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At least 253 records · Page 14Linked to original sources
PubMed1996

Expression of the recombinase-activating gene (RAG-1) in murine early embryogenesis.

The recombinase activation genes, RAG-1 and RAG-2, are expressed together in immature T or B lymphocytes and possess activity to induce V(D)J rearrangement in T cell receptor (TCR) and Ig genes. In vertebrates, only Ig and TCR molecules are reported to have recombination in their development using multiple V, D, J component gene segments. Thus, expression of RAG genes are localized only in lymphoid organs and sites of extrathymic T cell differentiation. In this study, we have used RAG-1 and RAG-2 genes as markers of possible genetic recombination in developing murine preimplantation embryos, using the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) technique and in situ hybridization. From 40 preimplantation embryos of various developmental stages we extracted RNA, reverse-transcribed it into cDNA and used it in RT-PCR studies. A PCR of 35 cycles disclosed expression of RAG-1 but not RAG-2 in morulae and blastocysts. Southern blot hybridization using a specific synthetic oligonucleotide probe for RAG-1 and RT-PCR with another primer pair identified RAG-1 expression in developing embryos. In situ hybridization using a cooled CCD camera also revealed localization of RAG-1 mRNA in blastocysts. We propose possible genetic recombination during late preimplantation murine embryogenesis which may contribute to the loss of totipotency and differentiation of inner cell mass and trophoectoderm.

Animals↗
PubMed1996

Insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and dead eye, essential for embryonic development.

Recently our laboratory described an efficient method for generating retroviral provirus insertions in the zebrafish germ line, and we showed that provirus insertions induce embryonic mutations at a frequency of roughly one mutant per 70 insertions. To date we have isolated four insertional mutants and, using the proviruses as a molecular tag, have cloned the genes disrupted in three of them. The proviruses in all three mutants lie within or just 5' of the first coding exon, point in the opposite transcriptional orientation from the gene, and disrupt transcription. Here we present a molecular characterization of two genes identified by this method and describe the associated mutant phenotypes. The pescadillo (pes) gene is predicted to encode a protein of 582 amino acids with no recognizable functional motifs, which is highly conserved from yeast to humans. pes mRNA is expressed widely and dynamically during the first 3 days of embryogenesis. Prominent sites of expression are the eyes and optic tectum on day 1, the fin buds, liver primordium, and gut on day 2, and the branchial arches on day 3. Beginning at day 3 of embryogenesis, pes mutant embryos exhibit small eyes, a reduced brain and visceral skeleton, shortened fins, and a lack of expansion of the liver and gut, and then die on the sixth day of development. The dead eye (dye) gene encodes a protein of 820 amino acids that is homologous to genes of unknown function in human, mouse, and Xenopus, and that has weak homology with the yeast NIC96 (nucleoporin-interacting component) gene. dye mutants can be recognized on day 2 of embryogenesis by the presence of necrotic cells in the tectum and eyes. dye mutants die on day 5 of development. These results demonstrate the power of insertional mutagenesis in zebrafish for rapidly finding and characterizing novel genes essential for embryonic development. Using our current methodology, we estimate that our laboratory could screen approximately 25,000 insertions in 2-3 years, identifying perhaps 250-350 embryonic lethal genes. Assuming that all genes are accessible to proviral insertion, the wider application of this approach could lead to the rapid identification of the majority of genes that are required for embryonic development of this vertebrate.

Amino Acid Sequence↗
PubMed2006

The HOX genes are expressed, in vivo, in human tooth germs: in vitro cAMP exposure of dental pulp cells results in parallel HOX network activation and neuronal differentiation.

Homeobox-containing genes play a crucial role in odontogenesis. After the detection of Dlx and Msx genes in overlapping domains along maxillary and mandibular processes, a homeobox odontogenic code has been proposed to explain the interaction between different homeobox genes during dental lamina patterning. No role has so far been assigned to the Hox gene network in the homeobox odontogenic code due to studies on specific Hox genes and evolutionary considerations. Despite its involvement in early patterning during embryonal development, the HOX gene network, the most repeat-poor regions of the human genome, controls the phenotype identity of adult eukaryotic cells. Here, according to our results, the HOX gene network appears to be active in human tooth germs between 18 and 24 weeks of development. The immunohistochemical localization of specific HOX proteins mostly concerns the epithelial tooth germ compartment. Furthermore, only a few genes of the network are active in embryonal retromolar tissues, as well as in ectomesenchymal dental pulp cells (DPC) grown in vitro from adult human molar. Exposure of DPCs to cAMP induces the expression of from three to nine total HOX genes of the network in parallel with phenotype modifications with traits of neuronal differentiation. Our observations suggest that: (i) by combining its component genes, the HOX gene network determines the phenotype identity of epithelial and ectomesenchymal cells interacting in the generation of human tooth germ; (ii) cAMP treatment activates the HOX network and induces, in parallel, a neuronal-like phenotype in human primary ectomesenchymal dental pulp cells.

Adolescent↗
PubMed2001

Psychrotolerant species from the Bacillus cereus group are not necessarily Bacillus weihenstephanensis.

Twenty-six strains of Bacillus cereus from different sources were determined to be either mesophilic or psychrotrophic by growth at 6 and 42 degrees C. The strains were also screened by two polymerase chain reaction (PCR) methods designed to discriminate between mesophilic and psychrotrophic types. Seventeen of the 26 strains were able to grow at 6 degrees C, but only four conformed to the new psychrotolerant species Bacillus weihenstephanensis. Among the 26 strains were two which caused outbreaks of food poisoning in Norway, and three others that were isolated from food suspected of causing illness. The presence of the gene components encoding production of enterotoxins Nhe, Hbl, EntT and a recently described cytotoxin K was determined by PCR. All the strains possessed genes for at least one of these toxins, and 19 of the 26 strains were cytotoxic in a Vero cell assay. We conclude that there are psychrotrophic B. cereus strains which cannot be classified as B. weihenstephanensis, and that intermediate forms between the two species exist. No correlation between cytotoxicity and the growth temperature of the strains was found.

Animals↗
PubMed1995

[Disappearance of ALS from Guam: implications for exogenous causes].

The author reports the disappearance of amyotrophic lateral sclerosis (ALS) from Guam over past 30 years, which coincided with rapid changes in the ecology, socioeconomy, and westernization of the life style. This slow but steady decline is believed to be the consequences of radical changes from food collection to wage-based life style and dietary improvement in recent years and elimination of exogenous factors. Those risk factor(s) are believed to be the environmental trace metals which must have triggered the accelerated oxidative stresses in the motor neurons of genetically susceptible population. Changing Epidermiology: 1. The annual incidence of 70/100,000 in 1960s down to 7/100,000 in 1990s, and remained unchanged for past 15 years. 2. Upward shift of age at onset by 10 years and at death by 8 years and even out of sex ratio. 3. Birth cohort analysis showed less risks for those born after 1920. No ALS cases born after 1945. 4. No increase in the incidence of ALS among non-Chamorros transients of Guam and Marianas during W.W.II. 5. Long-term resident non-Charmorro and half-Chamorros on Guam are also affected. 6. Charmorro migrants to U.S. Mainland are affected after long absence from Guam. 7. Incubation period for both ways is estimated to be 18 approximately 20 years. 8. Other forms of dementias like Alzheimer disease (AD) and vascular dementias are on the rise and the leading cause of death is cerebro- and cardiovascular diseases. 9. ALS is also declining in past 10 approximately 15 years in Kii peninsula, and West New Guinea. Changing Ecology of Guam: 1. One third of Island land was used for construction of huge military bases after W.W.II. 2. Urbanization of villages including concrete houses, deep well water supply, sewage, and electrification. 3. Tourism boom: high-rise hotels, development of 7 golf courses and other recreational facilities resulted in loss of flora and erosions of soil. Socioeconomic Changes: 1. Shift in population demography; Efflux of Chamorros and influx of aliens; Chamorros less than 50% by 1990. 2. Tourists passed 1 million in 1994. 3. Automobiles 1 car/1.5 person. 4. Westernization: After W.W.II, almost free access to Military Commissary for imported food and appliances. 5. Life style: from food collection to wage-based society. Genetic Studies: 1. Familial aggregations, but no clear-cut Mendelian inheritance. 2. Segregation analysis: no absolute genetic or environmental cause but additive gene component may play a role in genetic susceptibility and basis for geographical clustering. 3. Absence of Apo-E or Mu/Zn SOD genes. 4. Recent discovery of mtDNA Complex I deficiency in Parkinsonism-dementia cases suggests mitochondrial DNA abnormality. Comparative Environmental Studies: 1. Environmental studies in three hyperendemic areas in the Western Pacific--Kii, Marianas, and west New Guinea, where strikingly high incidences of ALS is known to occur, found the identical geochemical environment--low Ca, Mg, and Zn and high A1, Mn, Fe, Si, in the garden soil and drinking water. 2. Exogenous etiologic factors that are absent from primitive culture of Auyu and Jackai tribes in West New Guinea were eliminated. 3. Cycad neurotoxicity has been excluded. 4. Suspected exogenous agents that are common in these 3 hyperendemic areas are (a) locally grown vegetables, starchy roots, and reef fish; (b) surface water containing soluble organic minerals from red laterites; (c) rain water that is chemically pure and lack of essential minerals. Pathogenic Speculation: Chronic dietary deficiency since birth in Ca, Mg and Zn induced excessive absorption of divalent cations which accelerates oxidant-mediated neuronal degenerations in a genetically susceptible population. The process is probably carried through interactions between cytoskeletal abnormality of the neuron, aging process, abnormal proteins, and mitochondrial dysfunction.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

Complexity in the major histocompatibility complex.

The human major histocompatibility complex (MHC) is one of the most intensively studied regions of the human genome, containing over 70 known genes and spanning about 4 million base pairs (4 Mbp) of DNA on chromosome 6p21.3 (Klein, 1986). It can be divided up into three regions: the class I region (telomeric), the class II region (centromeric), and the class III region (between class I and II), which includes the complement component genes C2, C4, and Bf (Trowsdale & Campbell, 1988). The MHC has been mapped in detail using pulse field gel electrophoresis (PFGE) and by cloning in yeast artificial chromosome (YAC) and cosmid vectors, revealing long stretches of DNA between the regions as well as between individual class I and class II genes. Novel genes, that have no sequence relationships with class I, class II or complement components, have recently been found in these areas, and we will present an update on these after reviewing the more established loci.

Chromosome Mapping↗
PubMed2006

Role of defense/stress-related marker genes, proteins and secondary metabolites in defining rice self-defense mechanisms.

Rice, a first cereal crop whose draft genome sequence from two subspecies (japonica-type cv. Nipponbare and indica-type 93-11) was available in 2002, along with its almost complete genome sequence in 2005, has drawn the attention of researchers worldwide because of its immense impact on human existence. One of the most critical research areas in rice is to discern the self-defense mechanism(s), an innate property of all living organisms. The last few decades have seen scattered research into rice responses to diverse environmental stimuli and stress factors. Our understanding on rice self-defense mechanism has increased considerably with accelerated research during recent years mainly due to identification and characterization of several defense/stress-related components, genes, proteins and secondary metabolites. As these identified components have been used to study the defense/stress pathways, their compilation in this review will undoubtedly help rice (and others) researchers to effectively use them as a potential marker for better understanding, and ultimately, in defining rice (and plant) self-defense response pathways.

Gene Expression Regulation, Plant↗
PubMed2005

Balancing selection and low recombination affect diversity near the self-incompatibility loci of the plant Arabidopsis lyrata.

The self-incompatibility (S-) locus region of plants in the Brassica family is a small genome region. In Arabidopsis lyrata, the S-genes, SRK and SCR, encode the functional female and pollen recognition proteins, which must be coadapted to maintain correct associations between the two component genes, and thus self-incompatibility (SI). Recombinants would be self-compatible and thus probably disadvantageous in self-incompatible species. Therefore, tight linkage between the two genes in incompatibility systems is predicted to evolve to avoid producing such recombinant haplotypes. The evolution of low recombination in S-locus regions has not been rigorously tested. To test whether these regions' per-nucleotide recombination rates differ from those elsewhere in the genome, and to investigate whether the A. lyrata S-loci have the predicted effect on diversity in their immediate genome region, we studied diversity in genes that are linked to the S-loci but are not involved in incompatibility and are not under balancing selection. Compared with other A. lyrata loci, genes linked to the S-loci have extraordinarily high polymorphism. Our estimated recombination in this region, from fitting a model of the effects of S-allele polymorphism on linked neutral sites, supports the hypothesis of locally suppressed recombination around the S-locus.

Arabidopsis↗
PubMed1992

Characterization of the DNA-binding activity of GCR1: in vivo evidence for two GCR1-binding sites in the upstream activating sequence of TPI of Saccharomyces cerevisiae.

GCR1 gene function is required for high-level glycolytic gene expression in Saccharomyces cerevisiae. Recently, we suggested that the CTTCC sequence motif found in front of many genes encoding glycolytic enzymes lay at the core of the GCR1-binding site. Here we mapped the DNA-binding domain of GCR1 to the carboxy-terminal 154 amino acids of the polypeptide. DNase I protection studies showed that a hybrid MBP-GCR1 fusion protein protected a region of the upstream activating sequence of TPI (UASTPI), which harbored the CTTCC sequence motif, and suggested that the fusion protein might also interact with a region of the UAS that contained the related sequence CATCC. A series of in vivo G methylation protection experiments of the native TPI promoter were carried out with wild-type and gcr1 deletion mutant strains. The G doublets that correspond to the C doublets in each site were protected in the wild-type strain but not in the gcr1 mutant strain. These data demonstrate that the UAS of TPI contains two GCR1-binding sites which are occupied in vivo. Furthermore, adjacent RAP1/GRF1/TUF- and REB1/GRF2/QBP/Y-binding sites in UASTPI were occupied in the backgrounds of both strains. In addition, DNA band-shift assays were used to show that the MBP-GCR1 fusion protein was able to form nucleoprotein complexes with oligonucleotides that contained CTTCC sequence elements found in front of other glycolytic genes, namely, PGK, ENO1, PYK, and ADH1, all of which are dependent on GCR1 gene function for full expression. However, we were unable to detect specific interactions with CTTCC sequence elements found in front of the translational component genes TEF1, TEF2, and CRY1. Taken together, these experiments have allowed us to propose a consensus GCR1-binding site which is 5'-(T/A)N(T/C)N(G/A)NC(T/A)TCC(T/A)N(T/A)(T/A)(T/G)-3'.

Base Sequence↗
PubMed2006

A nuclear receptor corepressor-dependent pathway mediates suppression of cytokine-induced C-reactive protein gene expression by liver X receptor.

C-reactive protein (CRP), the prototypical human acute phase protein, is an independent risk predictor of future cardiovascular events, both in healthy individuals and in patients with known cardiovascular disease. In addition, previous studies indicate that CRP might have direct proatherogenic properties. Ligand activation of the liver X receptor (LXR), a member of the nuclear hormone receptor superfamily, inhibits inflammatory gene expression in macrophages and attenuates the development of atherosclerosis in various animal models. We demonstrate herein that 2 synthetic LXR ligands, T0901317 and GW3965, inhibit interleukin-1beta/interleukin-6-induced CRP mRNA and protein expression in human hepatocytes. Knockdown of LXRalpha/beta by short interfering RNAs completely abolished the inhibitory effect of the LXR agonist T0901317 on cytokine-induced CRP gene transcription. Transient transfection experiments with 5'-deletion CRP promoter constructs identified a region from -125 to -256 relative to the initiation site that mediated the inhibitory effect of LXR ligands on CRP gene transcription. Depletion of the nuclear receptor corepressor by specific short interfering RNA increased cytokine-inducible CRP mRNA expression and promoter activity and reversed LXR ligand-mediated repression of CRP gene transcription. Chromatin immunoprecipitation assays indicated that nuclear receptor corepressor is present on the endogenous CRP promoter under basal conditions. Cytokine-induced clearance of nuclear receptor corepressor complexes was inhibited by LXR ligand treatment, maintaining the CRP gene in a repressed state. Finally, treatment of C57Bl6/J mice with LXR ligands attenuated lipopolysaccharide-induced mouse CRP and serum amyloid P component gene expression in the liver, whereas no effect was observed in LXRalphabeta knockout mice. Our observations identify a novel mechanism of inflammatory gene regulation by LXR ligands. Thus, inhibition of CRP expression by LXR agonists may provide a promising approach to impact initiation and progression of atherosclerosis.

Acute-Phase Reaction↗
PubMed2006

Regulatable gene expression systems for gene therapy.

It is feasible to restrict transgene expression to a tissue or region in need of therapy by using promoters that respond to focusable physical stimuli. The most extensively investigated promoters of this type are radiation-inducible promoters and heat shock protein gene promoters that can be activated by directed, transient heat. Temporal regulation of transgenes can be achieved by various two- or three-component gene switches that are triggered by an appropriate small molecule inducer. The most commonly considered gene switches that are reviewed herein are based on small molecule-responsive transactivators derived from bacterial tetracycline repressor, insect or mammalian steroid receptors, or mammalian FKBP12/FRAP. A new generation of gene switches combines a heat shock protein gene promoter and a small molecule-responsive gene switch and can provide for both spatial and temporal regulation of transgene activity.

Animals↗
PubMedDate not supplied

Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction.

BACKGROUND CONTEXT: Serial analysis of gene expression during the course of intervertebral disc degeneration (IDD) could elucidate valuable insight into pathophysiology and provide a basis for identification of potential targets for the development of novel cellular- and gene-based therapies. However, very few previous studies described the changes in gene expression through the process of IDD using a suitable animal model. PURPOSE: To use a recently developed rabbit annular stab model and the technique of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify the change in expression of key rabbit-specific mRNA sequences encoding for selected extracellular matrix (ECM) products, catabolic, anabolic, and anti-catabolic factors in normal and stabbed discs. STUDY DESIGN: Gene expression analyses were performed to characterize a slowly progressive and reproducible animal model of IDD using real-time RT-PCR. METHODS: Twelve rabbits underwent an annular stab with a 16-gauge needle to the L2-L3, L3-L4, and L4-L5 discs, and three rabbits served as sham controls. Nucleus pulposus tissues were harvested from the stabbed discs at 3, 6, 12 and 24 weeks after confirmation of degenerative changes by magnetic resonance imaging (MRI) scan. Real-time RT-PCR was performed with the use of rabbit-specific primers for 1) extracellular matrix (ECM) component genes: collagen type Ia and IIa, and aggrecan; 2) catabolic genes: matrix metalloprotease-3 (MMP-3), inducible nitric oxide synthase (iNOS), and interleukin-1beta (IL-1beta); 3) anabolic growth genes: bone morphogenic protein-2, and -7 (BMP-2, -7), transforming growth factor-beta1 (TGF-beta1), and insulin-like growth factor-1 (IGF-1); and 4) anti-catabolic gene: tissue inhibitor of metalloprotease-1 (TIMP-1). These data were normalized to mRNA levels of glyceraldehyde phosphate dehydrogenase (GAPDH), a constitutively expressed gene. RESULTS: The MRI images confirmed progressive decline in the nucleus pulposus area of high T2 signal and in the signal intensity of the stabbed discs over the 24-week study period consistent with IDD. The ECM components, aggrecan and collagen type IIa mRNA levels had decreased markedly by week 3 and never recovered, whereas type Ia collagen mRNA gradually increased throughout course of degeneration. BMP-2, BMP-7 and IGF-1 mRNA were relatively decreased from weeks 3 to 6 but then increased at weeks 12 and 24 to end at a level near the preoperative level. The TIMP-1 expression fell dramatically to approximately one tenth of the preoperative level by week 3 and remained low throughout the degenerative process. The remaining results, including those from TGF-beta1 and the catabolic genes (MMP-3, IL-1beta, iNOS) demonstrated a double peak characteristic. The gene expression increased by week 3, decreased to a low level at weeks 6 and 12 and then had a second, late peak at 24 weeks. CONCLUSIONS: The gene expression profiles of ECM components and anabolic, catabolic, and anti-catabolic factors demonstrate many characteristics similar to the findings in human disc degeneration and suggest an inability of the intervertebral disc (IVD) to mount an early anabolic response to injury, thereby offering a possible explanation for the disc's lack of reparative capabilities. Catabolic genes are strongly up-regulated both early and late in degeneration, lending strong support to the hypothesis that an anabolic or catabolic imbalance plays a primary role in IDD. According to the resultant patterns, augmenting early production of BMP-2, BMP-7, IGF-1 or TIMP-1 by gene transfer techniques might possibly alter the progressive course of degeneration as seen in the stab model. The next step will be to transfer these therapeutic genes to regulate the biologic processes and ideally alter the progressive course of disc degeneration.

Animals↗
PubMed2006

Hath1 up-regulates gastric mucin gene expression in gastric cells.

The Notch signaling pathway is known to mediate the differentiation and fate specification of cells in embryonic stage and adult tissues. Several tumors exhibit aberrant expression of Notch signaling component genes, such as Notch1/2/3 and Hath1. In this study, we investigated the mRNA expression of seven Notch-related genes, Notch1/2/3, Hes1/2/3, and Hath1, and then compared it with the expression of gastric mucin genes, MUC5AC and MUC6, in eight gastric cancer (GC) cell lines. Notch1/2/3 and Hes1 were expressed in most GC cell lines as well as normal gastric mucosae, while Hes2/3 were expressed in neither these cell lines nor the normal stomach. As for Hath1, five GC cell lines exhibited undetectable levels, while normal gastric mucosa expressed Hath1. The expression patterns of Hath1 and MUC6 were closely related in most GC cell lines. Many MUC5AC-positive cases also tended to show Hath1 expression. Over-expression of Math1, a mouse Hath1 homolog, in the GC cells strongly enhanced both the MUC6 and MUC5AC mRNA levels. Moreover, knockdown of Hath1 by means of RNA interference significantly decreased the expression of both mucin genes. These data indicate that Hath1 is one of the transcriptional regulators for MUC6 and MUC5AC in GC cells. It is also possible that loss of Hath1 expression may play a role in gastric carcinogenesis.

Animals↗
PubMedDate not supplied

Molecular regulation of cell-cycle progression and apoptosis in mammalian cells: implications for biotechnology.

Regulation of the cell cycle and of programmed cell death (apoptosis) is essential for mammalian development and homeostasis. Furthermore, this regulation is fundamental to successful cell culture technology and tissue engineering. Therefore the molecular networks which regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. This review summarizes the genes, proteins, and interactions presently known to control apoptosis and cell-cycle progression. Knowledge of the networks summarized here and access to the component genes and proteins have already been applied successfully to guide research and development in bioprocess technology and medical treatment.

Animals↗
PubMed1989

Genetical variation and polyphyletic origin in Japanese Mus musculus.

Previous reports of mitochondrial DNA variation in Japanese mice have revealed the occurrence of two components, a M. m. musculus mtDNA type in central Japan and a M. m. castaneus one at both northern and southern ends. In the present study, we explore the genetic composition of nuclear genes from Japanese wild mice. Protein electrophoresis at 16 polymorphic loci was used to characterise mice from 20 localities and to compare them with samples from the surrounding countries. The results revealed a predominant M. m. musculus nuclear gene component on the main Japanese Islands. A M. m. castaneus contribution was detectable in south Kyushu, but, interestingly, not evident in Northern Honshu were the castaneus mtDNA predominates. On the other hand, the mouse populations from Ogasawara (Chichi Islands) showed a threefold origin with a strong M. m. domesticus component, probably resulting from a very recent admixture. This clearcut example of reticulate evolution, which does not give rise to an homogeneous gene distribution, is however very different from the situation observed in the European hybrid zone. This raises questions concerning the mechanisms that either impede or favour gene admixture when differentiated gene pools are brought together.

Alleles↗
PubMed1981

Transcriptional and post-transcriptional control of ribosomal protein and ribonucleic acid polymerase genes.

A partial restriction of ribonucleic acid (RNA) polymerase activity has been used to dissociate the coordinate synthesis of ribosomal proteins and subunits of RNA polymerase and to identify transcriptional and post-transcriptional control signals which regulate the expression of these component genes. Within the beta operon [which has the genetic organization: promoter (p beta), rplJ (L10), r;lL (L7/L12), attenuator, rpoB (beta), rpoC (beta'), terminator], the restriction caused a disproportionate increase between proximal and distal gene transcriptions; the transcriptional intensities of the proximal ribosomal protein genes and the distal RNA polymerase genes were elevated about two- and fourfold, respectively. Transcription within the operon containing four ribosomal protein genes and the RNA polymerase alpha gene was also enhanced, whereas transcription within operons containing only ribosomal protein genes was virtually unaffected by the restriction. It was thus concluded that the mechanisms controlling transcription initiation or attenuation or both in operons containing RNA polymerase subunit genes are coupled to the global rate of RNA synthesis. By introducing the composite ColE1 plasmid pJC701 carrying the proximal portion of the L10 operon, including the beta subunit gene, it was possible to achieve a 10- and a 30-fold range in the transcriptional intensities of the genes specifying L10 and L7/L12 and beta, respectively. Under these conditions, the relative synthesis rates of L7/L12 and beta protein varied by less than 2-fold and by about 15-fold, respectively. These observations corroborate the existence of a post-transcriptional mechanism which severely restricts translation of excess L7/L12 and L10 ribosomal protein messenger RNA; this mechanism is probably important in maintaining the balanced synthesis of ribosome components under conditions in which their messenger RNA levels are dissociated. Furthermore, the observed reduction in the translation efficiency of beta subunit messenger RNA may be related to an inhibitory effect caused by accumulation of RNA polymerase assembly intermediates.

Bacterial Proteins↗
PubMed2002

Partial least squares proportional hazard regression for application to DNA microarray survival data.

MOTIVATION: Microarrays are increasingly used in cancer research. When gene transcription data from microarray experiments also contains patient survival information, it is often of interest to predict the survival times based on the gene expression. In this paper we consider the well-known proportional hazard (PH) regression model for survival analysis. Ordinarily, the PH model is used with a few covariates and many observations (subjects). We consider here the case that the number of covariates, p, exceeds the number of samples, N, a setting typical of gene expression data from DNA microarrays. RESULTS: For a given vector of response values which are survival times and p gene expressions (covariates) we examine the problem of how to predict the survival probabilities, when N << p. The approach taken to cope with the high dimensionality is to reduce the dimension using partial least squares with the response variable as the vector of survival times. After dimension reduction, the extracted PLS gene components are then used as covariates in a PH regression to predict the survival probabilities. We demonstrate the use of the methodology on two cDNA gene expression data sets, both containing survival data. The first data set contains 40 diffuse large B-cell lymphoma (DLBCL) tissue samples and the second data set contains 49 tissue samples from patients with locally advanced breast cancer in a prospective study.

Breast Neoplasms↗
PubMed1984

Genetic study of an orthopedic referral center.

A prospective study of patients seen at the Shriners Hospital for Crippled Children, Houston Unit, showed that there is a substantial genetic component to orthopedic disorders. A mean of 25% of new patients and 46% of specialty clinic patients had orthopedic diseases of genetic etiology. The respective single gene component was 7.2% and 12.9%. Rare disorders were observed, and some of these are discussed. The results indicate that genetic counseling should be an integral part of orthopedic care.

Adolescent↗