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Results for “Genomic profiling”

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At least 1,783 records · Page 99Linked to original sources
PubMed2001

Persistent bacteraemia caused by a single clone of Burkholderia cepacia with unusual phenotype.

We report a case of persistent bacteraemia caused by a single clone of Burkholderia cepacia with unusual characteristics. Six isolates of B. cepacia were recovered from a patient with acute myeloid leukaemia and chemotherapy-induced neutropenia within a 3-week period. All six isolates were initially incompletely identified as B. cepacia with the API 20NE system. The further use of cellular fatty acid analysis and PCR-restriction fragment length polymorphism of the 16S rDNA confirmed the identification. These isolates also displayed an identical but unusual antibiotype. The identical cellular fatty acid profiles and genomic typing generated by random amplified polymorphic DNA identified these isolates as derivatives of a single strain.

Aged↗
PubMed2004

Carbon nutrition of Escherichia coli in the mouse intestine.

Whole-genome expression profiling revealed Escherichia coli MG1655 genes induced by growth on mucus, conditions designed to mimic nutrient availability in the mammalian intestine. Most were nutritional genes corresponding to catabolic pathways for nutrients found in mucus. We knocked out several pathways and tested the relative fitness of the mutants for colonization of the mouse intestine in competition with their wild-type parent. We found that only mutations in sugar pathways affected colonization, not phospholipid and amino acid catabolism, not gluconeogenesis, not the tricarboxylic acid cycle, and not the pentose phosphate pathway. Gluconate appeared to be a major carbon source used by E. coli MG1655 to colonize, having an impact on both the initiation and maintenance stages. N-acetylglucosamine and N-acetylneuraminic acid appeared to be involved in initiation, but not maintenance. Glucuronate, mannose, fucose, and ribose appeared to be involved in maintenance, but not initiation. The in vitro order of preference for these seven sugars paralleled the relative impact of the corresponding metabolic lesions on colonization: gluconate > N-acetylglucosamine > N-acetylneuraminic acid = glucuronate > mannose > fucose > ribose. The results of this systematic analysis of nutrients used by E. coli MG1655 to colonize the mouse intestine are intriguing in light of the nutrient-niche hypothesis, which states that the ecological niches within the intestine are defined by nutrient availability. Because humans are presumably colonized with different commensal strains, differences in nutrient availability may provide an open niche for infecting E. coli pathogens in some individuals and a barrier to infection in others.

Animals↗
PubMed2004

The plant hormone indoleacetic acid induces invasive growth in Saccharomyces cerevisiae.

Fungi must recognize plant-specific signals to initiate subsequent morphogenetic events such as filamentation that lead to infection. Here we show that the plant hormone indoleacetic acid (IAA) induces adhesion and filamentation of Saccharomyces cerevisiae. Genome expression profiling of cells treated with IAA identified Yap1, a fungal specific transcription factor, as a key mediator of this response. Strains lacking YAP1 (yap1-1) are hypersensitive to growth on IAA because they accumulate more IAA than can wild type. Members of a family of transporters the amino acid/auxin:proton symport permeases with homology to AUX1, a putative IAA transporter from plants, are up-regulated in the yap1-1 mutant. Deletion of any one of these transporters makes yap1-1 mutants more resistant to IAA by decreasing its uptake. The permease mutants are defective in IAA perception and filamentation. The ability of a fungus to perceive a plant hormone that causes it to differentiate into an invasive form has important implications for plant-pathogen interactions.

Dose-Response Relationship, Drug↗
PubMed2004

Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation.

Transforming growth factor beta (TGFbeta) is one of few known negative regulators of hematopoiesis, yet the mechanisms by which it affects cell cycle arrest and stem cell quiescence are poorly understood. Induction of the cyclin-dependent kinase inhibitors, p15INK4b (p15) and p21WAF1 (p21) is important for TGFbeta-mediated cytostasis in epithelial cells but not in hematopoietic cells. Using primary human hematopoietic cells and microarray analysis, we identified p57KIP2 (p57) as the only cyclin-dependent kinase inhibitor induced by TGFbeta. Up-regulation of p57 mRNA and protein occurs before TGFbeta-induced G1 cell cycle arrest, requires transcription, and is mediated via a highly conserved region of the proximal p57 promoter. The up-regulation of p57 is essential for TGFbeta-induced cell cycle arrest in these cells, because two different small interfering RNAs that prevent p57 up-regulation block the cytostatic effects of TGFbeta on human hematopoietic cells. Reduction of basal p57 expression by this approach also allows hematopoietic cells to proliferate more readily in the absence of TGFbeta. p57 is a putative tumor suppressor gene whose expression is frequently silenced by promoter hypermethylation in hematologic malignancies. Our studies identify a molecular pathway by which TGFbeta mediates its cytostatic effects on human hematopoietic cells and suggests an explanation for the frequent silencing of p57 expression.

Cell Cycle↗
PubMed2006

A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism.

Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice with Bacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or without M. smithii or the sulfate-reducing bacterium Desulfovibrio piger. Whole-genome transcriptional profiling of B. thetaiotaomicron, combined with mass spectrometry, revealed that, unlike D. piger, M. smithii directs B. thetaiotaomicron to focus on fermentation of dietary fructans to acetate, whereas B. thetaiotaomicron-derived formate is used by M. smithii for methanogenesis. B. thetaiotaomicron-M. smithii cocolonization produces a significant increase in host adiposity compared with monoassociated, or B. thetaiotaomicron-D. piger biassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance.

Animals↗
PubMed2002

Population genomics of drug resistance in Candida albicans.

We followed adaptation in experimental microbial populations to inhibitory concentrations of an antimicrobial drug. The evolution of drug resistance was accompanied in all cases by changes in gene expression that persisted in the absence of the drug; the new patterns of gene expression were constitutive. The changes in gene expression occurred in four replicate populations of the pathogenic fungus Candida albicans during 330 generations of evolution in the presence of the antifungal drug fluconazole. Genome-wide expression profiling of over 5,000 ORFs identified 301 whose expression was significantly modulated. Cluster analysis identified three distinct patterns of gene expression underlying adaptation to the drug. One pattern was unique to one population and included up-regulation of the multidrug ATP-binding cassette transporter gene, CDR2. A second pattern occurred at a late stage of adaptation in three populations; for two of these populations profiled earlier in their evolution, a different pattern was observed at an early stage of adaptation. The succession of early- and late-stage patterns of gene expression, both of which include up-regulation of the multidrug major facilitator transporter gene, MDR1, must represent a common program of adaptation to this antifungal drug. The three patterns of gene expression were also identified in fluconazole-resistant clinical isolates, providing further evidence that these patterns represent common programs of adaptation to fluconazole.

ATP-Binding Cassette Transporters↗
PubMed1999

Mediator protein mutations that selectively abolish activated transcription.

Deletion of any one of three subunits of the yeast Mediator of transcriptional regulation, Med2, Pgd1 (Hrs1), and Sin4, abolished activation by Gal4-VP16 in vitro. By contrast, other Mediator functions, stimulation of basal transcription and of TFIIH kinase activity, were unaffected. A different but overlapping Mediator subunit dependence was found for activation by Gcn4. The genetic requirements for activation in vivo were closely coincident with those in vitro. A whole genome expression profile of a Deltamed2 strain showed diminished transcription of a subset of inducible genes but only minor effects on "basal" transcription. These findings make an important connection between transcriptional activation in vitro and in vivo, and identify Mediator as a "global" transcriptional coactivator.

Cell-Free System↗
PubMed2005

Effect of inhibition of the bc1 complex on gene expression profile in yeast.

Because the respiratory chain is the major site of oxidation of the reduced equivalents and of energy production in aerobic cells, its inhibition has severe impact on the cells. Communication pathways from the respiratory chain are required to allow the cell to sense the defect and respond to it. In this work, we studied changes in gene expression induced by the treatment of yeast cells with myxothiazol, an inhibitor of the bc(1) complex, an enzyme of the respiratory chain. The pattern and time-course expression of the genes resemble those of the environmental stress response, a common gene expression program induced by sudden changes in the environment. In addition, the changes were, for most of the genes, mediated through the transcription factors Msn2/4, which play a central role in the cellular response to these stresses. By using a mutant with a myxothiazol-resistant bc(1) complex, we showed that the changes of expression of the majority of the genes was caused by the inhibition of the bc(1) complex but that other stresses might be involved. The expression pattern of CTT1, coding for a cytoplasmic catalase, was further studied. The expression of this gene was largely dependent on Msn2/4 and the inhibition of the cytochrome bc(1). Addition of oxidants of NADH was found to decrease the expression of CTT1 induced by myxothiazol treatment, suggesting that the accumulation of NADH caused by the inhibition of the respiratory chain may be involved in the signaling pathway from the mitochondria to the transcription factor.

DNA-Binding Proteins↗
PubMed2005

Defining best practice for microarray analyses in nutrigenomic studies.

Microarrays represent a powerful tool for studies of diet-gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues associated with performing nutritional microarray studies, often means that compromises have to be made in the number and type of samples analysed. Additionally, technical variations between array platforms and analytical procedures will almost inevitably lead to differences in the transcriptional responses observed. Consequently, conflicting data may be produced, important effects may be missed and/or false leads generated (e.g. apparent patterns of differential gene regulation that ultimately prove to be incorrect or not significant). This is likely to be particularly true in the field of nutrition, in which we expect that many dietary bioactive agents at nutritionally relevant concentrations will elicit subtle changes in gene transcription that may be critically important in biological terms but will be difficult to detect reliably. Thus, great care should always be taken in designing and executing microarray studies. This article seeks to provide an overview of both the main practical and theoretical considerations in microarray use that represent potential sources of technical variation and error. Wherever possible, recommendations are made on what we propose to be the best approach. The overall aims are to provide a basic framework of advice for researchers who are new to the use of microarrays and to promote a discussion of standardisation and best practice in the field.

Animals↗
PubMed2004

Evolutionary relationships within 'pygmaeus' group microphallids using genetic analysis and scanning electron microscopy.

There are four species of 'pygmaeus' microphallids, namely Microphallus pygmaeus, M. piriformes, M. pseudopygmaeus and M. triangulatus (Trematoda: Microphallidae) which are parasites of marine birds and their sporocysts give rise to transmissible metacercariae inside littoral gastropods (mostly littorines). Universally primed polymerase chain reaction (UP-PCR) showed no apparent pattern between genetic diversity of the metacercariae as estimated by genomic banding profiles and their geographic region or molluscan host species. At the same time UP-PCR product cross-hybridization showed that M. pseudopygmaeus and M. triangulatus are genetically very similar, indicating that these taxa represent one species complex. In contrast, M. pygmaeus and M. piriformes are genetically well separated from each other and also from the pseudopygmaeus-triangulatus complex. Scanning electron microscopy of ventral spines, and analyses of spine angles and the number of teeth per spine, showed that all species differed significantly from one another. It was concluded that M. piriformes represents the original western member of the 'pygmaeus' group. Microphallus pygmaeus probably diverged from M. piriformes as it progressively specialized for sea duck final hosts. Microphallus pseudopygmaeus and M. triangulatus diverged from each other and the piriformes-pygmaeus ancestral line relatively recently. Microphallus pseudopygmaeus specialized for adoption of a wide range of gastropod host species and M. triangulatus developed morpho-functional specialization associated with final host exploitation.

Animals↗
PubMedDate not supplied

Toxicogenomics in drug development.

Toxicogenomics represents the merging of toxicology with technologies that have been developed, together with bioinformatics, to identify and quantify global gene expression changes. It represents a new paradigm in drug development and risk assessment, which promises to generate a wealth of information towards an increased understanding of the molecular mechanisms that lead to drug toxicity and efficacy, and of DNA polymorphisms responsible for individual susceptibility to toxicity. Gene expression profiling, through the use of DNA microarray and proteomic technologies will aid in establishing links between expression profiles, mode of action and traditional toxic endpoints. Such patterns of gene expression, or 'molecular fingerprints' could be used as diagnostic or predictive markers of exposure, that is characteristic of a specific mechanism of induction of that toxic or efficacious effect. It is anticipated that toxicogenomics will be increasingly integrated into all phases of the drug development process particularly in mechanistic and predictive toxicology, and biomarker discovery. This review provides an overview of the expression profiling technologies applied in toxicogenomics. and discusses the promises as well as the future challenges of applying this discipline to the drug development process.

Animals↗
PubMed2006

Pharmacogenomics and antidepressant drugs.

While antidepressant pharmacotherapy is an effective treatment of depression, it still is hampered by a delayed time of onset of clinical improvement and a series of side effects. Moreover, a substantial group of patients has only limited response or fails to respond at all. One source accounting for these variations are genetic differences as currently analysed by single nucleotide polymorphisms (SNP) mapping. In recent years a number of pharmacogenetic studies on antidepressant drugs have been published. So far they mostly focused on metabolizing enzymes of the cytochrome P450 (CYP) families and genes within the monoaminergic system with compelling evidence for an effect of CYP2D6 polymorphisms on antidepressant drug plasma levels and of a serotonin transporter promoter polymorphism on clinical response to a specific class of antidepressants, the selective serotonin reuptake inhibitors. It is clear, however, that other candidate systems have to be considered in the pharmacogenetics of antidepressant drugs, such as neuropeptidergic systems, the hypothalamus-pituitary adrenal (HPA) axis and neurotrophic systems. There is recent evidence that polymorphisms in genes regulating the HPA axis have an important impact on response to antidepressants. These studies mark the beginning of an emerging standard SNP profiling system that ultimately allows identifying the right drug for the right patient at the right time.

Antidepressive Agents↗
PubMed2026

Salivary duct carcinoma- contemporary nuts and bolts from pathologist perspective.

INTRODUCTION: Salivary gland carcinomas are highly heterogeneous malignancies that present a complex variety of histological features and distinct clinical behaviors, with salivary duct carcinoma (SDCa) as the most clinically severe and aggressive subtype. The standard of care for these patients is a combined approach of surgery followed by radiotherapy. The aggressive clinical course of SDCa is primarily driven by frequent disease recurrences and systemic spread. AREAS COVERED: The publication of WHO 5th Classification of Head and Neck tumors has sparked a surge in research targeting SDCa. Owing to the highly aggressive behavior of the tumor, most literature heavily emphasizes the molecular pathology of SDCa.A systematic literature search was conducted using the PubMed with the following search terms: salivary duct carcinoma AND pathology OR updates OR molecular OR signaling pathway OR gene expression OR mutation OR oncogene OR tumor suppressor OR DNA methylation OR tumor microenvironment. Results were limited to primary research articles in English language. EXPERT OPINION: This article outlines key advancements in SDCa morphology, molecular pathology, and targeted therapies. Patient management in precision oncology will be fundamentally transformed by the classification of new morphologic subtypes, the discovery of molecular biomarkers, and an enhanced comprehension of tumor microenvironment.

HER 2↗
PubMed2025

MicroRNAs signatures in small extracellular vesicles for psychological resilience in young adults using machine learning.

AIMS: Psychological resilience refers to an individual's capacity to adapt to adverse events. MicroRNAs (miRNAs) play a crucial role in regulating post-transcriptional processes, while small extracellular vesicles (sEVs) act as transport vehicles. This study aimed to employ genome-wide profiling to identify and validate differences in the expression of resilience-associated sEV-miRNAs between low resilience (LR) and high resilience (HR) in young adults. METHODS: Eighty participants were divided into LR or HR based on the Connor - Davidson Resilience Scale (CD-RISC). The expression levels of the target sEV-miRNAs in LR and HR were compared and analyzed. RESULTS: Expression analyses demonstrated significant differences in let-7b, miR-151b, miR-335, and miR-193a between LR and HR (p&#x2009;<&#x2009;0.01), with let-7b showing the highest discriminative ability. The AUC values for each sEV-miRNA ranged from 0.74 to 0.94, based on logistic regression and three machine learning models: random forest, support vector machine, and eXtreme gradient boosting. Based on leave-one-out cross-validation in different models, the combined four sEV-miRNAs demonstrated strong performance for detecting LR (AUC&#x2009;=&#x2009;0.87-0.90). Sex-specific differences were also observed, with female participants showing more pronounced resilience signatures in targeted sEV-miRNAs. CONCLUSIONS: These findings suggest that sEV-miRNAs hold potential as biomarkers for psychological resilience in young adults.

Humans↗
PubMed2001

Nasal MRSA colonization of AIDS Patients cared for in a Brazilian university hospital.

Weekly culture surveillance was conducted over a 2-year period to determine the incidence of methicillin-resistant Staphylococcus aureus nasal colonization among acquired immunodeficiency syndrome patients cared for in a day-care unit and in an infectious diseases unit. Analysis of genomic DNA profiles showed a predominant pattern in both units.

Acquired Immunodeficiency Syndrome↗