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At least 1,189 records · Page 66Linked to original sources
PubMed2005

Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.

We attempted to characterize the genes expression of CD4+ T lymphocytes for the pathogenesis of systemic lupus erythematosus (SLE). Genomewide gene expression profiles of CD4+ T cells, which were isolated from the disease severe activity (T4-1s) and nonactivity (T4-2s) with an SLE patient by using long serial analysis of gene expression (LongSAGE). We picked out 289 genes matching to Unigene cluster with different expression more than four copies between T4-1s and T4-2s libraries and analyzed their roles from the collectedly published articles of PubMed by genes functional clustering. The genes functions were related to a diverse cellular process including: (1) most of these genes were associated with CD4+ T cells functions, particularly related to cellular developments; (2) Ras pathway genes as RANBP10, GMIP, RASGRP2 and ARL5 might be responsible for the abnormal development of CD4+ T cells of SLE; (3) HIG2, TCF7, KHSRP, WWP1, SMAD3, TLK2, AES, CCNI and PIM2 belong to Wnt/beta-catenin way, they could play roles in modulating proliferation and differentiation of T lymphocytes; (4) uncertain viral infections may initiate autoimmunity because high levels expression genes were detected in T4-1s such as TRIM22, IER2, ABCE1, DUT, G1P2, G1P3, HNRPUL1, EVER2, IFNAR1, TNFSF14, TMP21 and PVRL2; and (5) apoptosis relating genes as EIF3S8, SH3BGRL3, GPX4, TOSO, PFDN5, BIN1, XIAPAF1, TEGT and CUGBP2 may contribute to over uploading of selfantigens in SLE cells. Abnormalities findings of multiple genes expression involving with a variety of CD4+ T cells process might be meaningful to understanding the pathogenesis of SLE, and immature CD4+ T cells may be responsible for SLE.

Adult↗
PubMed2004

Exercise training improves cardiac function-related gene levels through thyroid hormone receptor signaling in aged rats.

Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca(2+)-ATPase, which participate in the regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca(2+)-ATPase. We hypothesized that myocardial TR signaling contributes to a molecular mechanism of exercise training-induced improvement of MHC and SR Ca(2+)-ATPase genes with cardiac function in old age. We investigated whether TR signaling and gene expression of MHC and SR Ca(2+)-ATPase in the aged heart are affected by exercise training, using the hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and trained aged rats (23 mo old, swimming training for 8 wk). Trained aged rats showed improvement in cardiac function. Expression of TR-alpha1 and TR-beta1 proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats. The activity of TR DNA binding to the transcriptional regulatory region in the alpha-MHC and SR Ca(2+)-ATPase genes and the mRNA and protein expression of alpha-MHC and SR Ca(2+)-ATPase in the heart and plasma 3,3'-triiodothyronine and thyroxine levels were altered in association with changes in the myocardial TR protein levels. These findings suggest that exercise training improves the aging-induced downregulation of myocardial TR signaling-mediated transcription of MHC and SR Ca(2+)-ATPase genes, thereby contributing to the improvement of cardiac function in trained aged hearts.

Aging↗
PubMed2005

Floral patterning in Lotus japonicus.

Floral patterning in Papilionoideae plants, such as pea (Pisum sativum) and Medicago truncatula, is unique in terms of floral organ number, arrangement, and initiation timing as compared to other well-studied eudicots. To investigate the molecular mechanisms involved in the floral patterning in legumes, we have analyzed two mutants, proliferating floral meristem and proliferating floral organ-2 (pfo-2), obtained by ethyl methanesulfonate mutagenesis of Lotus japonicus. These two mutants showed similar phenotypes, with indeterminate floral structures and altered floral organ identities. We have demonstrated that loss of function of LjLFY and LjUFO/Pfo is likely to be responsible for these mutant phenotypes, respectively. To dissect the regulatory network controlling the floral patterning, we cloned homologs of the ABC function genes, which control floral organ identity in Arabidopsis (Arabidopsis thaliana). We found that some of the B and C function genes were duplicated. RNA in situ hybridization showed that the C function genes were expressed transiently in the carpel, continuously in stamens, and showed complementarity with the A function genes in the heterogeneous whorl. In proliferating floral meristem and pfo-2 mutants, all B function genes were down-regulated and the expression patterns of the A and C function genes were drastically altered. We conclude that LjLFY and LjUFO/Pfo are required for the activation of B function genes and function together in the recruitment and determination of petals and stamens. Our findings suggest that gene duplication, change in expression pattern, gain or loss of functional domains, and alteration of key gene functions all contribute to the divergence of floral patterning in L. japonicus.

Amino Acid Sequence↗
PubMed1992

The function of the neurogenic genes during epithelial development in the Drosophila embryo.

The complex embryonic phenotype of the six neurogenic mutations Notch, mastermind, big brain, Delta, Enhancer of split and neuralized was analyzed by using different antibodies and PlacZ markers, which allowed us to label most of the known embryonic tissues. Our results demonstrate that all of the neurogenic mutants show abnormalities in many different organs derived from all three germ layers. Defects caused by the neurogenic mutations in ectodermally derived tissues fell into two categories. First, all cell types that delaminate from the ectoderm (neuroblasts, sensory neurons, peripheral glia cells and oenocytes) are increased in number. Secondly, ectodermal tissues that in the wild type form epithelial structures lose their epithelial phenotype and dissociate (optic lobe, stomatogastric nervous system) or show significant differentiative abnormalities (trachea, Malpighian tubules and salivary gland). Abnormalities in tissues derived from the mesoderm were observed in all six neurogenic mutations. Most importantly, somatic myoblasts do not fuse and/or form an aberrant muscle pattern. Cardioblasts (which form the embryonic heart) are increased in number and show differentiative abnormalities; other mesodermal cell types (fat body, pericardial cells) are significantly decreased. The development of the endoderm (midgut rudiments) is disrupted in most of the neurogenic mutations (Notch, Delta, Enhancer of split and neuralized) during at least two stages. Defects occur as early as during gastrulation when the invaginating midgut rudiments prematurely lose their epithelial characteristics. Later, the transition of the midgut rudiments to form the midgut epithelium does not occur. In addition, the number of adult midgut precursor cells that segregate from the midgut rudiments is strongly increased. We propose that, at least in the ectodermally and endodermally derived tissues, neurogenic gene function is primarily involved in interactions among cells that need to acquire or to maintain an epithelial phenotype.

Animals↗
PubMed1986

Local function of the Notch gene for embryonic ectodermal pathway choice in Drosophila.

Mutations at the Notch locus affect the fate of cells in the neurogenic region of the Drosophila embryo so that epidermal precursors become neuroblasts. We have analyzed the cellular requirements for wild-type Notch gene function by means of genetic mosaics, using a cuticle marker to distinguish hypodermal cell genotype. Cells that were genotypically Notch never gave rise to hypoderm within the neurogenic region of mosaic embryos. Mosaic dividing lines within the neurogenic region juxtapose N+ hypoderm with regions of neural hypertrophy. This autonomous action of Notch in hypodermal cells is consistent with a local function of the protein during neurogenesis. Comparison of clone distribution in Notch mosaics and controls suggests that islands of wild-type hypodermal cells fail to differentiate cuticle.

Animals↗
PubMed1984

Mutations affecting functions of the Drosophila gene glued.

Glued mutations in Drosophila comprise an essential complementation group with complex developmental effects. The original Glued mutation (Gl) has dominant nonlethal effects in heterozygous flies, principally on the morphogenesis of the visual system. Gl also has a recessive lethal effect early in development. Mutations that reverse the dominant visual effects of Gl (GlR mutations) were induced by gamma-radiation or by insertions of the transposable P element. The GlR(G) mutations induced by gamma-radiation do not reverse the lethal effect of Gl; these appear to be null mutations, some of which (and possibly all) delete segments of the Glued region. The GlR(P) mutations induced by insertion of the P element also reverse concomitantly a recessive lethal effect of Gl, suggesting that both the recessive and dominant effects are controlled by the same gene. The reversal of a lethal effect of Gl by the P element is remarkable, since it indicates that an essential gene function can be restored by insertion of unrelated DNA. Another class of lethal Glued mutations was induced in the normal Gl+ strain by ethyl methanesulfonate (EMS). The EMS mutations belong to the same essential complementation group as Gl, but do not have the strong dominant effects of Gl on the visual system. The GlR(P) mutations provide a molecular marker for the Glued gene, which was used to map the gene to the 70C2 band of chromosome 3L by in situ hybridization of a P element probe to polytene chromosomes from the GlR(P) strains and also to isolate clones of Glued genomic DNA for molecular studies of the normal gene and the various Glued mutations.

Animals↗
PubMed1989

Analysis of the promoter of the Autographa californica nuclear polyhedrosis virus p10 gene.

Functional analyses of the p10 gene promoter from the Autographa californica nuclear polyhedrosis virus (AcNPV) were performed by progressively deleting the 230 nucleotides upstream from the p10 coding sequences towards the ATG codon. Truncated promoter sequences retaining the full 5' non-coding leader of p10 were inserted in front of the chloramphenicol acetyltransferase (CAT) gene, and promoter activity in transfected AcNPV-infected cells was measured using the transient CAT expression assay. The removal of sequences to a position 101 nucleotides upstream from the p10 ATG did not affect the level of CAT expression. Deletion of a further 13 nucleotides reduced CAT expression by three- to fourfold, but the removal of three more nucleotides, which deleted most of the baculovirus very late gene transcription consensus sequence, almost completely abolished activity. The removal of the TATA motif had no effect on the level of transient expression. We conclude that a sequence of about 101 nucleotides upstream from the ATG codon of p10 is sufficient for high level promoter activity in this transient system.

Animals↗
PubMed1995

Functional analysis of the 5' flanking sequence in the ovine beta 1-adrenergic receptor gene.

Functional data for the promoter of the beta 1-adrenergic receptor (beta 1AR) gene are lacking. We previously cloned the ovine beta 1AR gene and mapped the transcription start sites. We now report data on ovine beta 1AR gene expression obtained by transient transfection. Progressive deletion of upstream 5' flanking region moderately increased transcription activity in three cell lines compared to the full-length promoter. Deletion of sequences between -1530 and -953 produced the greatest increase in transcriptional activity. This region encompassed a putative GRE and an AP1 site. Deletion of the transcription start sites eliminated nearly all of the activity. Dexamethasone significantly increased activity of each of the promoter constructs tested in C6 glioma cells and an embryonic myocardial cell line, W1 cells. T3 alone had no effect and cotreatment with T3 did not augment the effects of dexamethasone. We conclude, basal transcription activity is repressed by a mechanism which operates through element(s) in the proximal promoter. Glucocorticoids increase transcription through mechanism(s) within the same region. We speculate that this region in the ovine beta 1AR promoter may be responsible for its unique transcription regulation.

Animals↗
PubMed1981

The cloning and reintroduction into animal cells of a functional CAD gene, a dominant amplifiable genetic marker.

Rodent cells resistant to PALA, a specific inhibitor of the aspartate transcarbamylase activity of the multifunctional CAD protein, overproduce CAD as a result of amplification of the CAD gene. We cloned a functional CAD gene from Syrian hamster cells using a cosmid vector. Two independently isolated cosmids containing CAD genes have inserts 40 and 45 kb long. We introduced the cloned genes into CAD-deficient Chinese hamster ovary (CHO) cell mutants by fusing them with protoplasts of Escherichia coli containing the cosmids. We also introduced the cloned genes into wild-type CHO cells by selecting cells that became resistant to high concentrations of PALA following protoplast fusion. The transformants of the mutant and wild-type CHO cells contain multiple active copies of the donated Syrian hamster CAD genes. The cloned genes in three independent transformants are integrated into host-cell chromosomes at single locations identified by in situ hybridization. In two of these transformants, the genes are located in one X chromosome or in a chromosome resembling the X. In the third case, the genes are located in a small metacentric or rearranged chromosome.

Animals↗
PubMed1999

Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA.

Development of methods that allow an efficient expression of exogenous genes in animals would provide tools for gene function studies, treatment of diseases and for obtaining gene products. Therefore, we have developed a hydrodynamics-based procedure for expressing transgenes in mice by systemic administration of plasmid DNA. Using cDNA of luciferase and beta-galactosidase as a reporter gene, we demonstrated that an efficient gene transfer and expression can be achieved by a rapid injection of a large volume of DNA solution into animals via the tail vein. Among the organs expressing the transgene, the liver showed the highest level of gene expression. As high as 45 microg of luciferase protein per gram of liver can be achi- eved by a single tail vein injection of 5 microg of plasmid DNA into a mouse. Histochemical analysis using beta-galactosidase gene as a reporter reveals that approximately 40percent of hepatocytes express the transgene. The time-response curve shows that the level of transgene expression in the liver reaches the peak level in approximately 8 h after injection and decreases thereafter. The peak level of gene expression can be regained by repeated injection of plasmid DNA. These results suggest that a simple, convenient and efficient method has been developed and which can be used as an effective means for studying gene function, gene regulation and molecular pathophysiology through gene transfer, as well as for expressing proteins in animals.

Animals↗
PubMed2003

Cloning and functional analysis of aniline dioxygenase gene cluster, from Frateuria species ANA-18, that metabolizes aniline via an ortho-cleavage pathway of catechol.

Genes encoding an aniline dioxygenase of Frateuria sp. ANA-18, which metabolizes aniline via the ortho-cleavage pathway of catechol, were cloned and named tdn genes. The tdn genes were located on the chromosomal DNA of this bacterium and weren't clustered with catechol-degrading gene clusters. These results show that the ANA-18 aniline-degrading gene cluster is constructionally different from Pseudomonas tdn and Acinetobacter atd gene clusters, which degrade aniline via the meta-cleavage pathway of catechol and organize catechol-metabolic genes in the gene clusters. When cloned tdnQTA1A2B genes were expressed in Eschherichia coli, aniline dioxygenase activity was observed. Southern blot analysis revealed that homologues of the tdnA1A2B genes didn't exist in strain ANA-18. Disruption of the tdnA1A2 genes gave the parent strain ANA-18 a defect in aniline metabolism. On the basis of these results, we concluded that only the cloned tdn genes function as genes encoding aniline dioxygenase in strain ANA-18 although this bacterium had two catechol-degrading gene clusters.

Aniline Compounds↗
PubMed1980

Coordinate expression of Escherichia coli dnaA and dnaN genes.

The defects of temperature-sensitive dnaA and dnaN mutants of Escherichia coli are complemented by a recombinant lambda phage, which carries the bacterial DNA segment composed of two EcoRI segments of 1.0 and 3.3 kilobases. Derivatives of the phage, which have an insertion segment of Tn3 in the dnaA gene, are much less active in expressing the dnaN gene function than the parent phage. The dnaN gene activity was determined as the efficiency of superinfecting phage to suppress loss of the viability of lambda lysogenic dnaN59 cells at the non-permissive temperature. Deletions that include the end of the dnaA gene distal to the dnaN gene also reduce the expression of the dnaN gene function. Deletion and insertion in the dnaN gene do not affect the expression of the dnaA gene function. The expression of the dnaN gene function by the dnaA- dnaN+ phages remains weak upon simultaneous infection with dnaA+ dnaN- phages. Thus the insertion and deletion of the dnaA gene influence in cis the expresion of the dnaN gene. We propose that the dnaA and dnaN genes constitute an operon, where the former is upstream to the latter.

Bacteriophage lambda↗
PubMed2001

Identification of partial loss of function p53 gene mutations utilizing a yeast-based functional assay.

Missense mutations within the central DNA binding region of p53 are the most prevalent mutations found in human cancer. Numerous studies indicate that 'hot-spot' p53 mutants (which comprise approximately 30% of human p53 gene mutations) are largely devoid of transcriptional activity. However, a growing body of evidence indicates that some non-hot-spot p53 mutants retain some degree of transcriptional activity in vivo, particularly against strong p53 binding sites. We have modified a previously described yeast-based p53 functional assay to readily identify such partial loss of function p53 mutants. We demonstrate the utility of this modified p53 functional assay using a diverse panel of p53 mutants.

Base Sequence↗
PubMed2003

A genomics approach to crop pest and disease research.

Genome-wide analyses of gene function and gene expression are beginning to yield valuable information in many areas of biological research, and these genomic tools are now being applied to crop pest and disease research. DNA sequencing of cDNA libraries to generate sets of expressed sequence tags (ESTs) are allowing gene compendiums for crop diseases to be compiled. Annotation of such data collections is also providing a wealth of functional information about gene products through similarities to proteins with known function. The next phase of the functional genomics era will be to employ large-scale techniques to knock out or silence genes in order to synthesize gene-specific mutants for phenotypic analysis and to use micro-array methodology to analyze global gene expression, protein turnover and protein processing during the processes of parasitism and colonization. Application of these technologies promises to accelerate the pace that biological information relevant to crop protection accrues. The ability of researchers to assimilate this information into complex models and workable hypotheses is, thus, set to revolutionize the way we study pests and diseases of crop plants.

Crops, Agricultural↗
PubMed2004

Function of the Trithorax-like gene during Drosophila development.

Maintenance of homeotic gene expression during Drosophila development relies on the Polycomb and the trithorax groups of genes. Classically, the Polycomb proteins act as repressors of homeotic gene function, whereas trithorax proteins function as activators. However, recent investigation has indicated that some of these maintenance genes may act both as repressors and activators. One of those is the Drosophila Trithorax-like gene that codes for the GAGA factor. To investigate its dual activator/repressor role, we have studied the function of the Trithorax-like throughout Drosophila development. Embryos lacking both the maternal and the zygotic Trithorax-like function do not develop suggesting that Trithorax-like might be required in oogenesis. Homozygous Trithorax-like null mutant embryos show reduced expression levels of some of the homeotic proteins. Trithorax-like mutant larval clones, however, do not show phenotypes indicative of either activation or repression of homeotic gene function. These results suggest that Trithorax-like is required during embryogenesis but not throughout larval development for the regulation of homeotic gene expression. Moreover, this temporal requirement seems also to regulate MCP-mediated silencing. Finally, lack of Trithorax-like function modulates the gain of function phenotypes caused by over-expression of homeotic genes. To explain Trithorax-like gene function, we propose a model where very early in development, GAGA factor probably establishes a chromatin ground state for transcription. The differential "on/off" transcriptional state of the homeotic genes is then established and propagated by the action of the specific regulatory proteins independently of the GAGA factor. We also suggest that GAGA factor may not have a dual activator/repressor function. Rather, Trithorax-like mutations may produce dual loss of activation and loss of repression effects.

Animals↗
PubMed2002

Mammalian sperm proteins are rapidly evolving: evidence of positive selection in functionally diverse genes.

A growing number of genes involved in sex and reproduction have been demonstrated to be rapidly evolving. Here, we show that genes expressed solely in spermatozoa represent a highly diverged subset among mouse and human tissue-specific orthologs. The average rate of nonsynonymous substitutions per site (K(a)) is significantly higher in sperm proteins (mean K(a) = 0.18; N = 35) than in proteins expressed specifically in all other tissues (mean K(a) = 0.074; N = 473). No differences, however, are found in the synonymous substitution rate (K(s)) between tissues, suggesting that selective forces, and not mutation rate, explain the high rate of replacement substitutions in sperm proteins. Four out of 19 sperm-specific genes with characterized function demonstrated evidence of strong positive Darwinian selection, including a protein involved in gene regulation, Protamine-1 (PRM1), a protein involved in glycolysis, GAPDS, and two egg-binding proteins, Adam-2 precursor (ADAM2) and sperm-adhesion molecule-1 (SAM1). These results demonstrate the rapid evolution of sperm-specific genes and highlight the molecular action of sexual selection on a variety of characters involved in mammalian sperm function.

Amino Acid Substitution↗
PubMed1999

Human and mouse XAP-5 and XAP-5-like (X5L) genes: identification of an ancient functional retroposon differentially expressed in testis.

Although most retroposons that arose by reverse transcription of cellular mRNAs and by reintegration into the genome are nonfunctional, several examples exist in which the retroposon acquired a novel function and became fixed in the genome as a functional gene. We identified another such case: the ubiquitously expressed X-linked XAP-5 gene with unknown function gave rise to its retroposed counterpart, XAP-5-like (X5L), which has an intronless open reading frame and is autosomal in human. Phylogenetic analysis of the human and mouse XAP-5 and X5L genes shows that the retroposition most likely took place before the radiation of eutherian mammals. The XAP-5 and X5L genes are expressed in a wide range of tissues but are differentially expressed in testis. The ancient origin and broad expression of the X5L retroposon indicate that the XAP-5 and X5L genes may have assumed different functions in somatic cells. In addition to this, because of its autosomal location and its high level and particular pattern of expression in spermatogenic cells, the X5L expression in testis may compensate for the X-linked XAP-5 gene, which may be silenced during spermatogenesis.

Amino Acid Sequence↗
PubMed1993

The human GRB2 and Drosophila Drk genes can functionally replace the Caenorhabditis elegans cell signaling gene sem-5.

Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling processes involved in guiding a class of cell migrations and inducing vulval cell fates. The sem-5 sequence encodes a protein comprised almost exclusively of SH2 and SH3 domains (SH, src homology region) that are found together in many signaling proteins and nonreceptor tyrosine kinases. A human protein, GRB2, was identified by its ability to associate with the activated human epidermal growth factor receptor (hEGFR). The GRB2 and Sem-5 proteins share an identical architecture of their SH2 and SH3 domains and 58% amino acid sequence identity. Here we demonstrate that GRB2 and a Drosophila sem-5-like gene Drk can specifically rescue sem-5 mutants. We also show that Sem-5, like GRB2, can bind to the activated hEGFR in vitro. We further correlate the abilities of several mutant variants of GRB2 and Sem-5 to bind to the hEGFR in vitro with their abilities to functionally replace sem-5 in vivo. These data indicate that GRB2 and Drk are functional homologues of Sem-5 and demonstrate the high degree of conservation of both structure and function between signaling systems throughout evolution.

Adaptor Proteins, Signal Transducing↗