Results: Of the 94 patients, 78 patients (male 42 , female 36, mean age 62 yrs) have the definite diagnosis of their femoral foci. 19 were proved to be metastasis and the other 59 were benign diseases. The diagnostic accuracy by bone SPECT, bone CT and fusion imaging were 58.9%, 87.2%, 96.2% respectively. Conclusions: Most of the solitary femoral foci caused by benign diseases. SPECT/CT using 99 Tc m -MDP has additional valuable in differentiating malignancy from benignancy in femoral foci . (authors)

  12. Differential expression of genes encoding anti-oxidant enzymes in Sydney rock oysters, Saccostrea glomerata (Gould) selected for disease resistance.

    Science.gov (United States)

    Green, Timothy J; Dixon, Tom J; Devic, Emilie; Adlard, Robert D; Barnes, Andrew C

    2009-05-01

    Sydney rock oysters (Saccostrea glomerata) selectively bred for disease resistance (R) and wild-caught control oysters (W) were exposed to a field infection of disseminating neoplasia. Cumulative mortality of W oysters (31.7%) was significantly greater than R oysters (0.0%) over the 118 days of the experiment. In an attempt to understand the biochemical and molecular pathways involved in disease resistance, differentially expressed sequence tags (ESTs) between R and W S. glomerata hemocytes were identified using the PCR technique, suppression subtractive hybridisation (SSH). Sequencing of 300 clones from two SSH libraries revealed 183 distinct sequences of which 113 shared high similarity to sequences in the public databases. Putative function could be assigned to 64 of the sequences. Expression of nine ESTs homologous to genes previously shown to be involved in bivalve immunity was further studied using quantitative reverse-transcriptase PCR (qRT-PCR). The base-line expression of an extracellular superoxide dismutase (ecSOD) and a small heat shock protein (sHsP) were significantly increased, whilst peroxiredoxin 6 (Prx6) and interferon inhibiting cytokine factor (IK) were significantly decreased in R oysters. From these results it was hypothesised that R oysters would be able to generate the anti-parasitic compound, hydrogen peroxide (H(2)O(2)) faster and to higher concentrations during respiratory burst due to the differential expression of genes for the two anti-oxidant enzymes of ecSOD and Prx6. To investigate this hypothesis, protein extracts from hemolymph were analysed for oxidative burst enzyme activity. Analysis of the cell free hemolymph proteins separated by native-polyacrylamide gel electrophoresis (PAGE) failed to detect true superoxide dismutase (SOD) activity by assaying dismutation of superoxide anion in zymograms. However, the ecSOD enzyme appears to generate hydrogen peroxide, presumably via another process, which is yet to be elucidated. This

  13. Transient Co-Expression of Post-Transcriptional Gene Silencing Suppressors for Increased in Planta Expression of a Recombinant Anthrax Receptor Fusion Protein

    Directory of Open Access Journals (Sweden)

    Kittipong Rattanaporn

    2011-08-01

    Full Text Available Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin, CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA domain of human capillary morphogenesis 2 (CMG2, an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG. We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS: p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI, with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

  14. Transient co-expression of post-transcriptional gene silencing suppressors for increased in planta expression of a recombinant anthrax receptor fusion protein.

    Science.gov (United States)

    Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M; McDonald, Karen A

    2011-01-01

    Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

  15. A recombinant pseudorabies virus co-expressing capsid proteins precursor P1-2A of FMDV and VP2 protein of porcine parvovirus: a trivalent vaccine candidate.

    Science.gov (United States)

    Hong, Qi; Qian, Ping; Li, Xiang-Min; Yu, Xiao-Lan; Chen, Huan-Chun

    2007-11-01

    Pseudorabies (PR), foot-and-mouth disease (FMD), and porcine parvovirus disease are three important infectious diseases in swine worldwide. The gene-deleted pseudorabies virus (PRV) has been used as a live-viral vector to develop multivalent genetic engineering vaccine. In this study, a recombinant PRV, which could co-express protein precursor P1-2A of FMDV and VP2 protein of PPV, was constructed using PRV TK(-)/gE(-)/LacZ(+) mutant as the vector. After homologous recombination and plaque purification, recombinant virus PRV TK(-)/gE(-)/P1-2A-VP2 was acquired and identified. Immunogenicity, safety of the recombinant PRV and its protection against PRV were confirmed in a mouse model by indirect ELISA and serum neutralization test. The results show that the recombinant PRV is a candidate vaccine strain to develop a novel trivalent vaccine against PRV, FMDV and PPV in swine.

  16. Differential effects of tango versus Dance for PD in Parkinson disease

    Directory of Open Access Journals (Sweden)

    Marie E McNeely

    2015-12-01

    Full Text Available Over half of the general population does not achieve recommended daily levels of physical activity, and activity levels in people with Parkinson disease (PD are lower than in healthy older adults. Dance can serve as an adjunct to traditional treatments to improve gait, balance, and quality of life in people with PD. This study directly compares a tango dance intervention and a dance intervention based on the Dance for PD model which integrates multiple dance styles. Eleven people with PD participated in a community-based mixed styles dance intervention called Dance for Parkinson’s (D4PD. Participants in the D4PD group were matched to participants in an ongoing community-based exercise study who participated in tango dance. The groups received 12 weeks of intervention, attending one-hour group classes twice a week. Participants were evaluated off anti-PD medication before and after intervention. Measures of balance, repeated sit-to-stand performance and endurance (Mini-BESTest, four square step test, five times sit to stand, six minute walk time improved from pre to post similarly in both groups. Motor sign severity (MDS-UPDRS-III and functional mobility (TUG improved in the tango group and worsened in the D4PD group. Gait velocity was not affected by either intervention. Direct comparisons of different interventions are critical for developing optimal exercise interventions designed to specifically target motor impairments in PD. Tango dance interventions may preferentially improve mobility and motor signs in people with PD, compared to D4PD.

  17. Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Kyung [Department of Radiology, Gachon University Gil Medical Center, Incheon 21565 (Korea, Republic of); Kim, Jeung Sook [Department of Radiology, Dongguk University Ilsan Hospital, Goyang 10326 (Korea, Republic of); Lee, Kyung Won [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Yi, Chin A [Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Koo, Jin Mo [Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Jung, Soon-Hee [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426 (Korea, Republic of)

    2016-11-01

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  18. Multidetector CT findings and differential diagnoses of malignant pleural mesothelioma and metastatic pleural diseases in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Kyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of); Kim, Jeung Sook [Dept. of Radiology, Dongguk University Ilsan Hospital, Goyang (Korea, Republic of); Lee, Kyung Won [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yi, Chin A [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Koo, Jin Mo [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Soon Hee [Dept. of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2016-07-15

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  19. Plant protein and animal proteins: do they differentially affect cardiovascular disease risk?

    Science.gov (United States)

    Richter, Chesney K; Skulas-Ray, Ann C; Champagne, Catherine M; Kris-Etherton, Penny M

    2015-11-01

    Proteins from plant-based compared with animal-based food sources may have different effects on cardiovascular disease (CVD) risk factors. Numerous epidemiologic and intervention studies have evaluated their respective health benefits; however, it is difficult to isolate the role of plant or animal protein on CVD risk. This review evaluates the current evidence from observational and intervention studies, focusing on the specific protein-providing foods and populations studied. Dietary protein is derived from many food sources, and each provides a different composite of nonprotein compounds that can also affect CVD risk factors. Increasing the consumption of protein-rich foods also typically results in lower intakes of other nutrients, which may simultaneously influence outcomes. Given these complexities, blanket statements about plant or animal protein may be too general, and greater consideration of the specific protein food sources and the background diet is required. The potential mechanisms responsible for any specific effects of plant and animal protein are similarly multifaceted and include the amino acid content of particular foods, contributions from other nonprotein compounds provided concomitantly by the whole food, and interactions with the gut microbiome. Evidence to date is inconclusive, and additional studies are needed to further advance our understanding of the complexity of plant protein vs. animal protein comparisons. Nonetheless, current evidence supports the idea that CVD risk can be reduced by a dietary pattern that provides more plant sources of protein compared with the typical American diet and also includes animal-based protein foods that are unprocessed and low in saturated fat. © 2015 American Society for Nutrition.

  20. Differential effects of professional leaders on health care teams in chronic disease management groups.

    Science.gov (United States)

    Wholey, Douglas R; Disch, Joanne; White, Katie M; Powell, Adam; Rector, Thomas S; Sahay, Anju; Heidenreich, Paul A

    2014-01-01

    Leadership by health care professionals is likely to vary because of differences in the social contexts within which they are situated, socialization processes and societal expectations, education and training, and the way their professions define and operationalize key concepts such as teamwork, collaboration, and partnership. This research examines the effect of the nurse and physician leaders on interdependence and encounter preparedness in chronic disease management practice groups. The aim of this study was to examine the effect of complementary leadership by nurses and physicians involved in jointly producing a health care service on care team functioning. The design is a retrospective observational study based on survey data. The unit of analysis is heart failure care groups in U.S. Veterans Health Administration medical centers. Survey and administrative data were collected in 2009 from 68 Veterans Health Administration medical centers. Key variables include nurse and physician leadership, interdependence, psychological safety, coordination, and encounter preparedness. Reliability and validity of survey measures were assessed with exploratory factor analysis and Cronbach alphas. Multivariate analyses tested hypotheses. Professional leadership by nurses and physicians is related to encounter preparedness by different paths. Nurse leadership is associated with greater team interdependence, and interdependence is positively associated with respect. Physician leadership is positively associated with greater psychological safety, respect, and shared goals but is not associated with interdependence. Respect is associated with involvement in learning activities, and shared goals are associated with coordination. Coordination and involvement in learning activities are positively associated with encounter preparedness. By focusing on increasing interdependence and a constructive climate, nurse and physician leaders have the opportunity to increase care coordination

  1. Differential effect of environmental risk factors on postural instability gait difficulties and tremor dominant Parkinson's disease.

    Science.gov (United States)

    Skeie, G O; Muller, B; Haugarvoll, K; Larsen, J P; Tysnes, O B

    2010-09-15

    Both environmental and genetic factors contribute to the development of Parkinson's disease (PD). We have examined environmental risk factors in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. All five neurological wards in the study area of Western Norway participated in the study. A 4-step diagnostic procedure was used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. 212 incident PD patients and 175 age- and gender-matched controls were included. PD patients and controls were asked for information on occupation, education, exposure to pesticides, tobacco, alcohol, and caffeine. Agricultural work was associated with a higher risk of PD (OR 1.75 (1.03-3.0) P = 0.009). There were no differences as to other occupations. Smoking (OR 0.63 (0.42-0.95) P = 0.016) and alcohol use (OR 0.55 P = 0.008) were associated with a lower risk for PD. Interestingly, this inverse association was only seen in postural instability gait difficulties (PIGD) PD (P = 0.046 for smoking, P = 0.07 for alcohol consumption), and not in tremor dominant (TD) PD which was similar to controls. Consumption of coffee was lower in PD patients (3.3 ± 1.8 cups per day vs. 3.8 ± 2.0 in controls P = 0.02). In the regression model including intake of alcohol, coffee, and smoke, only coffee (P = 0.007) and alcohol intake (P = 0.021) remained significant whereas smoking was no longer significant. Thus, it seems as though only coffee intake reduces the risk of PD in general while associations to alcohol and smoking differ between PIGD and TD-PD patients. © 2010 Movement Disorder Society.

  2. Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

    Science.gov (United States)

    Price, J.L.; Yan, Z.; Morris, J.C.; Sheline, Y.I.

    2011-01-01

    Objective: Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level–dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Methods: Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Results: Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Conclusions: Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD. PMID:21525427

  3. Co-expression Network Approach to Studying the Effects of Botulinum Neurotoxin-A.

    Science.gov (United States)

    Mukund, Kavitha; Ward, Samuel R; Lieber, Richard L; Subramaniam, Shankar

    2017-10-16

    Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group 5 with contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within group 5 suggested possible mechanistic roles in recovery from BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin protein content further emphasized the effect of BoNT-A on the sarcomeric contraction machinery in early phase of chemodenervation. In summary, our approach revealed a hierarchical functional response to BoNT-A induced paralysis with early metabolic and later ECM responses and identified putative biomarkers associated with chemodenervation. Additionally, our results provide an unbiased validation of the response documented in our previous workBotulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules

  4. Co-expression of TIMP-1 and its cell surface binding partner CD63 in glioblastomas

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Sørensen, Mia D.; Matos, Ana L.S.A.

    2018-01-01

    scoring. CD63 expression in tumor-associated microglia/macrophages was examined by double-immunofluorescence with ionized calcium-binding adapter molecule 1 (Iba1). The association between CD63 and TIMP-1 was investigated using previously obtained TIMP-1 data from our astrocytoma cohort. Cellular co-expression...... of CD63 was widely distributed in astrocytomas with a significantly increased level in glioblastomas. CD63 levels did not significantly correlate with patient survival at a protein level, and CD63 did not augment the prognostic significance of TIMP-1. Up to 38% of the CD63+ cells expressed Iba1; however......, Iba1 did not appear to impact the prognostic value of CD63. A significant correlation was found between TIMP-1 and CD63, and the TIMP-1 and CD63 proteins were co-expressed at the cellular level and located in close molecular proximity, suggesting that TIMP-1 and CD63 could be co...

  5. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Directory of Open Access Journals (Sweden)

    Recep Colak

    2010-10-01

    Full Text Available Computational prediction of functionally related groups of genes (functional modules from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented.We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB, by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples.We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely

  6. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Science.gov (United States)

    Colak, Recep; Moser, Flavia; Chu, Jeffrey Shih-Chieh; Schönhuth, Alexander; Chen, Nansheng; Ester, Martin

    2010-10-25

    Computational prediction of functionally related groups of genes (functional modules) from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense) regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented. We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB), by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples. We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely available large

  7. An extensive (co-expression analysis tool for the cytochrome P450 superfamily in Arabidopsis thaliana

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    Provart Nicholas J

    2008-04-01

    Full Text Available Abstract Background Sequencing of the first plant genomes has revealed that cytochromes P450 have evolved to become the largest family of enzymes in secondary metabolism. The proportion of P450 enzymes with characterized biochemical function(s is however very small. If P450 diversification mirrors evolution of chemical diversity, this points to an unexpectedly poor understanding of plant metabolism. We assumed that extensive analysis of gene expression might guide towards the function of P450 enzymes, and highlight overlooked aspects of plant metabolism. Results We have created a comprehensive database, 'CYPedia', describing P450 gene expression in four data sets: organs and tissues, stress response, hormone response, and mutants of Arabidopsis thaliana, based on public Affymetrix ATH1 microarray expression data. P450 expression was then combined with the expression of 4,130 re-annotated genes, predicted to act in plant metabolism, for co-expression analyses. Based on the annotation of co-expressed genes from diverse pathway annotation databases, co-expressed pathways were identified. Predictions were validated for most P450s with known functions. As examples, co-expression results for P450s related to plastidial functions/photosynthesis, and to phenylpropanoid, triterpenoid and jasmonate metabolism are highlighted here. Conclusion The large scale hypothesis generation tools presented here provide leads to new pathways, unexpected functions, and regulatory networks for many P450s in plant metabolism. These can now be exploited by the community to validate the proposed functions experimentally using reverse genetics, biochemistry, and metabolic profiling.

  8. FastGCN: a GPU accelerated tool for fast gene co-expression networks.

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    Meimei Liang

    Full Text Available Gene co-expression networks comprise one type of valuable biological networks. Many methods and tools have been published to construct gene co-expression networks; however, most of these tools and methods are inconvenient and time consuming for large datasets. We have developed a user-friendly, accelerated and optimized tool for constructing gene co-expression networks that can fully harness the parallel nature of GPU (Graphic Processing Unit architectures. Genetic entropies were exploited to filter out genes with no or small expression changes in the raw data preprocessing step. Pearson correlation coefficients were then calculated. After that, we normalized these coefficients and employed the False Discovery Rate to control the multiple tests. At last, modules identification was conducted to construct the co-expression networks. All of these calculations were implemented on a GPU. We also compressed the coefficient matrix to save space. We compared the performance of the GPU implementation with those of multi-core CPU implementations with 16 CPU threads, single-thread C/C++ implementation and single-thread R implementation. Our results show that GPU implementation largely outperforms single-thread C/C++ implementation and single-thread R implementation, and GPU implementation outperforms multi-core CPU implementation when the number of genes increases. With the test dataset containing 16,000 genes and 590 individuals, we can achieve greater than 63 times the speed using a GPU implementation compared with a single-thread R implementation when 50 percent of genes were filtered out and about 80 times the speed when no genes were filtered out.

  9. Inferring the transcriptional landscape of bovine skeletal muscle by integrating co-expression networks.

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    Nicholas J Hudson

    Full Text Available BACKGROUND: Despite modern technologies and novel computational approaches, decoding causal transcriptional regulation remains challenging. This is particularly true for less well studied organisms and when only gene expression data is available. In muscle a small number of well characterised transcription factors are proposed to regulate development. Therefore, muscle appears to be a tractable system for proposing new computational approaches. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a simple algorithm that asks "which transcriptional regulator has the highest average absolute co-expression correlation to the genes in a co-expression module?" It correctly infers a number of known causal regulators of fundamental biological processes, including cell cycle activity (E2F1, glycolysis (HLF, mitochondrial transcription (TFB2M, adipogenesis (PIAS1, neuronal development (TLX3, immune function (IRF1 and vasculogenesis (SOX17, within a skeletal muscle context. However, none of the canonical pro-myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6 and MEF2C were linked to muscle structural gene expression modules. Co-expression values were computed using developing bovine muscle from 60 days post conception (early foetal to 30 months post natal (adulthood for two breeds of cattle, in addition to a nutritional comparison with a third breed. A number of transcriptional landscapes were constructed and integrated into an always correlated landscape. One notable feature was a 'metabolic axis' formed from glycolysis genes at one end, nuclear-encoded mitochondrial protein genes at the other, and centrally tethered by mitochondrially-encoded mitochondrial protein genes. CONCLUSIONS/SIGNIFICANCE: The new module-to-regulator algorithm complements our recently described Regulatory Impact Factor analysis. Together with a simple examination of a co-expression module's contents, these three gene expression approaches are starting to illuminate the in vivo

  10. Limited role of I-123 IPT SPECT in differentiating essential tremor from early stage of Parkinson's disease

    International Nuclear Information System (INIS)

    Yoo, Y. H.; Yoon, M. J.; Lee, J. D.; Kim, J. H.; Lee, E.; Kim, H. S.; Choi, T. H.

    2002-01-01

    The study was to assess clinically applicable cut-off value in differential diagnosis among early stage of Parkinson's disease(PD) and essential tremor(ET) and normal control(NL) groups on I-123 IPT SPECT using dual head gamma camera both quantitatively and qualitatively. 50 NL (mean age 27.9), 20 early PD patients (mean age 58.2), 30 advanced PD patients (mean age 63.1) and 20 ET patients (mean age 39.9) were included and performed brain SPECT 2 hours after administration of I-123 IPT using dual head gamma camera. Recostructed SPECT data were assessed for specific/nonspecific binding ratio of striatum using (RBG-OCC/OCC, LBG-OCC/OCC) ratio. RBG-OCC/OCC and LBG-OCC/OCC ratio was decreased with increasing grade of H-Y stage in PD. Mean value of specific/nonspecific binding ratio was significantly different between advanced PD group and NL group. However, significant overlap of striatal specific/nonspecific bonding ratio were observed between early PD group and ET group. Suggested cut-off value of striatal binding ratio which can diagnose PD would be 2.1. Although I-123 IPT SPECT may be a useful method for the diagnosis of advanced PD and objective evaluation of progress of clinical stages, care should be made in the differential diagnosis of subclinical and early stage of PD and other motor distubances mimicking PD such as ET in view of significant overlap in striatal I-123 IPT specific/nonspecific binding ratio

  11. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean) Cattle.

    Science.gov (United States)

    Lim, Dajeong; Lee, Seung-Hwan; Kim, Nam-Kuk; Cho, Yong-Min; Chai, Han-Ha; Seong, Hwan-Hoo; Kim, Heebal

    2013-01-01

    Marbling (intramuscular fat) is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the 'marbling score' trait and systemically analyzed the network topology in Hanwoo (Korean cattle). As a result, we determined 3 modules (gene groups) that showed statistically significant results for marbling score. In particular, one module (denoted as red) has a statistically significant result for marbling score (p = 0.008) and intramuscular fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA) have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  12. Large clusters of co-expressed genes in the Drosophila genome.

    Science.gov (United States)

    Boutanaev, Alexander M; Kalmykova, Alla I; Shevelyov, Yuri Y; Nurminsky, Dmitry I

    2002-12-12

    Clustering of co-expressed, non-homologous genes on chromosomes implies their co-regulation. In lower eukaryotes, co-expressed genes are often found in pairs. Clustering of genes that share aspects of transcriptional regulation has also been reported in higher eukaryotes. To advance our understanding of the mode of coordinated gene regulation in multicellular organisms, we performed a genome-wide analysis of the chromosomal distribution of co-expressed genes in Drosophila. We identified a total of 1,661 testes-specific genes, one-third of which are clustered on chromosomes. The number of clusters of three or more genes is much higher than expected by chance. We observed a similar trend for genes upregulated in the embryo and in the adult head, although the expression pattern of individual genes cannot be predicted on the basis of chromosomal position alone. Our data suggest that the prevalent mechanism of transcriptional co-regulation in higher eukaryotes operates with extensive chromatin domains that comprise multiple genes.

  13. Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

    Science.gov (United States)

    Han, Xinxin; Yin, Linlin; Xue, Hongwei

    2012-07-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

  14. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Dajeong Lim

    2013-01-01

    Full Text Available Marbling (intramuscular fat is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the ‘marbling score’ trait and systemically analyzed the network topology in Hanwoo (Korean cattle. As a result, we determined 3 modules (gene groups that showed statistically significant results for marbling score. In particular, one module (denoted as red has a statistically significant result for marbling score (p = 0.008 and intramuscular fat (p = 0.02 and water capacity (p = 0.006. From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  15. Differentiation of dementia with lewy bodies from Alzheimer's disease using FDG PET and I-123-fluoropropyl-β-CIT SPECT

    International Nuclear Information System (INIS)

    Park, Eun Kyung; Cho, Sang Soo; Lee, Jae Sung; Kim, Jung Eun; Kim, Sang Yun; Lee, Won Woo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2004-01-01

    Dementia with Lewy bodies (DLB) shares clinical and pathological features with Alzheimer's disease (AD) and Parkinson's disease. The differentiation of DLB from these disorders poses difficulties. We compared regional cerebral metabolic impairment and dopaminergic neuronal integrity between patients with DLB and AD using FDG PET and I-123-fluoropropyl-β-CIT (FP-CIT) SPECT, respectively, as measures for differential diagnosis. Fourteen clinically diagnosed DLB patients, 15 probable AD patients, and 12 age- and gender-matched healthy controls were studied with FDG PET and FP-CIT SPECT. A voxel-wise comparison of PET images was performed using SPM99. A dopamine transporter (DAT) parameter V3 was calculated in striatal regions as (striatal VOIcerebellar VOI)/cerebellar VOI activity on SPECT images obtained 3 h after injection of 185 MBq FP-CIT. SPM analysis of PET images of DLB revealed hypometabolism bilaterally in the occipital cortices, lateral occipitotemporal gyri, cunei, caudate, and Thalami compared with controls, most pronounced in the occipital cortex compared with AD. In DLB, V3 in the caudate (1.07±0.55) and putamen (1.01±0.34) was significantly (P < 0.001) lower than in AD (2.73±0.75 and 3.17±0.88, respectively) and controls (3.00±0.45 and 3.11±0.31, respectively). There was no significant difference in striatal V3 between AD and controls. The ratio of putamen-to-caudate V3 was not significantly different between DLB (1.04±0.32) and controls (1.05±0.12), indicating that DATs in the caudate and putamen are evenly affected in DLB. In DLB, there was a significant correlation between striatal V3 and MMSE score (rho=0.97, P<0.01). These data demonstrate different biochemical features between DLB and AD, in terms of regional brain metabolism and dopaminergic neuronal integrity. Measures of the glucose metabolism in the occipital cortex and the striatal DAT density may be informative diagnostic aids to distinguish DLB from AD

  16. Detection of a new submicroscopic Norrie disease deletion interval with a novel DNA probe isolated by differential Alu PCR fingerprint cloning

    NARCIS (Netherlands)

    Bergen, A. A.; Wapenaar, M. C.; Schuurman, E. J.; Diergaarde, P. J.; Lerach, H.; Monaco, A. P.; Bakker, E.; Bleeker-Wagemakers, E. M.; van Ommen, G. J.

    1993-01-01

    Differential Alu PCR fingerprint cloning was used to isolate a DNA probe from the Xp11.4-->p11.21 region of the human X chromosome. This novel sequence, cpXr318 (DXS742), detects a new submicroscopic deletion interval at the Norrie disease locus (NDP). Combining our data with the consensus genetic

  17. Masked assessment of MRI findings: is it possible to differentiate neuro-Behcet`s disease from other central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Coban, O.; Bahar, S.; Akman-Demir, G.; Tasci, B.; Serdaroglu, P. [Univ. of Istanbul (Turkey). Dept. of Neurology; Yurdakul, S.; Yazici, H. [Univ. of Istanbul (Turkey). Dept. of Internal Medicine

    1999-04-01

    Two neuroradiologists reviewed MRI studies of 34 patients with neuro-Behcet`s disease (NBD), 22 with multiple sclerosis (MS) and 7 with systemic lupus erythematosus (SLE) with central nervous system involvement, masked to the clinical diagnosis, age and sex of the patients. Of the patients with NBD 12 were in an acute attack; the others had chronic disease. MRI was assessed using a set of criteria, looking at atrophy, the site of discrete parenchymal lesions, regions of predominant involvement and the extent of the lesion(s). The observers also made a guess at the clinical diagnosis. The brain stem and/or basal ganglia were the most predominantly involved sites in all patients with acute NBD; 75 % of these lesions were large and confluent, mainly extending from the brain stem to the diencephalon and basal ganglia. However, in chronic cases, the predominant involvement was in the brain stem and/or basal ganglia in only 36 %, and in cerebral hemisphere white matter in another 36 %; 27 % of these patients showed no parenchymal lesion. Hemisphere white-matter lesions were equally distributed between periventricular and other areas in NBD, while in MS more were periventricular, and in SLE more were nonperiventricular. Brain-stem atrophy was seen in 21 % of patients with NBD, with a specificity of 96.5 %. In the absence of cortical atrophy, its specificity was 100 %. The attempt at making a radiological diagnosis was successful in all cases of acute NBD and 95.5 % of patients with MS, but in only 40 % of patients with chronic NBD. Most of this latter groups MRI studies were interpreted as MS. An extensive lesion involving the brain stem and basal ganglia seemed to be diagnostic of acute NBD. However, hemisphere white-matter lesions could not be differentiated from those in MS. (orig.) With 3 figs., 6 tabs., 18 refs.

  18. Serum 25-Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases.

    Directory of Open Access Journals (Sweden)

    Donghyun Jee

    Full Text Available To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES, and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD, diabetic retinopathy (DR, cataract, and DES.A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies.The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55-1.30, P for trend = 0.076 after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30-1.64 and cataract (OR = 0.76, 95% CI: 0.59-0.99 were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18-0.76 and late AMD (OR = 0.32, 95% CI: 0.12-0.81 were lower in men.The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES.

  19. Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson’s Disease

    Science.gov (United States)

    Hossein-nezhad, Arash; Fatemi, Roya Pedram; Ahmad, Rili; Peskind, Elaine R.; Zabetian, Cyrus P.; Hu, Shu-Ching; Shi, Min; Wahlestedt, Claes; Zhang, Jing; Faghihi, Mohammad Ali

    2016-01-01

    Background: Parkinson’s disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time. Objective: We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers. Methods: Small volumes of CSF from 27 PD patients and 30 healthy age- and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT-PCR). Results: A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5,PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva.4 (close to the LRRK2 gene locus), as potential PD biomarkers. Conclusions: The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes. PMID:26889637

  20. Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases

    Science.gov (United States)

    Li, W; Chen, Y-T; Hayashida, Y; Blanco, G; Kheirkah, A; He, H; Chen, S-Y; Liu, C-Y; Tseng, SCG

    2010-01-01

    Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens–Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP–Pax6 transgenes into these Pax6− clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium. PMID:18027901

  1. Once for All: A Novel Robust System for Co-expression of Multiple Chimeric Fluorescent Fusion Proteins in Plants

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    Guitao Zhong

    2017-06-01

    Full Text Available Chimeric fluorescent fusion proteins have been employed as a powerful tool to reveal the subcellular localizations and dynamics of proteins in living cells. Co-expression of a fluorescent fusion protein with well-known organelle markers in the same cell is especially useful in revealing its spatial and temporal functions of the protein in question. However, the conventional methods for co-expressing multiple fluorescent tagged proteins in plants have the drawbacks of low expression efficiency, variations in the expression level and time-consuming genetic crossing. Here, we have developed a novel robust system that allows for high-efficient co-expression of multiple chimeric fluorescent fusion proteins in plants in a time-saving fashion. This system takes advantage of employing a single expression vector which consists of multiple semi-independent expressing cassettes for the protein co-expression thereby overcoming the limitations of using multiple independent expressing plasmids. In addition, it is a highly manipulable DNA assembly system, in which modification and recombination of DNA molecules are easily achieved through an optimized one-step assembly reaction. By employing this effective system, we demonstrated that co-expression of two chimeric fluorescent fusion reporter proteins of vacuolar sorting receptor and secretory carrier membrane protein gave rise to their perspective subcellular localizations in plants via both transient expression and stable transformation. Thus, we believed that this technical advance represents a promising approach for multi-color-protein co-expression in plant cells.

  2. Identification and analysis of differential miRNAs in PK-15 cells after foot-and-mouth disease virus infection.

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    Ke-Shan Zhang

    Full Text Available The alterations of MicroRNAs(miRNAs in host cell after foot-and-mouth disease virus (FMDV infection is still obscure. To increase our understanding of the pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high-throu MicroRNAs (miRNAs play an important role both in the post-transcriptional regulation of gene expression and host-virus interactions. Despite investigations of miRNA expression ghput sequencing and bioinformatic tools were used to identify differentially expressed miRNAs and analyze their functions during FMDV infection of PK-15 cells. Results indicated that 9,165,674 and 9,230,378 clean reads were obtained, with 172 known and 72 novel miRNAs differently expressed in infected and uninfected groups respectively. Some of differently expressed miRNAs were validated using stem-loop real-time quantitative RT-PCR. The GO annotation and KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in immune response and cell death pathways.

  3. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Science.gov (United States)

    Xiao, Xiaolin; Moreno-Moral, Aida; Rotival, Maxime; Bottolo, Leonardo; Petretto, Enrico

    2014-01-01

    Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co-expressed

  4. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    Directory of Open Access Journals (Sweden)

    Xiaolin Xiao

    2014-01-01

    Full Text Available Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states. Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based and humans (mRNA-sequencing-based and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi

  5. S187. SEARCHING FOR BRAIN CO-EXPRESSION MODULES THAT CONTRIBUTE DISPROPORTIONATELY TO THE COMMON POLYGENIC RISK FOR SCHIZOPHRENIA

    Science.gov (United States)

    Costas, Javier; Paramo, Mario; Arrojo, Manuel

    2018-01-01

    Abstract Background Genomic research has revealed that schizophrenia is a highly polygenic disease. Recent estimates indicate that at least 71% of genomic segments of 1 Mb include one or more risk loci for schizophrenia (Loh et al., Nature Genet 2015). This extremely high polygenicity represents a challenge to decipher the biological basis of schizophrenia, as it is expected that any set of SNPs with enough size will be associated with the disorder. Among the different gene sets available for study (such as those from Gene Ontology, KEGG pathway, Reactome pathways or protein protein interaction datasets), those based on brain co-expression networks represent putative functional relationships in the relevant tissue. The aim of this work was to identify brain co-expression networks that contribute disproportionately to the common polygenic risk for schizophrenia to get more insight on schizophrenia etiopathology. Methods We analyzed a case -control dataset consisting of 582 schizophrenia patients from Galicia, NW Spain, and 591 ancestrally matched controls, genotyped with the Illumina PsychArray. Using as discovery sample the summary results from the largest GWAS of schizophrenia to date (Psychiatric Genomics Consortium, SCZ2), we generated polygenic risk scores (PRS) in our sample based on SNPs located at genes belonging to brain co-expression modules determined by the CommonMind Consortium (Fromer et al., Nature Neurosci 2016). PRS were generated using the clumping procedure of PLINK, considering several different thresholds to select SNPs from the discovery sample. In order to test if any specific module increased risk to schizophrenia more than expected by their size, we generated up to 10,000 random permutations of the same number of SNPs, matched by frequency, distance to nearest gene, number of SNPs in LD and gene density, using SNPsnap. Results As expected, most modules with enough number of independent SNPs belonging to them showed a significant increase in

  6. Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases.

    Science.gov (United States)

    Kline, Rachel A; Kaifer, Kevin A; Osman, Erkan Y; Carella, Francesco; Tiberi, Ariana; Ross, Jolill; Pennetta, Giuseppa; Lorson, Christian L; Murray, Lyndsay M

    2017-03-01

    The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers

  7. Aberrant Levels of Hematopoietic/Neuronal Growth and Differentiation Factors in Euthyroid Women at Risk for Autoimmune Thyroid Disease.

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    Elske T Massolt

    Full Text Available Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects.We studied 64 TPO-Ab-negative females with at least 1 first- or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs. We measured serum levels of brain-derived neurotrophic factor (BDNF, Stem Cell Factor (SCF, Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2, Epidermal Growth Factor (EGF and IL-7 at baseline.BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001, while EGF (506.9 vs 307.6 pg/ml, P = 0.003 and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028 were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017. In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1β, IL-6 and CCL-3, of which high levels also preceded seroconversion.Relatives of AITD patients show aberrant serum levels of 4 hematopoietic/neuronal growth factors similar to the aberrancies found in mood disorder patients, suggesting that shared growth and differentiation defects in both the hematopoietic and neuronal system may underlie thyroid autoimmunity and mood disorders. A

  8. Neuropsychological Testing in Pathologically Verified Alzheimer Disease and Frontotemporal Dementia: How Well Do the Uniform Data Set Measures Differentiate Between Diseases?

    Science.gov (United States)

    Ritter, Aaron R; Leger, Gabriel C; Miller, Justin B; Banks, Sarah J

    2017-01-01

    Differences in cognition between frontotemporal dementia (FTD) and Alzheimer disease (AD) are well described in clinical cohorts, but have rarely been confirmed in studies with pathologic verification. For emerging therapeutics to succeed, determining underlying pathology early in the disease course is increasingly important. Neuropsychological evaluation is an important component of the diagnostic workup for AD and FTD. Patients with FTD are thought to have greater deficits in language and executive function while patients with AD are more likely to have deficits in memory. To determine if performance on initial cognitive testing can reliably distinguish between patients with frontotemporal lobar degeneration (FTLD) and AD neuropathology. In addition, are there other factors of the neuropsychological assessment that can be used to enhance the accuracy of underlying pathology? Using a logistic regression we retrospectively compared neurocognitive performance on initial evaluation of 106 patients with pathologically verified FTLD (pvFTLD), with 558 pathologically verified AD (pvAD) patients from the National Alzheimer's Coordinating Center using data from the Uniform Data Set (UDS) and the neuropathology data set. As expected, pvFTLD patients were younger, demonstrated better memory performance, and had more neuropsychiatric symptoms than pvAD patients. Other results were less predictable: pvFTLD patients performed better on one test of executive function (trail making test part B) but worse on another (digit span backward). Performance on language testing did not strongly distinguish the 2 groups. To determine what factors led to a misdiagnosis of AD in patients with FTLD, we further analyzed a small group of pvFTLD patients. These patients demonstrated older age and lower Neuropsychiatric Inventory Questionnaire counts compared with accurately diagnosed cases. Other than memory, numerical scores of neurocognitive performance on the UDS are of limited value in

  9. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

    Directory of Open Access Journals (Sweden)

    Michael S Stalvey

    Full Text Available Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF. CF-related bone disease (CFBD is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR, the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/- mouse model. In the murine calvarial organ culture assay, Cftr-/- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+ littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-κB ligand (Rankl mRNA was detected, significantly less osteoprotegerin (Opg was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH-stimulated canonical Wnt

  10. Differential Contributions of Selective Attention and Sensory Integration to Driving Performance in Healthy Aging and Alzheimer's Disease.

    Science.gov (United States)

    Venkatesan, Umesh M; Festa, Elena K; Ott, Brian R; Heindel, William C

    2018-05-01

    Patients with Alzheimer's disease (AD) demonstrate deficits in cross-cortical feature binding distinct from age-related changes in selective attention. This may have consequences for driving performance given its demands on multisensory integration. We examined the relationship of visuospatial search and binding to driving in patients with early AD and elderly controls (EC). Participants (42 AD; 37 EC) completed search tasks requiring either luminance-motion (L-M) or color-motion (C-M) binding, analogs of within and across visual processing stream binding, respectively. Standardized road test (RIRT) and naturalistic driving data (CDAS) were collected alongside clinical screening measures. Patients performed worse than controls on most cognitive and driving indices. Visual search and clinical measures were differentially related to driving behavior across groups. L-M search and Trail Making Test (TMT-B) were associated with RIRT performance in controls, while C-M binding, TMT-B errors, and Clock Drawing correlated with CDAS performance in patients. After controlling for demographic and clinical predictors, L-M reaction time significantly predicted RIRT performance in controls. In patients, C-M binding made significant contributions to CDAS above and beyond demographic and clinical predictors. RIRT and C-M binding measures accounted for 51% of variance in CDAS performance in patients. Whereas selective attention is associated with driving behavior in EC, cross-cortical binding appears most sensitive to driving in AD. This latter relationship may emerge only in naturalistic settings, which better reflect patients' driving behavior. Visual integration may offer distinct insights into driving behavior, and thus has important implications for assessing driving competency in early AD. (JINS, 2018, 24, 486-497).

  11. Use of intraoperative local field potential spectral analysis to differentiate basal ganglia structures in Parkinson's disease patients.

    Science.gov (United States)

    Kolb, Rachel; Abosch, Aviva; Felsen, Gidon; Thompson, John A

    2017-06-01

    Identification of brain structures traversed during implantation of deep brain-stimulating (DBS) electrodes into the subthalamic nucleus (STN-DBS) for the treatment of Parkinson's disease (PD) frequently relies on subjective correspondence between kinesthetic response and multiunit activity. However, recent work suggests that local field potentials (LFP) could be used as a more robust signal to objectively differentiate subcortical structures. The goal of this study was to analyze the spectral properties of LFP collected during STN-DBS in order to objectively identify commonly traversed brain regions and improve our understanding of aberrant oscillations in the PD-related pathophysiological cortico-basal ganglia network. In 21 PD patients, LFP were collected and analyzed during STN-DBS implantation surgery. Spectral power for delta-, theta-, alpha-, low-beta-, and high-beta-frequency bands was assessed at multiple depths throughout the subcortical structures traversed on the trajectory to the ventral border of STN. Similar to previous findings, beta-band oscillations had an increased magnitude within the borders of the motor-related area of STN, however, across several subjects, we also observed increased high-beta magnitude within the borders of thalamus. Comparing across all patients using relative power, we observed a gradual increase in the magnitude of both low- and high-beta-frequency bands as the electrode descended from striatum to STN. These results were also compared with frequency bands below beta, and similar trends were observed. Our results suggest that LFP signals recorded during the implantation of a DBS electrode evince distinct oscillatory signatures that distinguish subcortical structures. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  12. Performance of the 4-mg intravenous dexamethasone suppression test in differentiating Cushing disease from pseudo-Cushing syndrome.

    Science.gov (United States)

    Nouvel, Migueline; Rabilloud, Muriel; Raverot, Véronique; Subtil, Fabien; Vouillarmet, Julien; Thivolet, Charles; Jouanneau, Emmanuel; Borson-Chazot, Françoise; Pugeat, Michel; Raverot, Gérald

    2016-02-01

    Discriminating Cushing disease (CD) from pseudo-Cushing syndrome (PCS) is a challenging task that may be overcome with the 4-mg intravenous (IV) dexamethasone suppression test (DST). Assess the performance of the 4-mg IV DST in the differential diagnosis between CD and PCS in well-characterized patients. Retrospective comparative study of subjects seen in a tertiary care unit (November 2008 to July 2011). Thirty-six patients with PCS and 32 patients with CD underwent 4-mg IV dexamethasone infusions from 11 am to 3 pm. Areas Under ROC Curves (AUCs) were estimated and compared for ACTH and cortisol measured at 4 pm the same day (day 1) and 8 am the next day (day 2). The ROC curve of the marker with the highest AUC was used to determine the threshold with the highest specificity for 100% sensitivity. The AUC of ACTH at 8 am on day 2 was estimated at 98.4% (95% CI: [92.1-100]), which is significantly greater than that of ACTH at 4 pm on day 1 (P=0.04) and that of cortisol at 8 am on day 2 (P=0.05). For ACTH at 8 am on day 2, the threshold with the highest specificity for 100% sensitivity was estimated at 14.8 ng/L. At this threshold, the sensitivity was estimated at 100% [89-100] and the specificity at 83.3% [67-94]. The 4-mg IV DST is an easy and accurate tool in distinguishing CD from PCS. It deserves thus a better place in establishing the diagnosis of CD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer’s disease model cell line

    International Nuclear Information System (INIS)

    Sung, Hye Youn; Choi, Eun Nam; Ahn Jo, Sangmee; Oh, Seikwan; Ahn, Jung-Hyuck

    2011-01-01

    Highlights: ► Genome-wide DNA methylation pattern in Alzheimer’s disease model cell line. ► Integrated analysis of CpG methylation and mRNA expression profiles. ► Identify three Swedish mutant target genes; CTIF, NXT2 and DDR2 gene. ► The effect of Swedish mutation on alteration of DNA methylation and gene expression. -- Abstract: The Swedish mutation of amyloid precursor protein (APP-sw) has been reported to dramatically increase beta amyloid production through aberrant cleavage at the beta secretase site, causing early-onset Alzheimer’s disease (AD). DNA methylation has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-sw-mediated epigenetic alterations in AD pathogenesis remains largely unknown. We analyzed genome-wide interplay between promoter CpG DNA methylation and gene expression in an APP-sw-expressing AD model cell line. To identify genes whose expression was regulated by DNA methylation status, we performed integrated analysis of CpG methylation and mRNA expression profiles, and identified three target genes of the APP-sw mutant; hypomethylated CTIF (CBP80/CBP20-dependent translation initiation factor) and NXT2 (nuclear exporting factor 2), and hypermethylated DDR2 (discoidin domain receptor 2). Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored mRNA expression of these three genes, implying methylation-dependent transcriptional regulation. The profound alteration in the methylation status was detected at the −435, −295, and −271 CpG sites of CTIF, and at the −505 to −341 region in the promoter of DDR2. In the promoter region of NXT2, only one CpG site located at −432 was differentially unmethylated in APP-sw cells. Thus, we demonstrated the effect of the APP-sw mutation on alteration of DNA methylation and subsequent gene expression. This epigenetic regulatory mechanism may contribute to the pathogenesis of AD.

  14. Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

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    Arnett Donna

    2009-08-01

    Full Text Available Abstract Background Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years and compared them to similarly aged non-Hispanic whites (NHW (n = 597. Results Minor allele frequency (MAF distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only. Conclusion These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.

  15. Effects of threshold on the topology of gene co-expression networks.

    Science.gov (United States)

    Couto, Cynthia Martins Villar; Comin, César Henrique; Costa, Luciano da Fontoura

    2017-09-26

    Several developments regarding the analysis of gene co-expression profiles using complex network theory have been reported recently. Such approaches usually start with the construction of an unweighted gene co-expression network, therefore requiring the selection of a suitable threshold defining which pairs of vertices will be connected. We aimed at addressing such an important problem by suggesting and comparing five different approaches for threshold selection. Each of the methods considers a respective biologically-motivated criterion for electing a potentially suitable threshold. A set of 21 microarray experiments from different biological groups was used to investigate the effect of applying the five proposed criteria to several biological situations. For each experiment, we used the Pearson correlation coefficient to measure the relationship between each gene pair, and the resulting weight matrices were thresholded considering several values, generating respective adjacency matrices (co-expression networks). Each of the five proposed criteria was then applied in order to select the respective threshold value. The effects of these thresholding approaches on the topology of the resulting networks were compared by using several measurements, and we verified that, depending on the database, the impact on the topological properties can be large. However, a group of databases was verified to be similarly affected by most of the considered criteria. Based on such results, it can be suggested that when the generated networks present similar measurements, the thresholding method can be chosen with greater freedom. If the generated networks are markedly different, the thresholding method that better suits the interests of each specific research study represents a reasonable choice.

  16. Enforcing Co-expression Within a Brain-Imaging Genomics Regression Framework.

    Science.gov (United States)

    Zille, Pascal; Calhoun, Vince D; Wang, Yu-Ping

    2017-06-28

    Among the challenges arising in brain imaging genetic studies, estimating the potential links between neurological and genetic variability within a population is key. In this work, we propose a multivariate, multimodal formulation for variable selection that leverages co-expression patterns across various data modalities. Our approach is based on an intuitive combination of two widely used statistical models: sparse regression and canonical correlation analysis (CCA). While the former seeks multivariate linear relationships between a given phenotype and associated observations, the latter searches to extract co-expression patterns between sets of variables belonging to different modalities. In the following, we propose to rely on a 'CCA-type' formulation in order to regularize the classical multimodal sparse regression problem (essentially incorporating both CCA and regression models within a unified formulation). The underlying motivation is to extract discriminative variables that are also co-expressed across modalities. We first show that the simplest formulation of such model can be expressed as a special case of collaborative learning methods. After discussing its limitation, we propose an extended, more flexible formulation, and introduce a simple and efficient alternating minimization algorithm to solve the associated optimization problem.We explore the parameter space and provide some guidelines regarding parameter selection. Both the original and extended versions are then compared on a simple toy dataset and a more advanced simulated imaging genomics dataset in order to illustrate the benefits of the latter. Finally, we validate the proposed formulation using single nucleotide polymorphisms (SNP) data and functional magnetic resonance imaging (fMRI) data from a population of adolescents (n = 362 subjects, age 16.9 ± 1.9 years from the Philadelphia Neurodevelopmental Cohort) for the study of learning ability. Furthermore, we carry out a significance

  17. Network statistics of genetically-driven gene co-expression modules in mouse crosses

    Directory of Open Access Journals (Sweden)

    Marie-Pier eScott-Boyer

    2013-12-01

    Full Text Available In biology, networks are used in different contexts as ways to represent relationships between entities, such as for instance interactions between genes, proteins or metabolites. Despite progress in the analysis of such networks and their potential to better understand the collective impact of genes on complex traits, one remaining challenge is to establish the biologic validity of gene co-expression networks and to determine what governs their organization. We used WGCNA to construct and analyze seven gene expression datasets from several tissues of mouse recombinant inbred strains (RIS. For six out of the 7 networks, we found that linkage to module QTLs (mQTLs could be established for 29.3% of gene co-expression modules detected in the several mouse RIS. For about 74.6% of such genetically-linked modules, the mQTL was on the same chromosome as the one contributing most genes to the module, with genes originating from that chromosome showing higher connectivity than other genes in the modules. Such modules (that we considered as genetically-driven had network statistic properties (density, centralization and heterogeneity that set them apart from other modules in the network. Altogether, a sizeable portion of gene co-expression modules detected in mouse RIS panels had genetic determinants as their main organizing principle. In addition to providing a biologic interpretation validation for these modules, these genetic determinants imparted on them particular properties that set them apart from other modules in the network, to the point that they can be predicted to a large extent on the basis of their network statistics.

  18. Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Lauren A Vanderlinden

    Full Text Available To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA. Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL with a genomic region that regulates alcohol consumption (bQTL. To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we compared candidate coexpression modules from whole brain gene expression data (gathered with Affymetrix 430 v2 arrays in the Colorado laboratories and from gene expression data from 6 brain regions (nucleus accumbens (NA; prefrontal cortex (PFC; ventral tegmental area (VTA; striatum (ST; hippocampus (HP; cerebellum (CB available from GeneNetwork. The candidate modules were used to construct candidate eigengene networks across brain regions, resulting in three "meta-modules", composed of candidate modules from two or more brain regions (NA, PFC, ST, VTA and whole brain. To mitigate the potential influence of chromosomal location of transcripts and cis-eQTLs in linkage disequilibrium, we calculated a semi-partial correlation of the transcripts in the meta-modules with alcohol consumption conditional on the transcripts' cis-eQTLs. The function of transcripts that retained the correlation with the phenotype after correction for the strong genetic influence, implicates processes of protein metabolism in the ER and Golgi as influencing susceptibility to variation in alcohol consumption. Integration of these data with human GWAS provides further information on the function of polymorphisms associated with alcohol-related traits.

  19. Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

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    Xiao Chang

    Full Text Available BACKGROUND: The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. METHODOLOGY/PRINCIPAL FINDINGS: In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A, and secondary metabolism is induced when the growth is slowed down (phase B. Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. CONCLUSIONS: This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies

  20. Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

    Science.gov (United States)

    Chang, Xiao; Liu, Shuai; Yu, Yong-Tao; Li, Yi-Xue; Li, Yuan-Yuan

    2010-08-12

    The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms.

  1. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease -- can it differentiate bone infarcts from acute osteomyelitis?

    Science.gov (United States)

    Delgado, Jorge; Bedoya, Maria A; Green, Abby M; Jaramillo, Diego; Ho-Fung, Victor

    2015-12-01

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children.

  2. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    International Nuclear Information System (INIS)

    Delgado, Jorge; Bedoya, Maria A.; Green, Abby M.; Jaramillo, Diego; Ho-Fung, Victor

    2015-01-01

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  3. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Jorge; Bedoya, Maria A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Green, Abby M. [The Children' s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA (United States); Jaramillo, Diego; Ho-Fung, Victor [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States)

    2015-12-15

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  4. Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yingjia [School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600 (China); Gao, Zhong [Department of Interventional Therapy, Dalian Municipal Central Hospital, Dalian 116033 (China); Liang, Wenbo [Medical College of Dalian University, Dalian 116600, Liaoning (China); Kong, Liang; Jiao, Yanan; Li, Shaoheng; Tao, Zhenyu; Yan, Yuhui [School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600 (China); Yang, Jingxian, E-mail: jingxianyang@yahoo.com [School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600 (China)

    2015-12-15

    Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)β peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aβ protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effects that were exerted via activation of Wnt/β-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders. - Highlights: • An Alzheimer's disease model was successfully established by transfecting APP gene into neural stem cells in vitro. • Roles of osthole in experimental AD cells were studied. • Osthole promotes proliferation and differentiation into neurons and inhibits accumulation of Aβ{sub 1–42} peptide and apoptosis. • Osthole exerts protection via Wnt/β-catenin signaling pathway.

  5. Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model

    International Nuclear Information System (INIS)

    Yao, Yingjia; Gao, Zhong; Liang, Wenbo; Kong, Liang; Jiao, Yanan; Li, Shaoheng; Tao, Zhenyu; Yan, Yuhui; Yang, Jingxian

    2015-01-01

    Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)β peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aβ protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effects that were exerted via activation of Wnt/β-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders. - Highlights: • An Alzheimer's disease model was successfully established by transfecting APP gene into neural stem cells in vitro. • Roles of osthole in experimental AD cells were studied. • Osthole promotes proliferation and differentiation into neurons and inhibits accumulation of Aβ 1–42 peptide and apoptosis. • Osthole exerts protection via Wnt/β-catenin signaling pathway.

  6. Coexpression landscape in ATTED-II: usage of gene list and gene network for various types of pathways.

    Science.gov (United States)

    Obayashi, Takeshi; Kinoshita, Kengo

    2010-05-01

    Gene coexpression analyses are a powerful method to predict the function of genes and/or to identify genes that are functionally related to query genes. The basic idea of gene coexpression analyses is that genes with similar functions should have similar expression patterns under many different conditions. This approach is now widely used by many experimental researchers, especially in the field of plant biology. In this review, we will summarize recent successful examples obtained by using our gene coexpression database, ATTED-II. Specifically, the examples will describe the identification of new genes, such as the subunits of a complex protein, the enzymes in a metabolic pathway and transporters. In addition, we will discuss the discovery of a new intercellular signaling factor and new regulatory relationships between transcription factors and their target genes. In ATTED-II, we provide two basic views of gene coexpression, a gene list view and a gene network view, which can be used as guide gene approach and narrow-down approach, respectively. In addition, we will discuss the coexpression effectiveness for various types of gene sets.

  7. Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

    Science.gov (United States)

    He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

    2018-01-01

    Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 99mTc-TRODAT1- SPECT in Patients with de novo Parkinson's Disease and Differential Diagnosis of Abnormal Movements. Reported Cases

    International Nuclear Information System (INIS)

    Pabon, M.; Orozco, J.; Rojas, J.C.; Takeuchi, Y.; Celis, L.A.; Jimenez, J.; Coral, A.; Vasquez, J.; Badiel, M.; Manzi, E.

    2008-01-01

    Parkinson's disease (PD) is characterized by progressive degeneration of nigrostriatal system with loss of neurons dopamineergicas. TRODAT is an analogue of cocaine which together with the dopamine transporter DAT) is located in the terminal axons of the striatum and reflects the integrity of the dopaminergic system. Objective: To describe the experience with 99mTc-TRODAT1 in patients with differential diagnosis of abnormal movements or EP novo [es

  9. The ELISA-measured increase in cerebrospinal fluid tau that discriminates Alzheimer's disease from other neurodegenerative disorders is not attributable to differential recognition of tau assembly forms.

    Science.gov (United States)

    O'Dowd, Seán T; Ardah, Mustafa T; Johansson, Per; Lomakin, Aleksey; Benedek, George B; Roberts, Kinley A; Cummins, Gemma; El Agnaf, Omar M; Svensson, Johan; Zetterberg, Henrik; Lynch, Timothy; Walsh, Dominic M

    2013-01-01

    Elevated cerebrospinal fluid concentrations of tau discriminate Alzheimer's disease from other neurodegenerative conditions. The reasons for this are unclear. While commercial assay kits are widely used to determine total-tau concentrations, little is known about their ability to detect different aggregation states of tau. We demonstrate that the leading commercial enzyme-linked immunosorbent assay reliably detects aggregated and monomeric tau and evinces good recovery of both species when added into cerebrospinal fluid. Hence, the disparity between total-tau levels encountered in Alzheimer's disease and other neurodegenerative conditions is not due to differential recognition of tau assembly forms or the extent of degeneration.

  10. Differential diagnosis of granulomatous lung disease: clues and pitfalls: Number 4 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

    Science.gov (United States)

    Ohshimo, Shinichiro; Guzman, Josune; Costabel, Ulrich; Bonella, Francesco

    2017-09-30

    Granulomatous lung diseases are a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. Precise clinical evaluation, laboratory testing, pulmonary function testing, radiological imaging including high-resolution computed tomography and often histopathological assessment contribute to make a confident diagnosis of granulomatous lung diseases. Differential diagnosis is challenging, and includes both infectious (mycobacteria and fungi) and noninfectious lung diseases (sarcoidosis, necrotising sarcoid granulomatosis, hypersensitivity pneumonitis, hot tub lung, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, rheumatoid nodules, talc granulomatosis, Langerhans cell histiocytosis and bronchocentric granulomatosis). Bronchoalveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial cryobiopsy, positron emission tomography and genetic evaluation are potential candidates to improve the diagnostic accuracy for granulomatous lung diseases. As granuloma alone is a nonspecific histopathological finding, the multidisciplinary approach is important for a confident diagnosis. Copyright ©ERS 2017.

  11. Two novel antimicrobial defensins from rice identified by gene coexpression network analyses.

    Science.gov (United States)

    Tantong, Supaluk; Pringsulaka, Onanong; Weerawanich, Kamonwan; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Sarnthima, Rakrudee; Roytrakul, Sittiruk; Sirikantaramas, Supaart

    2016-10-01

    Defensins form an antimicrobial peptides (AMP) family, and have been widely studied in various plants because of their considerable inhibitory functions. However, their roles in rice (Oryza sativa L.) have not been characterized, even though rice is one of the most important staple crops that is susceptible to damaging infections. Additionally, a previous study identified 598 rice genes encoding cysteine-rich peptides, suggesting there are several uncharacterized AMPs in rice. We performed in silico gene expression and coexpression network analyses of all genes encoding defensin and defensin-like peptides, and determined that OsDEF7 and OsDEF8 are coexpressed with pathogen-responsive genes. Recombinant OsDEF7 and OsDEF8 could form homodimers. They inhibited the growth of the bacteria Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, and Erwinia carotovora subsp. atroseptica with minimum inhibitory concentration (MIC) ranging from 0.6 to 63μg/mL. However, these OsDEFs are weakly active against the phytopathogenic fungi Helminthosporium oryzae and Fusarium oxysporum f.sp. cubense. This study describes a useful method for identifying potential plant AMPs with biological activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. MPIGeneNet: Parallel Calculation of Gene Co-Expression Networks on Multicore Clusters.

    Science.gov (United States)

    Gonzalez-Dominguez, Jorge; Martin, Maria J

    2017-10-10

    In this work we present MPIGeneNet, a parallel tool that applies Pearson's correlation and Random Matrix Theory to construct gene co-expression networks. It is based on the state-of-the-art sequential tool RMTGeneNet, which provides networks with high robustness and sensitivity at the expenses of relatively long runtimes for large scale input datasets. MPIGeneNet returns the same results as RMTGeneNet but improves the memory management, reduces the I/O cost, and accelerates the two most computationally demanding steps of co-expression network construction by exploiting the compute capabilities of common multicore CPU clusters. Our performance evaluation on two different systems using three typical input datasets shows that MPIGeneNet is significantly faster than RMTGeneNet. As an example, our tool is up to 175.41 times faster on a cluster with eight nodes, each one containing two 12-core Intel Haswell processors. Source code of MPIGeneNet, as well as a reference manual, are available at https://sourceforge.net/projects/mpigenenet/.

  13. Exploring the Diagnostic Potential of Immune Biomarker Co-expression in Gulf War Illness.

    Science.gov (United States)

    Broderick, Gordon; Fletcher, Mary Ann; Gallagher, Michael; Barnes, Zachary; Vernon, Suzanne D; Klimas, Nancy G

    2018-01-01

    Complex disorders like Gulf War illness (GWI) often defy diagnosis on the basis of a single biomarker and may only be distinguishable by considering the co-expression of multiple markers measured in response to a challenge. We demonstrate the practical application of such an approach using an example where blood was collected from 26 GWI, 13 healthy control subjects, and 9 unhealthy controls with chronic fatigue at three points during a graded exercise challenge. A 3-way multivariate projection model based on 12 markers of endocrine and immune function was constructed using a training set of n = 10 GWI and n = 11 healthy controls. These groups were separated almost completely on the basis of two co-expression patterns. In a separate test set these same features allowed for discrimination of new GWI subjects (n = 16) from unhealthy (n = 9) and healthy control subjects with a sensitivity of 70% and a specificity of 90%.

  14. Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

    Science.gov (United States)

    Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

    2011-01-01

    Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

  15. Immunohistochemical Observation of Co-expression of E- and N-cadherins in Rat Organogenesis

    International Nuclear Information System (INIS)

    Sakamoto, Atsushi; Murata, Kazumoto; Suzuki, Hideto; Yatabe, Megumi; Kikuchi, Motoshi

    2008-01-01

    Cadherins are a family of transmembrane glycoproteins that mediate cell-to-cell adhesion. Isoforms, including E- and N-cadherin, have been identified and shown to regulate morphogenesis through homophilic binding. In the ontogeny, the expressions of E- and N-cadherin change spatiotemporally, and the changes in cadherin isoforms, called cadherin switching, impact the mechanical adhesion of cells. Furthermore, cadherin functions as a receptor that transfers information from outside to inside cells, and in terms of switching, it affects cell phenotypes. To observe the expression patterns of E- and N-cadherins during embryogenesis and to identify cells that transiently coexpress both cadherins, we employed a recently developed immunohistochemical double staining technique in rat fetuses. At embryonic day 9, embryonic ectodermal cells more dominantly expressed E-cadherin, while mesodermal cells more dominantly expressed N-cadherin. At embryonic day 10, the expression pattern of E-cadherin in the surface ectoderm and endoderm and that of N-cadherin in the neuroectoderm were established. After embryonic day 10, unique co-expression of E- and N-cadherin was observed in primordia, such as the bulbus cordis, otic pit, notochord, and Rathke’s pouch. In the present study, it was possible to visualize the expression patterns of E- and N-cadherin during early fetal development, which enabled us to morphologically clarify cadherin switching

  16. A contribution to the study of plant development evolution based on gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Francisco J. Romero-Campero

    2013-08-01

    Full Text Available Phototrophic eukaryotes are among the most successful organisms on Earth due to their unparalleled efficiency at capturing light energy and fixing carbon dioxide to produce organic molecules. A conserved and efficient network of light-dependent regulatory modules could be at the bases of this success. This regulatory system conferred early advantages to phototrophic eukaryotes that allowed for specialization, complex developmental processes and modern plant characteristics. We have studied light-dependent gene regulatory modules from algae to plants employing integrative-omics approaches based on gene co-expression networks. Our study reveals some remarkably conserved ways in which eukaryotic phototrophs deal with day length and light signaling. Here we describe how a family of Arabidopsis transcription factors involved in photoperiod response has evolved from a single algal gene according to the innovation, amplification and divergence theory of gene evolution by duplication. These modifications of the gene co-expression networks from the ancient unicellular green algae Chlamydomonas reinhardtii to the modern brassica Arabidopsis thaliana may hint on the evolution and specialization of plants and other organisms.

  17. Exploring Plant Co-Expression and Gene-Gene Interactions with CORNET 3.0.

    Science.gov (United States)

    Van Bel, Michiel; Coppens, Frederik

    2017-01-01

    Selecting and filtering a reference expression and interaction dataset when studying specific pathways and regulatory interactions can be a very time-consuming and error-prone task. In order to reduce the duplicated efforts required to amass such datasets, we have created the CORNET (CORrelation NETworks) platform which allows for easy access to a wide variety of data types: coexpression data, protein-protein interactions, regulatory interactions, and functional annotations. The CORNET platform outputs its results in either text format or through the Cytoscape framework, which is automatically launched by the CORNET website.CORNET 3.0 is the third iteration of the web platform designed for the user exploration of the coexpression space of plant genomes, with a focus on the model species Arabidopsis thaliana. Here we describe the platform: the tools, data, and best practices when using the platform. We indicate how the platform can be used to infer networks from a set of input genes, such as upregulated genes from an expression experiment. By exploring the network, new target and regulator genes can be discovered, allowing for follow-up experiments and more in-depth study. We also indicate how to avoid common pitfalls when evaluating the networks and how to avoid over interpretation of the results.All CORNET versions are available at http://bioinformatics.psb.ugent.be/cornet/ .

  18. Uncovering co-expression gene network modules regulating fruit acidity in diverse apples.

    Science.gov (United States)

    Bai, Yang; Dougherty, Laura; Cheng, Lailiang; Zhong, Gan-Yuan; Xu, Kenong

    2015-08-16

    Acidity is a major contributor to fruit quality. Several organic acids are present in apple fruit, but malic acid is predominant and determines fruit acidity. The trait is largely controlled by the Malic acid (Ma) locus, underpinning which Ma1 that putatively encodes a vacuolar aluminum-activated malate transporter1 (ALMT1)-like protein is a strong candidate gene. We hypothesize that fruit acidity is governed by a gene network in which Ma1 is key member. The goal of this study is to identify the gene network and the potential mechanisms through which the network operates. Guided by Ma1, we analyzed the transcriptomes of mature fruit of contrasting acidity from six apple accessions of genotype Ma_ (MaMa or Mama) and four of mama using RNA-seq and identified 1301 fruit acidity associated genes, among which 18 were most significant acidity genes (MSAGs). Network inferring using weighted gene co-expression network analysis (WGCNA) revealed five co-expression gene network modules of significant (P acidity. Overall, this study provides important insight into the Ma1-mediated gene network controlling acidity in mature apple fruit of diverse genetic background.

  19. Differential distribution of non-structural proteins of foot-and-mouth disease virus in BHK-21 cells

    International Nuclear Information System (INIS)

    Garcia-Briones, Mercedes; Rosas, Maria F.; Gonzalez-Magaldi, Monica; Martin-Acebes, Miguel A.; Sobrino, Francisco; Armas-Portela, Rosario

    2006-01-01

    Differences in the kinetics of expression and cell distribution among FMDV non-structural proteins (NSPs) have been observed in BHK-21-infected cells. 3D pol was the first protein detected by immunofluorescence (1.5 h p.i.), showing a perinuclear distribution. At 2-2.5 h p.i., 2B, 2C, 3B and 3C were detected, mostly exhibiting a punctuated, scattered pattern, while 3A and 3D pol appeared concentrated at one side of the nucleus. This distribution was exhibited by all the NSPs from 3 h p.i., being 2C and, to a lesser extent, precursors 2BC and 3ABBB, the only proteins detected by Western blotting at that infection time. From 4 h p.i., all mature NSPs as well as precursors 2BC, 3ABBB, 3ABB, 3AB and 3CD pol were detected by this technique. In spite of their similar immunofluorescence patterns, 2C and 3A co-localized partially by confocal microscopy at 3.5 h p.i., and 3A, but not 2C, co-localized with the ER marker calreticulin, suggesting differences in the distribution of these proteins and/or their precursors as infection proceeded. Transient expression of 2C and 3AB resulted in punctuated fluorescence patterns similar to those found in early infected cells, while 3A showed a more diffuse distribution. A shift towards a fibrous pattern was noticed for 3ABB, while a major change was observed in cells expressing 3ABBB, which displayed a perinuclear fibrous distribution. Interestingly, when co-expressed with 3D pol , the pattern observed for 3ABBB fluorescence was altered, resembling that exhibited by cells transfected with 3AB. Transient expression of 3D pol showed a homogeneous cell distribution that included, as determined by confocal microscopy, the nucleus. This was confirmed by the detection of 3D pol in nuclear fractions of transfected cells. 3D pol and its precursor 3CD pol were also detected in nuclear fractions of infected cells, suggesting that these proteins can directly interact with the nucleus during FMDV infection

  20. A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.

    Science.gov (United States)

    Umoh, Mfon E; Dammer, Eric B; Dai, Jingting; Duong, Duc M; Lah, James J; Levey, Allan I; Gearing, Marla; Glass, Jonathan D; Seyfried, Nicholas T

    2018-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  1. Using the 2A Protein Coexpression System: Multicistronic 2A Vectors Expressing Gene(s) of Interest and Reporter Proteins.

    Science.gov (United States)

    Luke, Garry A; Ryan, Martin D

    2018-01-01

    To date, a huge range of different proteins-many with cotranslational and posttranslational subcellular localization signals-have been coexpressed together with various reporter proteins in vitro and in vivo using 2A peptides. The pros and cons of 2A co-expression technology are considered below, followed by a simple example of a "how to" protocol to concatenate multiple genes of interest, together with a reporter gene, into a single gene linked via 2As for easy identification or selection of transduced cells.

  2. A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

    Science.gov (United States)

    Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

    2013-01-01

    Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

  3. Emergence of a Stage-Dependent Human Liver Disease Signature with Directed Differentiation of Alpha-1 Antitrypsin-Deficient iPS Cells

    Directory of Open Access Journals (Sweden)

    Andrew A. Wilson

    2015-05-01

    Full Text Available Induced pluripotent stem cells (iPSCs provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ in the gene responsible for alpha-1 antitrypsin (AAT deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells. Expression of 135 genes distinguishes PiZZ iPSC-hepatic cells, providing potential clues to liver disease pathogenesis. The disease-specific cells display intracellular accumulation of mutant AAT prote