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PubMedDate not supplied

[Glucocorticoids at the threshold of the new millennium: recent findings on the anti-inflammatory and immunomodulator mechanisms of action and future perspectives].

The aim of this work was to provide an updated review of the mechanisms of action of glucocorticoids. We carried out a MEDLINE search (1970 to present) using "glucocorticoids" as the keyword, both on its own (subheadings: "genetics, immunology, metabolism, physiology, therapeutic use") and combined with "inflammation", "glucocorticoid response element", "gene expression regulation", "NF-kappa B", "transcription factor AP-1", "receptors, glucocorticoid", "chemokines", "cytokines", "cytokine receptors", "resistance", "sensitivity", "annexin-I", "apoptosis", "repressors" and "activators", respectively. Original, partially unpublished data from our research group was also reported. Although we reviewed the sources available, we did not adopt any statistic procedures for data extraction, as the review deals only with basic research. The results of this review indicate that glucocorticoids act through different mechanisms: they can regulate the transcription of a number of genes (genomic mechanisms), interfere with cell activation factors (mechanisms of repression of cell activation factors), and inhibit cell activation via a direct interaction with the cell membrane and/or some of its components (non-genomic mechanisms). There is some evidence that most of the anti-inflammatory effects of glucocorticoids are mediated by repression of transcriptor factors, whereas their metabolic effects appear to be predominantly mediated by genomic mechanisms. This observation has prompted the search for new steroid compounds endowed with more selective anti-inflammatory properties than those currently available. We conclude that better understanding of the mechanisms of action of steroids may result in the development of new molecules with a better risk/benefit ratio.

Adjuvants, Immunologic↗

PubMed2003

[An introduction of several programs used in genomic analysis].

Genomics is a novel subject that has been developed accompanying with the progress of human genome project. Genomics deals with the chemistry component, structure organization and evolution of genome at global level. As genomics associated with huge data, bioinformatics plays an important role in these processes of data production, data management and data mining. At present, many reliable programs have been used in genomic research successfully, which are usually accessible and downloaded freely. We address here the principles of some programs used wildly in genomics such as sequence alignment, sequence assembly, repeat identification and gene prediction, which are exemplified with typical programs respectively.

English Abstract↗

PubMed1991

Low-level inversion of the L component of pseudorabies virus is not dependent on sequence homology.

Pseudorabies virus has a class 2 genome in which the S component is found in two orientations relative to the L component. The L component is bracketed by sequences that are partially homologous; it is found mainly in one orientation, but a small proportion is inverted (J. M. DeMarchi, Z. Lu, G. Rall, S. Kuperschmidt, and T. Ben-Porat, J. Virol. 64:4968-4977, 1990). We have ascertained the role of the patchy homologous sequences bracketing the L component in its inversion. A viral mutant, vYa, from which the sequences at the right end of the L component were deleted was constructed. Despite the absence of homologous sequences bracketing the L component in vYa, its L component inverted to an extent similar to that of the L component in the wild-type virus. These results show the following. (i) The low-frequency inversion of the L component of PrV is not mediated by homologous sequences bracketing this component. (ii) Cleavage of concatemeric DNA at the internal junction between the S and L components is responsible for the appearance of the minority of genomes with an inverted L component in populations of pseudorabies virus. (iii) The signals present near or at the end of the S component are sufficient to allow low-frequency cleavage of concatemeric DNA; the sequences at the end of the L component are not essential for cleavage, although they enhance it considerably.

Animals↗

PubMed2001

Representational difference analysis reveals genomic differences between Q. robur and Q. suber: implications for the study of genome evolution in the genus Quercus.

Very similar genome sizes, similar karyotypes and heterochromatin organisation, and identical number/position of ribosomal loci characterise the common oak (Q. robur) and the cork oak (Q. suber), two distantly related oak species. Representational Difference Analysis (RDA) was used to subtract the genome of Q. suber from the genome of Q. robur in order to search for genome differentiation. A library of 400 clones (bearing RDA fragments) representing genome differences between the two species was obtained. Seven Q. robur-specific DNA sequences were analysed with respect to their molecular and chromosome organisation. All belong to the dispersed repetitive component of the genome, as revealed by Southern hybridisation and in situ hybridisation. They are present in the Q. robur genome in between 100 and 700 copies, and are distributed along the length of almost all chromosomes. A search for homologies between RDA fragments and sequences in Genbank revealed similarities of all RDA fragments with known retrotransposons. The RDA fragments were also tested for their presence/absence in the genomes of six additional oak species belonging to different phylogenetic groups, in order to examine the evolutionary dynamics of these DNA sequences.

Base Sequence↗

PubMed2002

Electrophoretic identification of new genomic profiles with a modified selective amplification of microsatellite polymorphic loci technique based on AT/AAT polymorphic repeats.

The present paper introduces improvements of the conventional selective amplification of microsatellite polymorphic loci (SAMPL) technique, that exploit AT-rich microsatellite primers. Generally, AT/AAT microsatellites are frequent components of eukaryotic genomes, but their ubiquity and polymorphic information content (PIC) could not be exploited yet, because standard SAMPL conditions did not allow amplifications. Here we report (i) on the design of new versatile AT-rich microsatellite primers, that are combined with (ii) a modified SAMPL adapter primer (called EcoRI-Short), and (iii) special polymerase chain reaction (PCR) amplification regimes. The novel SAMPL procedure expands the range of useful microsatellite primers to AT-rich sequences and produces a high number of bands and a clear banding pattern, and detects polymorphisms in otherwise nonpolymorphic genomes of plants (Dioscorea alata, D. rotundata) and a fungus (Mycosphaerella fijiensis).

AT Rich Sequence↗

PubMed2007

Recent proliferation and translocation of pollen group 1 allergen genes in the maize genome.

The dominant allergenic components of grass pollen are known by immunologists as group 1 allergens. These constitute a set of closely related proteins from the beta-expansin family and have been shown to have cell wall-loosening activity. Group 1 allergens may facilitate the penetration of pollen tubes through the grass stigma and style. In maize (Zea mays), group 1 allergens are divided into two classes, A and B. We have identified 15 genes encoding group 1 allergens in maize, 11 genes in class A and four genes in class B, as well as seven pseudogenes. The genes in class A can be divided by sequence relatedness into two complexes, whereas the genes in class B constitute a single complex. Most of the genes identified are represented in pollen-specific expressed sequence tag libraries and are under purifying selection, despite the presence of multiple copies that are nearly identical. Group 1 allergen genes are clustered in at least six different genomic locations. The single class B location and one of the class A locations show synteny with the rice (Oryza sativa) regions where orthologous genes are found. Both classes are expressed at high levels in mature pollen but at low levels in immature flowers. The set of genes encoding maize group 1 allergens is more complex than originally anticipated. If this situation is common in grasses, it may account for the large number of protein variants, or group 1 isoallergens, identified previously in turf grass pollen by immunologists.

Antigens, Plant↗

PubMed2005

Construction and characterization of Listeria monocytogenes mutants with in-frame deletions in the response regulator genes identified in the genome sequence.

Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.

Animals↗

PubMed2000

Host range and symptom variation of pseudorecombinant virus produced by two distinct bipartite geminiviruses.

Within the whitefly group only the species Bemisia tabaci (Gennadius) is the vector. Most whitefly-transmitted geminiviruses possess bipartite DNA genomes, DNAs A and B. Although they are closely related to each other, the production of viable pseudorecombinants between bipartite geminiviruses by reassortment of infectious cloned components is generally limited to strains of a particular virus. Following exchange of cloned genomic components of Sida golden mosaic virus (SiGMV/Hoyv) and Abutilon mosaic virus (AbMV), the pseudorecombinant viruses were infectious in various host plants. The symptom type of pseudorecombinant virus was in most cases determined by DNA B. However, in some host plants also DNA A of the pseudorecombinant virus was involved in the symptom phenotype.

Base Sequence↗

PubMed1999

Assessing linkage of monoamine oxidase B in a genome-wide scan using a univariate variance components approach.

We report results when one alcoholism related quantitative trait, monoamine oxidase B (MAOB), is analyzed by the variance components approach for linkage [Amos, 1994; Amos et al., 1996] using the Collaborative Study on the Genetics of Alcoholism data set provided for the Genetic Analysis Workshop 11. We used two different covariate models, one with age at interview, sex, ethnicity, and smoking status and the other with age at interview, sex, and ethnicity. The univariate analysis showed 24 markers on four different chromosomes (1, 4, 9, and 12) to have evidence for linkage with the quantitative trait (single-point and multipoint linkage). However, when outliers for MAOB were removed, the significant evidence for linkage disappeared.

Chromosomes, Human, Pair 1↗

PubMed2002

Emergence and selection of RNA virus variants: memory and extinction.

Two features of viral quasispecies are reviewed: the presence of memory genomes as minority components of their mutant spectra, and viral extinction due to enhanced mutagenesis. Memory has been documented with several genetic markers of the important animal picornavirus foot-and-mouth disease virus (FMDV). The presence of memory genomes in viral quasispecies may accelerate their adaptive response whenever a selective constraint has already been experienced by a viral population during previous stages of its evolution. Enhanced mutagenesis has been shown to lead to losses of infectivity of a number of RNA viruses: poliovirus, vesicular stomatitis virus, human immunodeficiency virus type 1 and FMDV. These observations, based on the theoretical prediction of the existence of a copying error-threshold for maintenance of genetic information, may contribute to the development of a new antiviral strategy.

Animals↗

PubMed1999

LINEs, SINEs and repetitive DNA: non-LTR retrotransposons in plant genomes.

Retroelements and remnants thereof constitute a large fraction of the repetitive DNA of plant genomes. They include LTR (long terminal repeat) retrotransposons such as Ty1-copia and Ty3-gypsy retrotransposons, which are widespread in plant genomes and show structural similarity to retroviruses. Recently, non-LTR retrotransposons, lacking the long terminal repeats and subdivided into LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements), have been discovered as ubiquitous components of nuclear genomes in many species across the plant kingdom. LINEs are probably the most ancient class of retrotransposons in plant genomes, but the evolutionary borders between non-LTR retrotransposons, LTR retrotransposons and retroviruses are indistinct as shown by the detection of intermediate forms in other eukaryotic taxa. Transposition of non-LTR retrotransposons is only rarely observed in plants indicating that the majority of these retroelements are inactive and/or under regulation of the host genome. Transposition is poorly understood, but experimental evidence from other genetic systems, in particular from insect and mammalian species, shows that LINEs are able to transpose autonomously, while non-autonomous SINEs depend on the reverse transcription machinery of other retrotransposons. Fluorescence in situ hybridization demonstrated that different classes of retrotransposons differ largely in their chromosomal organization and are often excluded from blocks of rapidly homogenizing tandem repeats. In particular, LINEs contribute considerably to the repetitive DNA of nuclear plant genomes.

DNA, Plant↗

PubMed2003

Study on the evolution of the grande retrotransposon in the zea genus.

The study of Grande retrotransposon (RTN) variation reported here comprises the intrinsic element variability and the changes that element insertion provokes in the Zea genome, including its abundance among species. Sequence analysis of a defined long-terminal repeat (LTR) region from Grande RTN revealed a high level of sequence divergence since no identical sequences were found among the 65 clones examined that belong to different Zea species or maize inbred lines. Average diversity values within accessions ranged from 0.17 to 0.37 substitutions per nucleotide. Phylogenetic analysis revealed a lack of concordance between the phylogenetic tree obtained from LTR sequences and the conventional taxonomic tree, suggesting that different subfamilies of Grande elements existed before Zea speciation. When sequence-specific amplification polymorphism (SSAP) marker data, which combines genomic and RTN variation, are used, the derived trees reflect the established species phylogeny and allow, as well, differentiating among some maize lines. Finally, the evaluation of Grande abundance, using different element probes in all the Zea species but Z. luxurians, revealed around 5,700 copies per haploid genome in all the diploid species examined, indicating a similar expansion process of Grande in all the Zea genomes. This number of copies represents in all cases around a 3% of the genome, which implies that Grande RTN is an important component of the maize genome. The copy number ratio LTR/gag is around 2 in all the species analyzed, indicating that overwhelming majority of elements have internal region. Thus, mechanisms such as homologous recombination between LTRs of a single RTN, which would remove the internal region and one LTR, leaving behind a single recombinant LTR, seems not to be active in maize for Grande RTN.

Base Sequence↗

PubMed2004

Genome-wide comparison of the His-to-Asp phosphorelay signaling components of three symbiotic genera of Rhizobia.

Histidine-to-aspartate (His-Asp) phosphorelay (or two-component) systems are very common signal transduction mechanisms that are implicated in a wide variety of cellular responses to environmental stimuli. The His-Asp phosphorelay components include "sensor histidine kinase (HK)", "phosphotransfer intermediate (HPt)", and "response regulator (RR)". With special reference to three bacterial species (Mesorhizobium loti, Bradyrhizobium japonicum, Sinorhizobium meliloti), each of which belongs to a different genera of Rhizobia, here we attempted to compile all of the His-Asp phosphorelay components in order to reveal a comparative genome-wide overview as to the His-Asp phosphorelay. It was revealed that M. loti has 47 HKs, 1 HPts, and 58 RRs; B. japonicum has 80 HKs, 3 HPts, and 91 RRs; whereas S. meliloti has 40 HKs, 1 HPt, and 58 RRs. These His-Asp phosphorelay components were extensively compiled and characterized. The resulting overview as to the His-Asp phosphorelay of Rhizobia will provide us with a basis for understanding of the fundamental mechanisms underlying interactions between plants and microorganisms (including symbiosis), as well as nitrogen fixation.

Arabidopsis↗

PubMed1999

Genome-wide linkage analysis using genetic variance components of alcohol dependency-associated censored and continuous traits.

We used variance-components analysis to investigate the additive genetic effects regulating some of the phenotypes included in the GAW11 data set. Variance-components models were fitted using Gibbs sampling methods in BUGS v 0.6. Linkage analyses for both multivariate normal (MvN) traits and right censored survival times (age-of-onset) were based upon standard Haseman-Elston identity-by-descent sib-pair methods applied directly to traits showing evidence of substantial additive genetic determination (residualized for any important covariates) and to the estimated sigma A2 residuals for those traits. Harm avoidance behavior (TPQ subscale) showed evidence of linkage to markers on chromosomes 1, 13, and 18. P300 levels at the Fp1 site showed evidence of linkage to markers on chromosomes 2, 3, 9, 12, 17, 19, and 20. Platelet monoamine oxidase B (MAOB) levels showed evidence of linkage to D4S1651. The age-of-onset for ALDX1 in those over 30 years old showed evidence of linkage to markers on chromosomes 1, 6, 14, and 15. The age-of-onset for the more strictly defined ALDX2 in those over 30 years old showed evidence of linkage to markers on chromosomes 7 and 14. These results are consistent with a complex, multifactorial susceptibility to alcohol dependency.

Age of Onset↗

PubMed2003

New hepatitis B virus of cranes that has an unexpected broad host range.

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.

Animals↗

PubMed1997

A DNA primer associated with banana bunchy top virus.

Banana bunchy top virus (BBTV) genomic ssDNA is capable of complementary strand synthesis in vitro without the addition of exogenous primers. We have demonstrated that the self-priming of BBTV can be attributed to a population of endogenous primers which are bound to the genomic DNA within the virions. The primer molecules appeared to be composed entirely of DNA and are heterogeneous in size. The primers were cloned, sequenced and shown to map to a region within the major common region and extend 5' of this conserved region. These primers were found to be associated with multiple components of the genome and were capable of full-length complementary strand synthesis in vitro. Interestingly, most of the cloned primers appeared to be derived from BBTV DNA-5; no function has yet been determined for the putative protein of the large ORF within this component.

Base Sequence↗

PubMed2006

Nutrigenomics: integrating genomic approaches into nutrition research.

It has been suggested that the supermarket of today will be the pharmacy of tomorrow. Such statements have been derived from recognition of our increasing ability to optimize nutrition, and maintain a state of good health through longer periods of life. The new field of nutrigenomics, which focuses on the interaction between bioactive dietary components and the genome, recognizes that current nutritional guidelines may be ideal for only a relatively small proportion of the population. There is good evidence that nutrition has significant influences on the expression of genes, and, likewise, genetic variation can have a significant effect on food intake, metabolic response to food, individual nutrient requirements, food safety, and the efficacy of disease-protective dietary factors. For example, a significant number of human studies in various areas are increasing the evidence for interactions between single nucleotide polymorphisms (SNPs) in various genes and the metabolic response to diet, including the risk of obesity. Many of the same genetic polymorphisms and dietary patterns that influence obesity or cardiovascular disease also affect cancer, since overweight individuals are at increased risk of cancer development. The control of food intake is profoundly affected by polymorphisms either in genes encoding taste receptors or in genes encoding a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. Total dietary intake, and the satiety value of various foods, will profoundly influence the effects of these genes. Identifying key SNPs that are likely to influence the health of an individual provides an approach to understanding and, ultimately, to optimizing nutrition at the population or individual level. Traditional methods for identification of SNPs may involve consideration of individual variants, using methodologies such as restriction fragment length polymorphisms or quantitative real-time PCR assays. New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches.

Chronic Disease↗

PubMed1983

DNA sequence of the US component of the varicella-zoster virus genome.

The linear duplex DNA molecule of varicella-zoster virus is 120 000 bp in size and has the sequence arrangement UL-IRS-US-TRS, where UL and US are unique sequences and IRS and TRS are inverted repeats flanking US. The primary structure of the cloned SstI g DNA fragment containing US (5232 bp) and adjacent portions of IRS and TRS (426 bp of each) was determined, and the following model for genetic expression was derived from an analysis of the sequence. The region specifies four mRNAs encoding primary translation products with mol. wts. of 11, 44, 39 and either 74 or 70 kd. The 39-and 70-kd proteins have primary structures characteristic of membrane proteins. The mRNAs encoding the 11- and 74/70-kd proteins extend from opposite sides of US into IRS/TRS, thus sharing a common 3' terminus. These proteins do not share a common carboxy terminus because the coding region for the 11-kd protein terminates at the junction between US and IRS, whereas that for the 74/70-kd protein extends into TRS. The analysis affirms the hypothesis that the extent of inverted repeats in herpesvirus genomes is primarily a result of constraints imposed by adjacent protein coding sequences.

Amino Acid Sequence↗