SEARCH · PubMed Health

Results for “Biological sequence analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources

PubMed2005

Thrombospondin 1 as possible key factor in the hemocompatibility of endocoronary prostheses.

Intracoronary stenting has markedly improved the patency of native coronary arteries after percutaneous transluminal coronary angioplasty (PTCA). Advances in stent technology and design, including drug releasing stents, have contributed to reduce the long-term restenosis rate. However, stenosis caused by neointimal hyperplasia, vascular remodeling and thrombosis is still a major problem after endocoronary stent procedures. This study focuses on differential gene expression of circulating peripheral blood cells after 90 min exposure to stents to search for initially activated cellular pathways, which may foster restenosis. Fresh human whole blood (1 IU heparin/ml), taken from non-medicated healthy volunteers, was incubated under flow conditions in an in vitro closed-loop stent-testing model (modified Chandler-Loop). Differential gene expression compared to resting conditions and to the experimental controls was investigated by a DNA-microarray technique encoding for over 17,000 genes simultaneously. As expected, a large variety of genes showed differential gene expression. Interestingly, Thrombospondin 1 (TSP-1), which plays a key role in initial immune defense, was found to be the most markedly up-regulated gene. We propose TSP-1 expression as an early indicator for the activation of immune responses following intracoronary stenting. After clarifying the participation of TSP-1 in vivo, future studies will therefore focus on TSP-1 as a potential prognostic factor, which may also help to develop and control new surface materials with an improved biocompatibility.

Adult↗

PubMed2006

Accurate prediction of enzyme subfamily class using an adaptive fuzzy k-nearest neighbor method.

Amphiphilic pseudo-amino acid composition (Am-Pse-AAC) with extra sequence-order information is a useful feature for representing enzymes. This study first utilizes the k-nearest neighbor (k-NN) rule to analyze the distribution of enzymes in the Am-Pse-AAC feature space. This analysis indicates the distributions of multiple classes of enzymes are highly overlapped. To cope with the overlap problem, this study proposes an efficient non-parametric classifier for predicting enzyme subfamily class using an adaptive fuzzy r-nearest neighbor (AFK-NN) method, where k and a fuzzy strength parameter m are adaptively specified. The fuzzy membership values of a query sample Q are dynamically determined according to the position of Q and its weighted distances to the k nearest neighbors. Using the same enzymes of the oxidoreductases family for comparisons, the prediction accuracy of AFK-NN is 76.6%, which is better than those of Support Vector Machine (73.6%), the decision tree method C5.0 (75.4%) and the existing covariant-discriminate algorithm (70.6%) using a jackknife test. To evaluate the generalization ability of AFK-NN, the datasets for all six families of entirely sequenced enzymes are established from the newly updated SWISS-PROT and ENZYME database. The accuracy of AFK-NN on the new large-scale dataset of oxidoreductases family is 83.3%, and the mean accuracy of the six families is 92.1%.

Algorithms↗

PubMed2006

Alternative splicing: new insights from global analyses.

Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation of proteomic and functional diversity in metazoan organisms. Efforts are now being directed at establishing the full repertoire of functionally relevant transcript variants generated by alternative splicing, the specific roles of such variants in normal and disease physiology, and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions. Recent progress in these areas is summarized in this review.

Alternative Splicing↗

PubMed2004

Recent advances in bladder cancer diagnostics.

Transitional cell carcinoma of the bladder is a significant cause of morbidity and mortality worldwide. The diagnosis of bladder cancer is based on the information provided by cystoscopy, the gold standard, in combination with urinary cytology findings. Many tumor markers have been evaluated for detecting and monitoring of the disease in serum, bladder washes, and urinary specimens. However, none of these biomarkers reported to date has shown sufficient sensitivity and specificity for the detection of the whole spectrum of bladder cancer diseases in routine clinical practice. The advent of high-throughput microarrays is accelerating the identification process of the molecular events characteristic of bladder tumors' phenotype and subsequent clinical behavior. The information provided by these analyses is resulting not only in the identification of novel therapeutic targets for bladder cancer, but also in the development of diagnostic tools. This review summarizes the reports utilizing high-throughput microarrays in bladder cancer and the implications of these analyses in the diagnosis and clinical management of patients with bladder cancer.

Biomarkers, Tumor↗

PubMed2004

Tabu search algorithm for DNA sequencing by hybridization with isothermic libraries.

In this paper, a problem of isothermic DNA sequencing by hybridization (SBH) is considered. In isothermic SBH a new type of oligonucleotide libraries is used. The library consists of oligonucleotides of different lengths depending on an oligonucleotide content. It is assumed that every oligonucleotide in such a library has an equal melting temperature. Each nucleotide adds its increment to the oligonucleotide temperature and it is assumed that A and T add 2 degrees C and C and G add 4 degrees C. The hybridization experiment using isothermic libraries should provide data with a lower number of errors due to an expected similarity of melting temperatures. From the computational point of view the problem of isothermic DNA sequencing with errors is hard, similarly like its classical counterpart. Hence, there is a need for developing heuristic algorithms that construct good suboptimal solutions. The aim of the paper is to propose a heuristic algorithm based on tabu search approach. The algorithm solves the problem with both positive and negative errors. Results of an extensive computational experiment are presented, which prove the high quality of the proposed method.

Algorithms↗

PubMed2004

A double segment periodicity underlies segment generation in centipede development.

The number of leg-bearing segments in centipedes varies extensively, between 15 and 191, and yet it is always odd. This suggests that segment generation in centipedes involves a stage with double segment periodicity and that evolutionary variation in segment number reflects the generation of these double segmental units. However, previous studies have revealed no trace of this. Here we report the expression of two genes, an odd-skipped related gene (odr1) and a caudal homolog, that serve as markers for early steps of segment formation in the geophilomorph centipede, Strigamia maritima. Dynamic expression of odr1 around the proctodaeum resolves into a series of concentric rings, revealing a pattern of double segment periodicity in overtly unsegmented tissue. Initially, the expression of the caudal homolog mirrors this double segment periodicity, but shortly before engrailed expression and overt segmentation, the intercalation of additional stripes generates a repeat with single segment periodicity. Our results provide the first clues about the causality of the unique and fascinating "all-odd" pattern of variation in centipede segment numbers and have implications for the evolution of the mechanisms of arthropod segmentation.

Animals↗

PubMed2005

Gene expression profiling in streptozotocin treated mouse liver using DNA microarray.

Streptozotocin (SZ) is known to exert toxic effects not only on pancreatic islet beta cells but also on other organs including liver. For analyzing changes in genes expression associated with SZ toxicity, we performed DNA microarray analyses on the liver obtained from SZ-treated mice. Eight-week-old male ICR mice were treated i.p. with 200 mg/kg of SZ, and the blood and liver were taken at 6, 24 and 48 h after the treatment. Labeled cRNA prepared from total RNA of the liver was hybridized to the GeneChip Murine Genome U74A V.2 (Affymetrix). The number of the probe sets, which were clearly up-regulated or down-regulated, were over 100 at 6 and 24h after the SZ-treatment, and it decreased at 48 h after the treatment. Many of the up-regulated genes were categorized into cell cycle/apoptosis related genes, immune/allergy related genes and stress response/xenobiotic metabolism related genes. On the other hand, genes related to glucose, lipid and protein metabolisms were down-regulated. These changes started prior to the elevation of the serum glucose levels, indicating the direct action of SZ on the liver rather than the secondary effect of diabetes. This may be related with the previously reported hepatic changes such as lipid peroxidation, mitochondrial swelling and inhibition of hepatocyte proliferation observed before the development of hyperglycemia.

Animals↗

PubMed2005

Isolation, characterization and expression of a novel vegetative insecticidal protein gene of Bacillus thuringiensis.

Twenty-four serovars of Bacillus thuringiensis (Bt) were screened by polymerase chain reaction to detect the presence of vegetative insecticidal protein gene (vip)-like sequences by using vip3Aa1-specific primers. vip-like gene sequences were identified in eight serovars. These genes were cloned and sequenced. The deduced amino acid sequence of the vip3Aa14 gene from Bacillus thuringiensis tolworthi showed considerable differences as compared to those of Vips reported so far. The vip3Aa14 gene from Bt tolwarthi was expressed in Escherichia coli using expression vector pET29a. The expressed Vip3Aa14 protein was found in cytosolic supernatant as well as pellet fraction, but the protein was more abundant in the cytosolic supernatant fraction. Both full-length and truncated (devoid of signal sequence) Vips were highly toxic to the larvae of Spodoptera litura and Plutella xylostella. Truncation of Vip3Aa14 protein at N-terminus did not affect its insecticidal activity.

Animals↗

PubMed2006

Depot-specific prostaglandin synthesis in human adipose tissue: a novel possible mechanism of adipogenesis.

Despite the magnitude of the obesity epidemic, the mechanisms that contribute to increases in fat mass and to differences in fat depots are still poorly understood. Prostanoids have been proposed as potent adipogenic hormones, e.g. metabolites of prostaglandin J2 (PGJ2) bind and activate PPARgamma. We hypothesize that an altered expression of enzymes in PGJ2 synthesis may represent a novel pathogenic mechanism in human obesity. We characterized adipose depot-specific expression of enzymes in PGJ2 synthesis, prostaglandin transporter and PPARgamma isoforms. Paired omental and subcutaneous adipose tissue samples were obtained from 26 women undergoing elective abdominal surgery and gene expression examined in whole tissue and cultured preadipocytes using an Affymetrix cDNA microarray technique and validated with quantitative real-time PCR. All enzymes involved in prostaglandin synthesis were expressed in both adipose tissues. Expression of prostaglandin synthase-1 (PGHS1), prostaglandin D synthase (PTGDS), human prostaglandin transporter (hPGT) and PPARgamma2 was higher in OM adipose tissue compared to SC, whereas 17beta-hydroxysteroid dehydrogenase 5 (AKR1C3) showed predominance in SC adipose tissue. In SC adipose tissue, PGHS1 mRNA expression increased with BMI. The differential, depot-specific expression of key enzymes involved in transport, synthesis and metabolism of prostaglandins may have an important impact upon fat cell biology and may help to explain some of the observed depot-specific differences. In addition, the positive correlation between PGHS1 and BMI offers the novel hypothesis that the regulation of PG synthesis may have a role in determining fat distribution in human obesity.

3-Hydroxysteroid Dehydrogenases↗

PubMed2004

Gene expression profiling of Escherichia coli expressing double Vitreoscilla haemoglobin.

In a recent investigation, expression of a double Vitreoscilla haemoglobin (two fused VHb molecules) in Escherichia coli grown in shake flasks resulted in higher final cell density and considerably higher levels of ribosomes and tRNA. In this study, we have investigated the E. coli transcriptome in cells expressing native VHb, double VHb and control cells lacking VHb by hybridising mRNA from the different constructs to high-density oligonucleotide arrays. Within the 95% confidence interval, 4 and 5% of all detected genes in native VHb cells were up- and down-regulated, respectively; in double VHb cells the corresponding numbers were 6 and 10%, respectively. Dividing the data into different functional groups revealed that genes involved in energy metabolism, central intermediary metabolism and cell processes were the most affected at the mRNA level. Particularly, the up-regulation of genes involved in translation and posttranslational modification observed in double VHb cells demonstrates a strong relationship between the regulation of ribosomal genes and the actual number of ribosomes.

Bacterial Proteins↗

PubMed2005

Restraint stress alters lung gene expression in an experimental influenza A viral infection.

In the present study the global effect of restraint stress on gene expression in the murine lung during an experimental influenza A/PR8 viral infection was examined. Gene expression profiling using high density oligonucleotide microarrays revealed that the expression of 95 genes was altered on day 3 post infection (p.i.), while 48 genes were altered on day 7 p.i. Restraint stress reduced and delayed the expression of specific cytokines, cell adhesion molecules and cell surface receptors indicating alterations in cell migration to the site of infection. Furthermore, mapping of the candidate genes to known pathways revealed that genes associated with host defense and immune responses, including chemotaxis and chemokine function, antigen presentation and processing, MHC class II receptor function and inflammation were the major pathways affected by restraint stress.

Animals↗

PubMed2005

Genomic profiling of restraint stress-induced alterations in mouse T lymphocytes.

DNA damage-, DNA repair-, and apoptosis-related gene expression in CD3(+) T lymphocytes of BALB/c mice subjected to 2-h restraint stress were compared to that in CD3(+)T lymphocytes from control mice. Using targeted cDNA arrays, significant increases in expression of genes serving as sensors of DNA damage, including MSH genes and RAD53, were observed. GADD45g, a gene responsible for regulating cell cycle arrest and apoptosis, was significantly induced; as was Pura, a gene involved in cell proliferation. These data suggest that, at the molecular level, stress activates genes responsible for priming the T cell to either undergo apoptosis or proliferation.

Animals↗

PubMed2006

Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).

We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p<0.01 for all tissues). As early as 24h after single injection of the two steroids, 878, 2681 and 14 probe sets were commonly stimulated or inhibited (p<0.01, change> or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.

Anabolic Agents↗

PubMed2005

SLLE for predicting membrane protein types.

Introduction of the concept of pseudo amino acid composition (PROTEINS: Structure, Function, and Genetics 43 (2001) 246; Erratum: ibid. 44 (2001) 60) has made it possible to incorporate a considerable amount of sequence-order effects by representing a protein sample in terms of a set of discrete numbers, and hence can significantly enhance the prediction quality of membrane protein type. As a continuous effort along such a line, the Supervised Locally Linear Embedding (SLLE) technique for nonlinear dimensionality reduction is introduced (Science 22 (2000) 2323). The advantage of using SLLE is that it can reduce the operational space by extracting the essential features from the high-dimensional pseudo amino acid composition space, and that the cluster-tolerant capacity can be increased accordingly. As a consequence by combining these two approaches, high success rates have been observed during the tests of self-consistency, jackknife and independent data set, respectively, by using the simplest nearest neighbour classifier. The current approach represents a new strategy to deal with the problems of protein attribute prediction, and hence may become a useful vehicle in the area of bioinformatics and proteomics.

Algorithms↗

PubMed2005

A simple and economic preservation method for genomic bacterial DNA from clinically significant pathogens.

Bacterial culture was allowed to dry to completeness on Columbia agar base with defibrinated horse blood. Following 6 months storage at room temperature, microbial DNA was extracted and successfully amplified by PCR. This storage technique has the advantage over other methods of not requiring (i) a DNA extraction protocol prior to storage and (ii) refrigeration and/or freezing. This technique maybe useful in the transportation of bacterial genomic DNA in nonviable cells as well as reliable method for the storage of DNA in underdeveloped countries.

Base Sequence↗

PubMedDate not supplied

Cocaine-induced changes in the expression of apoptosis-related genes in the fetal mouse cerebral wall.

It has been demonstrated that exposure to cocaine increases cell death in the fetal CNS. To examine the molecular mechanisms of this effect, we employed mouse oligo microarrays followed by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) to compare expressions of apoptosis-related genes in the cerebral wall of 18-day-old (E18) fetuses from cocaine-treated (20 mg/kg cocaine, s.c., b.i.d., E8th-E18th) and drug-naive (saline, s.c.) mice. Out of approximately 400 relevant genes in the arrays, 53 showed alterations in expression in cocaine-exposed fetuses. Upregulation was observed in 35 proapoptotic and 8 antiapoptotic genes; 4 proapoptotic and 6 antiapoptotic genes were down-regulated. The affected genes encode a wide range of apoptosis-related proteins, including death receptors (NTF-R1, NTF-R2, DR3, DR5, LTbeta-R, GITR, P57 TR-1) and their adaptor and regulatory proteins (MASGE-D1, TRAF-2, SIVA, MET, FLIP, FAIM, IAP1, ATFA), members of transcription regulatory pathways (JNK, NF-kappaB, P53), members of BCL-2 family of proteins (BID, BAD, BAX, BIK, NIP21, NIP3, NIX, BCL-2), DNA damage sensor (PARP-1), caspases and their substrates and regulatory proteins (caspases 8, 4, 9, and 3, ACINUS, CIDE-A, CIDE-B, GAS2), mitochondrially released factors (cytochrome c, AIF, PRG3), specific endoplasmic reticulum- and oxidative stress-associated factors (BACH2, ABL1, ALG2, CHOP), members of cell survival AKT and HSP70 pathways (PIK3GA, PTEN, HSP70, BAG1, BAG2), and others. This suggests that cocaine affects survival of developing cerebral cells via multiple apoptosis-regulating mechanisms.

Animals↗

PubMedDate not supplied

Gene expression changes related to growth and differentiation in the fetal and juvenile reproductive system of the female rat: evaluation of microarray results.

Microarrays make it possible to evaluate the responses of a major fraction of the genome in response to physiological perturbation or exogenous insult. This represents a huge advance in our ability to detect changes in gene expression that may be responsible for physiological or toxicological responses. Our laboratory is interested in the effects of estrogens on female reproductive system development and function. We have evaluated the changes in gene expression in response to estrogens in the female reproductive tract of rats during embryo/fetal development and in the juvenile rat (which is capable of mounting a uterotrophic response). The results of these experiments indicate that a number of genes (dozens to hundreds) are changed in a reproducible, dose-related manner in response to estrogens. These results have been published elsewhere; the purpose of this review is to evaluate, based on information from the literature, the potential role of selected genes on processes of cell proliferation and differentiation, and to suggest plausible relationships among these genes in eliciting responses at the tissue or organ level. We also discuss the utility of gene-expression experiments in elucidating the shape of the dose-response curve at low doses. In particular, we show that the dose-response for gene expression in the juvenile rat uterus is monotonic down to levels a few orders of magnitude below the NOEL for a uterotrophic response, suggesting that gene expression (and by inference higher order responses) do not follow patterns that are unpredictable based on response at higher dosages.

Animals↗

PubMed2003

Steroidogenesis and apoptosis in the mammalian ovary.

Ovarian cell death is an essential process for the homeostasis of ovarian function in human and other mammalian species. It ensures the selection of the dominant follicle and the demise of excess follicles. In turn, this process minimizes the possibility of multiple embryo development during pregnancy and assures the development of few, but healthy embryos. Degeneration of the old corpora lutea in each estrous/menstrual cycle by programmed cell death is essential to maintain the normal cyclicity of ovarian steroidogenesis. Although there are multiple pathways that can determine cell death or survival, crosstalk among endocrine, paracrine and autocrine factors, as well as among protooncogenes, tumor suppressor genes, survival genes and death genes, plays an important role in determining the fate of ovarian somatic and germ cells. The establishment of immortalized rat and human steroidogenic granulosa cell lines and the investigation of pure populations of primary granulosa cells allows systematic studies of the mechanisms that control steroidogenesis and apoptosis in granulosa cells. We have discovered that during initial stages of granulosa cell apoptosis progesterone production does not decrease. In contrast, we found that it is elevated up to 24h following the onset of the apoptotic stimuli exerted by starvation, cAMP, p53 or TNF-alpha stimulation, before total cell collapse. These observations raise the possibility for an alternative unique apoptotic pathway, one not involving mitochondrial Cyt C release associated with the destruction of mitochondrial structure and steroidogenic function. Using mRNA from apoptotic cells and affymetrix DNA microarray technology we discovered that granzyme B, a protease that normally resides in T cytotoxic lymphocytes and natural killer cells of the immune system is expressed and activated in granulosa cells. Thus, the apoptotic signals could bypass mitochondrial signals for apoptosis, which can preserve their steroidogenic activity until complete cell destruction. This unique apoptotic pathway assures cyclicity of estradiol and progesterone release in the estrous/menstruous cycle even during the initial stages of apoptosis.

Animals↗