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At least 595 records · Page 33Linked to original sources
PubMed2005

Gene expression profiling in rice young panicle and vegetative organs and identification of panicle-specific genes through known gene functions.

In rice, at the stage from pistil and stamen primordia formation to microsporocyte meiosis, the young panicle organs (YPO) make a great contribution to grain productivity. This period corresponds to the onset of meiosis and marks the transition from vegetative to reproductive stages. By comparing gene expression profiling of YPO with that of rice aerial vegetative organs (AVO), it is possible to gain further molecular insight into this period that is developmentally and functionally important. In this report, a total of 92,582 high-quality ESTs from 5'-end sequencing, including 44,247 from YPO and 48,335 from AVO, were obtained and classified. There were 12,884 (29.12%) ESTs from YPO and 16,304 (33.73%) ESTs from AVO matched to known genes, which generated 1,667 and 2,172 known genes, respectively, after integration of these ESTs. From the functions of known homologous genes, we identified some tissue- and developmental-stage-specified genes in YPO. The expression of these genes clearly reflected the unique functional characteristics of YPO. Furthermore, we estimated that there are about 10,000 mRNAs specifically expressed in rice YPO.

DNA Primers↗
PubMed2000

N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function.

The role of long-chain polyunsaturated fatty acids (PUFA) in the etiopathology and treatment of cancer is poorly understood. We have studied the effects of n;-3 and n;-6 PUFA on the proliferation and survival of normal human uroepithelial (NHU) cells, cells with disabled p53 function after stable transfection with the human papillomavirus 16 (HPV16) E6 gene (HU-E6), and p53-disabled cells that had passed through crisis and acquired karyotypic abnormalities (HU-E6P). The n;-3 and n;-6 PUFA had distinct reversible antiproliferative and irreversible cytostatic effects according to concentration and exposure time. The reversible antiproliferative effect was partly due to the production of lipoxygenase metabolites. NHU and HU-E6 cells were equally sensitive to n;-3 and n;-6 PUFA, but HU-E6P cells were more resistant to both the antiproliferative and cytostatic effects. Cytostatic concentrations of n;-3 and n;-6 PUFA did not induce apoptosis, but caused permanent growth arrest ("interphase" or "reproductive" cell death) and mRNA levels for genes involved in cell cycle control (p21, p16, p27, cdk1, cdk2, and cdk4) were not altered. Neither n;-3 nor n;-6 PUFA promoted acquisition of karyotypic abnormalities in HU-E6 cells, suggesting that n;-3 and n;-6 PUFA do not cause genotoxic damage. In conclusion, our studies show that the antiproliferative and cytostatic effects of n;-3 and n;-6 PUFA are not dependent on p53 function and, further, that transformation results in a loss of sensitivity to n;-3 and n;-6 PUFA-mediated growth inhibition.

Apoptosis↗
PubMed1974

Analysis of bacteriophage phi 29 gene function: protein synthesis in suppressor-sensitive mutant infection of Bacillus subtilis.

Phage phi29 suppressor-sensitive (sus) mutants of 14 cistrons have been examined for production of (14)C-labeled viral-specific proteins in restrictive infections of Bacillus subtilis. Proteins specified by four cistrons (H, J, L, and N) have been resolved and identified by sodium dodecyl sulfate gel electrophoresis and autoradiography, and fragments of the normal polypeptides were detected. Mutants of six cistrons (C, D, E, F, I, and M) demonstrated two or more missing bands in the gel profiles, and thus some of these gene products may have regulatory functions. Mutation was detected in at least five genes coding for low-molecular-weight proteins, but a conditionally lethal mutant in only one of these genes has been isolated. Preliminary evidence that a precursor protein is cleaved to generate the neck appendage structural protein and a low-molecular-weight product has been obtained.

Amino Acids↗
PubMed2002

SVISS - a novel transient gene silencing system for gene function discovery and validation in tobacco plants.

We developed a novel, two-component transient gene silencing system in which the satellite tobacco mosaic virus (STMV) is used as vector for the delivery of inhibitory RNA into tobacco plants and the tobacco mosaic virus strain U2 (TMV-U2) is used as helper virus for supplying replication and movement proteins in trans. The main advantage of the system is that by uncoupling virus replication components from silencing induction components, the intensity of silencing becomes more pronounced. We call this system satellite virus-induced silencing system (SVISS) and will demonstrate here its robustness, speed and effectiveness. We were able to obtain pronounced and severe knockout phenotypes for a range of targeted endogenous genes belonging to various biochemical pathways and expressed in different plant tissues, such as genes involved in leaf and flower pigmentation, genes for cell wall synthesis in leaf, stem and root tissues or a ubiquitous RNA polymerase gene. By tandem insertion of more than one target gene sequence into the vector, we were able to induce simultaneous knockouts of an endogenous gene and a transgene. SVISS is the first transient gene silencing system for Nicotiana tabacum, which is a genetically well-characterized bridging species for the Solanaceae plant family.

Gene Expression Regulation, Plant↗
PubMed1985

Graft rejection in a congenic panel of rats with defined immune response genes for class I antigens. II. Quantitative aspects of Ir gene function in a full-haplotype mismatch.

Previous studies have shown that the Ir-gene-controlled rejection of rl tissues by c/u responder and non-rejection by c low responders does not extend to tissues expressing a full a haplotype mismatch. However, antibody responses and liver graft rejection are both defective in low responders, even across a full haplotype barrier. We have therefore used a titrated adoptive transfer assay to search for quantitative differences in the responsiveness of c and c/u animals to a organ grafts. We first established that a heart graft rejection could be ablated in both recipient strains with whole-body irradiation and could be restored with syngeneic cells. Titration of restorative cells revealed that 5 times as many c cells were required to restore graft rejection in c recipients as c/u cells were required in c/u recipients. Use of cells from primed donors showed that in both c/u and c animals these cells had undergone about a 5-fold increase in potency, showing that there was no failure of proliferation and differentiation in the low responder after contact with antigens. Cross-transfer experiments were done to attempt to localize the defect in low-responder animals either to a failure of low-responder antigen-presenting cells (APC) to trigger a response or a defect in the responsiveness of alloreactive cells toward the a antigens. In these experiments c cells were obtained from radiation chimeras of the c----c/u type. These cells were used to restore graft rejection in c/u irradiated recipients. Similar experiments employing c/u cells obtained from c/u----c chimeras and given to irradiated c recipients were also done. These showed that c cells from chimeras were marginally less potent than c/u cells from chimeras. In contrast when cross-transfer of c/u cells to c animals bearing a nonrejected rl heart was done, no rejection was seen even when antigen presenting cells were cotransferred. The conclusions from this series of experiments were that quantitatively small defects were present in both repertoire and antigen presentation, and that these quantitative defects in aggregate were probably sufficient to explain the documented low responsiveness of c animals to the a haplotype. The failure of high-responder c/u cells to secure rejection of rl tissues in the low-responder c environment suggests that presentation of isolated class I differences in host APCs is mandatory for rejection to occur and is highly defective in the c animal.

Animals↗
PubMed1986

Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression.

A chimeric gene was constructed in which sequences between 2,000 base pairs upstream of the start of transcription of the mouse alpha 2(I) collagen gene and 54 base pairs downstream of this site were fused to the chloramphenicol acetyltransferase (CAT) gene. We present evidence suggesting that this collagen gene segment is sufficient for cell-specific expression of the chimeric gene. Indeed, the levels of CAT activity in transient expression experiments were at least 10 times higher after transfection of NIH 3T3 cells than after transfection of a mouse myeloma cell line, whereas much less difference was found after transfection of these two cell types with pSV2-CAT, a plasmid in which the early simian virus 40 promoter is fused to the CAT gene. Several deletions were introduced in the same 5'-flanking segment of the alpha 2(I) collagen gene, and the effects of these deletions were examined after DNA transfection of the chimeric collagen-CAT gene into NIH 3T3 cells. At least two segments broadly located between -979 and -502 and between -346 and -104 are needed for optimal expression of the chimeric gene. These results were obtained both in transient expression experiments and by analysis of pools of NIH 3T3 cells that were stably transfected with the different mutants. In general, the effects of the deletions on the activity of the alpha 2(I) collagen promoter were analogous, whether the plasmids harbored the simian virus 40 enhancer sequence or not, although the overall levels of expression of the chimeric gene were increased when the recombinant plasmids contained this sequence.

Animals↗
PubMed2006

Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells.

Human pituitary tumor-transforming gene 1 (PTTG1) encodes a securin protein critically important in regulating chromosome separation. Murine PTTG (mPTTG) is 66% homologous to human PTTG1 and PTTG-null (PTTG-/-) mice exhibit pancreatic beta-cell hypoplasia and abnormal nuclear morphology with resultant diabetes. As we show that ductal beta-cell neogenesis is intact in PTTG-/- mice, we explored mechanism for defective beta-cell replication. We tested whether mPTTG exhibits securin properties in mouse insulin-secreting insulinoma MIN6 cells, using a live-cell system to monitor mitosis in cells transfected with an enhanced green fluorescent protein (EGFP)-tagged mPTTG conjugate (mPTTG-EGFP). To fulfill the criteria for securin properties, the protein should undergo degradation immediately before the metaphase-to-anaphase transition when expression levels are low, and should inhibit metaphase-to-anaphase transition when expression levels are high. EGFP itself did not undergo degradation throughout mitosis and high levels of EGFP per se did not affect normal mitosis progression (n=25). However, mPTTG-EGFP was degraded 2 min before the metaphase-to-anaphase transition when expression levels were low (n=19), and high mPTTG-EGFP levels blocked metaphase-to-anaphase transition in 13 cells. mPTTG-EGFP inhibited MIN6 cell proliferation and caused apoptosis. Immunocoprecipitation demonstrated binding of mPTTG-EGFP and separase. These results show that mPTTG exhibits properties consistent with a murine securin in insulin-secreting mouse cells and mPTTG overexpression inhibits cell proliferation, suggesting that defective beta-cell proliferation observed in PTTG-/- mice is likely due to abnormal cell-cycle progression.

Anaphase↗
PubMed1972

Histocompatibility-linked immune response gene function in guinea pigs. Specific inhibition of antigen-induced lymphocyte proliferation by alloantisera.

A number of autosomal dominant immune response (IR) genes have been identified in both mice and guinea pigs. These IR genes have been shown to be linked to the major histocompatibility antigens of the species and to be functionally expressed primarily in T lymphocytes. In order to more fully understand the relationship between IR genes, histocompatibility antigens, and immune recognition, the effect of specific alloantisera on lymphocyte stimulation induced by antigens under control of IR genes was examined. Using lymphocytes from strain 2 or strain 13 animals, the in vitro proliferative responses both to antigens which are known to be under genetic control (DNP-GL in strain 2 guinea pigs and GT in strain 13 guinea pigs) and to an antigen which is not known to be under genetic control (PPD) were inhibited to a similar degree and to a much greater extent than the response to phytohemagglutinin. However, when cells from F(1) (2 x 13) animals are used, the alloantisera markedly inhibit only the response which is linked to the histocompatibility antigens against which the serum is directed. Thus, the anti-2 serum inhibited the response to DNP-GL but not to GT; the anti-13 serum inhibited the response to GT but did not affect DNP-GL response. The inhibitory activity of the alloantisera could not be removed by absorption with gamma globulin of the opposite strain. It can be concluded from these observations that immune response genes produce a cell surface-associated product and that this product plays a role in the mechanism of antigen recognition by the T lymphocyte. The mechanisms by which alloantisera block this process of antigenic recognition is not resolved nor is the relationship between the IR gene product and the antigen-binding receptor of the T lymphocyte. The approach described here offers a powerful tool for the resolution of these problems.

Animals↗
PubMed2006

A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma.

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers.

Brain Neoplasms↗
PubMed2002

LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer.

The Pseudomonas aeruginosa LasR protein functions in concert with N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C(12)-HSL) to coordinate the expression of target genes, including many genes that encode virulence factors, with cell density. We used a LexA-based protein interaction assay to demonstrate that LasR forms multimers only when 3O-C(12)-HSL is present. A series of LasR molecules containing internal deletions or substitutions in single, conserved amino acid residues indicated that the N-terminal portion of LasR is required for multimerization. Studies performed with these mutant versions of LasR demonstrated that the ability of LasR to multimerize correlates with its ability to function as a transcriptional activator of lasI, a gene known to be tightly regulated by the LasR-3O-C(12)-HSL regulatory system. A LasR molecule that carries a C-terminal deletion can function as a dominant-negative mutant in P. aeruginosa, as shown by its ability to decrease expression of lasB, another LasR-3O-C(12)-HSL target gene. Taken together, our data strongly support the hypothesis that LasR functions as a multimer in vivo.

Bacterial Proteins↗
PubMed1998

Requirement for Xvent-1 and Xvent-2 gene function in dorsoventral patterning of Xenopus mesoderm.

Xvent-1 and Xvent-2 are members of a novel homeobox subfamily that have been implicated in dorsoventral patterning in Xenopus mesoderm and are thought to function in BMP signalling. Here we investigate the requirement for Xvent function by employing two dominant-negative strategies. Loss of Xvent function dorsalizes ventral mesoderm, induces secondary embryonic axes and directly neuralizes ectoderm. We further find that (1) Xvents act as transcriptional repressors, (2) Xvents function in an additive fashion and (3) a surprising number of genes are able to rescue dominant-negative Xvent phenotypes including Bmp-4, Smad-1 and wild-type Xvents and Xhox3, but not Xwnt-8. The results show that Xvent-1 and Xvent-2 are essential for ventral mesoderm formation and for preventing neural differentiation. A model is suggested to explain how Bmp-4 positional information is converted into distinct cellular responses.

Animals↗
PubMed2001

Technical Advance. Tobacco rattle virus as a vector for analysis of gene function by silencing.

Virus vectors carrying host-derived sequence inserts induce silencing of the corresponding genes in infected plants. This virus-induced gene silencing (VIGS) is a manifestation of an RNA-mediated defence mechanism that is related to post-transcriptional gene silencing (PTGS) in transgenic plants. Here we describe an infectious cDNA clone of tobacco rattle virus (TRV) that has been modified to facilitate insertion of non-viral sequence and subsequent infection to plants. We show that this vector mediates VIGS of endogenous genes in the absence of virus-induced symptoms. Unlike other RNA virus vectors that have been used previously for VIGS, the TRV construct is able to target host RNAs in the growing points of plants. These features indicate that the TRV vector will have wide application for gene discovery in plants.

Base Sequence↗
PubMed2000

A single-transformation gene function test in diploid Candida albicans.

The fungal pathogen Candida albicans is naturally diploid, and current gene disruption strategies require two successive transformations. We describe here a genetic construct (UAU1) for which two copies may be selected. Insertion of UAU1 into one genomic site, after a single transformation, allows selection for segregants with two copies of the insertion. Major classes of segregants are those carrying homozygous insertion mutations and allelic triplications, which have two insertion alleles and a wild-type allele. Thus nonessential and essential genes may be distinguished rapidly through PCR tests for homozygosis and triplication. We find that homozygous mutations may be isolated at three nonessential loci (ADE2, RIM20, and YGR189), while only allelic triplications were found at two essential loci (SNF1 and CDC28). We have unexpectedly isolated homozygous mutants with mutations at CDC25; they are viable but defective in filamentation on serum-containing medium. The UAU1 cassette is thus useful to assess rapidly the essentiality of C. albicans genes.

Base Sequence↗
PubMed2006

Effects of low-shear modeled microgravity on cell function, gene expression, and phenotype in Saccharomyces cerevisiae.

Only limited information is available concerning the effects of low-shear modeled microgravity (LSMMG) on cell function and morphology. We examined the behavior of Saccharomyces cerevisiae grown in a high-aspect-ratio vessel, which simulates the low-shear and microgravity conditions encountered in spaceflight. With the exception of a shortened lag phase (90 min less than controls; P < 0.05), yeast cells grown under LSMMG conditions did not differ in growth rate, size, shape, or viability from the controls but did differ in the establishment of polarity as exhibited by aberrant (random) budding compared to the usual bipolar pattern of controls. The aberrant budding was accompanied by an increased tendency of cells to clump, as indicated by aggregates containing five or more cells. We also found significant changes (greater than or equal to twofold) in the expression of genes associated with the establishment of polarity (BUD5), bipolar budding (RAX1, RAX2, and BUD25), and cell separation (DSE1, DSE2, and EGT2). Thus, low-shear environments may significantly alter yeast gene expression and phenotype as well as evolutionary conserved cellular functions such as polarization. The results provide a paradigm for understanding polarity-dependent cell responses to microgravity ranging from pathogenesis in fungi to the immune response in mammals.

Biomechanical Phenomena↗
PubMed1994

Selected Aspects of Homeobox Gene Function during Mammalian Development.

The genetic pathways of development are only beginning to be revealed. But the tools now exist to allow the rapid isolation of genes that carry sequence motifs such as the homeobox, zinc finger or basic-helix loop helix that can mark genes of special developmental significance. Expression patterns are readily determined by in situ hybridization and in vivo developmental functions can be analyzed by generating mice with targeted mutations. Upstream regulators of genes can be identified by finding proteins that bind to cis-regulatory elements. Downstream targets are more difficult to find but there are polymerase chain reaction approaches to define sequences bound by transcription factors and subtractive library approaches to finding specific targets. Although an enormous amount of work remains to be done it is clear that the basic techniques necessary to understand the genetic program of mammalian development are now available. As these techniques are applied and refined we will elaborate the genetic regulatory pathways of organogenesis. This will be deeply satisfying from an intellectual perspective. It will also lead to a better understanding of birth defects and to better treatments of a variety of diseases that involve organ malformation or deterioration. Copyright 1994 S. Karger AG, Basel

Journal Article↗