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At least 649 records · Page 36Linked to original sources
PubMed2006

Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse.

Regulatory changes in genes involved in reproduction are thought to be prime targets for divergence during speciation, since they are expected to play an important role in sexual selection and sexual conflict. We used microarray analysis of RNA from different wild populations of house mouse subspecies (including Mus m. musculus, Mus m. domesticus, and Mus m. castaneus) and from the sister species Mus spretus to test this assumption. A comparison of expression divergence in brain, liver/kidney, and testis shows a major difference in the evolutionary dynamics of testis-related genes. While the comparison between species confirms an excess in divergence in testis genes, we find that all comparisons between subspecies yield only a very small number of genes with significantly different expression levels in the testis. These results suggest that the early phase of the speciation process may not be driven by regulatory changes in genes that are potential targets of sexual selection, and that the divergence in these genes is only established during a later phase of the speciation process.

Animals↗
PubMed2004

The homogentisate pathway: a central catabolic pathway involved in the degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in Pseudomonas putida.

Pseudomonas putida metabolizes Phe and Tyr through a peripheral pathway involving hydroxylation of Phe to Tyr (PhhAB), conversion of Tyr into 4-hydroxyphenylpyruvate (TyrB), and formation of homogentisate (Hpd) as the central intermediate. Homogentisate is then catabolized by a central catabolic pathway that involves three enzymes, homogentisate dioxygenase (HmgA), fumarylacetoacetate hydrolase (HmgB), and maleylacetoacetate isomerase (HmgC), finally yielding fumarate and acetoacetate. Whereas the phh, tyr, and hpd genes are not linked in the P. putida genome, the hmgABC genes appear to form a single transcriptional unit. Gel retardation assays and lacZ translational fusion experiments have shown that hmgR encodes a specific repressor that controls the inducible expression of the divergently transcribed hmgABC catabolic genes, and homogentisate is the inducer molecule. Footprinting analysis revealed that HmgR protects a region in the Phmg promoter that spans a 17-bp palindromic motif and an external direct repetition from position -16 to position 29 with respect to the transcription start site. The HmgR protein is thus the first IclR-type regulator that acts as a repressor of an aromatic catabolic pathway. We engineered a broad-host-range mobilizable catabolic cassette harboring the hmgABC, hpd, and tyrB genes that allows heterologous bacteria to use Tyr as a unique carbon and energy source. Remarkably, we show here that the catabolism of 3-hydroxyphenylacetate in P. putida U funnels also into the homogentisate central pathway, revealing that the hmg cluster is a key catabolic trait for biodegradation of a small number of aromatic compounds.

Bacterial Proteins↗
PubMed2003

Epigenetic phenomena and the evolution of plant allopolyploids.

Allopolyploid speciation is widespread in plants, yet the molecular requirements for successful orchestration of coordinated gene expression for two divergent and reunited genomes are poorly understood. Recent studies in several plant systems have revealed that allopolyploid genesis under both synthetic and natural conditions often is accompanied by rapid and sometimes evolutionarily conserved epigenetic changes, including alteration in cytosine methylation patterns, rapid silencing in ribosomal RNA and protein-coding genes, and de-repression of dormant transposable elements. These changes are inter-related and likely arise from chromatin remodeling and its effects on epigenetic codes during and subsequent to allopolyploid formation. Epigenetic modifications could produce adaptive epimutations and novel phenotypes, some of which may be evolutionarily stable for millions of years, thereby representing a vast reservoir of latent variation that may be episodically released and made visible to selection. This epigenetic variation may contribute to several important attributes of allopolyploidy, including functional diversification or subfunctionalization of duplicated genes, genetic and cytological diploidization, and quenching of incompatible inter-genomic interactions that are characteristic of allopolyploids. It is likely that the evolutionary success of allopolyploidy is in part attributable to epigenetic phenomena that we are only just beginning to understand.

Biological Evolution↗
PubMed2005

The molecular genetics of gastroenteropancreatic neuroendocrine tumors.

The pathobiology of neuroendocrine tumors (NETs) is hampered by the lack of scientific tools that define their mechanisms of secretion, proliferation, and metastasis; and, currently, there are no accurate means to assess tumor behavior and disease prognosis. Molecular biologic techniques and genetic analysis may facilitate the delineation of the molecular pathology of NETs and provide novel insights into their cellular mechanisms. The current status and recent advances in assessment of the molecular basis of tumorigenesis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) were reviewed (1981-2004). The objectives of this retrospective study were to provide a cohesive overview of the current state of knowledge and to develop a molecular understanding of these rare tumor entities to facilitate the establishment of therapeutic targets and rational management strategies. Multiple differences in chromosomal aberration patterns were noted between gastrointestinal (GI) neuroendocrine and pancreatic endocrine tumors (PETs). Divergence in gene expression patterns in the development of GI carcinoids and PETs was identified, whereas examination of the PET and GI carcinoid data demonstrated only few areas of overlap in the accumulation of genetic aberrations. These data suggest that the recent World Health Organization classification of GEP-NETs may require updating. In addition, previous assumptions of tumor similarity (pancreatic vs. GI) may be unfounded when they are examined at a molecular level. On the basis of the evolution of genetic information, enteric neuroendocrine lesions (carcinoids) and PETs may need to be classified as two distinct entities rather than grouped together as the single entity "GEP-NETs."

Carcinoid Tumor↗
PubMed2002

Distribution of two splice variants of the glutamate transporter GLT1 in the retinas of humans, monkeys, rabbits, rats, cats, and chickens.

Antibodies have been generated against two carboxyl-terminal splice variants of the glutamate transporter GLT1, namely, the originally described version of GLT1 and GLT1-B, and labelling has been examined in multiple species, including chickens and humans. Although strong specific labelling was observed in each species, divergent patterns of expression were noted. Moreover, each antibody was sensitive to the phosphorylation state of the appropriate protein, because chemical removal of phosphates using alkaline phosphatase revealed a broader range of labelled elements in most cases. In general, GLT1-B was present in cone photoreceptors and in rod and cone bipolar cells in the retinas of rabbits, rats, and cats. In the cone-dominated retinas of chickens and in marmosets, GLT1-B was associated only with cone photoreceptors, whereas, in macaque and human retinas, GLT1-B was associated with bipolar cells and terminals of photoreceptors. In some species, such as cats, GLT-B was also present in horizontal cells. By contrast, GLT1 distribution varied. GLT1 was associated with amacrine cells in chickens, rats, cats, and rabbits and with bipolar cells in marmosets and macaques. In the rat retina, rod photoreceptor terminals also contained GLT1, but this was evident only in enzymatically dephosphorylated tissues. We conclude that the two variants of GLT1 are present in all species examined but are differentially distributed in a species-specific manner. Moreover, each cell type generally expresses only one splice variant of GLT1.

Amacrine Cells↗
PubMed2000

Functional characterization of the enhancer blocking element of the sea urchin early histone gene cluster reveals insulator properties and three essential cis-acting sequences.

Insulator elements can be functionally identified by their ability to shield promoters from regulators in a position-dependent manner or their ability to protect adjacent transgenes from position effects. We have previously reported the identification of a 265 bp sns DNA fragment at the 3' end of the sea urchin H2A early histone gene that blocked expression of a reporter gene in transgenic embryos when placed between the enhancer and the promoter. Here we show that sns interferes with enhancer-promoter interaction in a directional manner. When sns is placed between the H2A modulator and the inducible tet operator, the modulator is barred from interaction with the basal promoter. However, the tet activator (tTA) can still activate the promoter, even in the presence of sns, demonstrating that sns does not interfere with activity of a downstream enhancer. In addition, the H2A modulator can still drive expression of a divergently oriented transcription unit, suggesting that sns does not inhibit binding of transcription factor(s) to the enhancer. To identify cis-acting sequence elements within sns which are responsible for insulator activity, we have performed in vitro DNase I footprinting and EMSA analysis, and in vivo functional assays by microinjection into sea urchin embryos. We have identified three binding sites for protein complexes: a palindrome, a direct repeat, and a C+T sequence that corresponds to seven GAGA motifs on the transcribed strand. Insulator function requires all three cis-acting elements. Based on these results, we conclude that sns displays properties similar to the best characterized insulators and suggest that directional blocking of enhancer-activated transcription by sns depends on the assembly of distinct DNA-protein complexes.

Animals↗
PubMed1985

The programs of protein synthesis accompanying the establishment of alternative phenotypes in Candida albicans.

Under the regime of pH-regulated dimorphism, stationary phase cells of the dimorphic yeast Candida albicans can be induced to form exclusively and synchronously ellipsoidal buds or elongate mycelia at the same temperature and in the same nutrient medium, the sole determinant of phenotype in this case being pH. Employing pH-regulated dimorphism, cells were pulse-labeled with [35S]-methionine during three consecutive intervals encompassing the preevagination period, the period including evagination and phenotypic commitment, and the post-evagination period. Labeled polypeptides were analyzed by 2D-PAGE. Of the 374 polypeptides examined, the majority (237) did not differ significantly in relative incorporation between the three pulse periods and were similar between budding and mycelium-forming populations. Sixty polypeptides were labeled at negligible or relatively low levels during the first pulse period, but at significantly higher levels during the second and third or third pulse periods. All but one were similar between budding and mycelium-forming populations. Seventeen polypeptides were synthesized at relatively high levels during the first pulse period, but at reduced or negligible levels during the second and third or third pulse periods. All but one were similar between budding and mycelium-forming populations. Only two polypeptides were found to be associated exclusively with mycelium-forming cultures, two associated exclusively with budding cultures, and two enriched significantly in budding cultures of wild-type cells. Employing a variant, MD20, which forms buds at both low and high pH, it was demonstrated that only one mycelium-associated polypeptide and only one bud-associated polypeptide are phenotype rather than pH-specific. Limits to this method of phenotype comparison are outlined, and the unusual similarity rather than dissimilarity in the programs of gene expression between the diverging populations considered in terms of phenotypic regulation.

Candida albicans↗
PubMed1990

In vitro divergence of HSV-1 populations propagated in different cell lines.

To investigate how the structure of a virus population is influenced by the particular cell types in which the virus is propagated, laboratory populations of HSV-1 have been serially passaged onto a number of different cell lines, differing either in species or in tissue specificity. After a limited number of in vitro passages, several of the daughter virus populations have diverged in the expression of at least one phenotype, suggesting that different cell types have selected different variants contained in the parental virus population.

Animals↗
PubMed1979

Sexual dimorphism of mouse fetal brain lesions after X-irradiation prior to gonadal differentiation.

Fractionated X-irradiation of gestational days 11-13 in the mouse, with doses between 3 x 1.05 and 3 x 1.33 Gy resulted in rosette-like clusters of primitive ependym-resembling cells dispersed within the cortex walls. Quantification of these abnormalities showed a general prevalence in the female fetuses, especially due to the larger number of rosettes in the females than in the males. It was concluded that X-irradiation acts on sex-specific differentiation steps, which are fully developed at the beginning of the fetal period. As it was recently speculated that these are linked to an early divergence of gene expression between the sexes, we suggest that X-chromosome damage may be involved in the pathogenesis of the dimorphic lesion pattern. While, in principle, this will valid for any fetal tissue, it only becames evident in the forebrain because of the outstanding relationship between cell necrosis and rosette development in this specific organ.

Animals↗
PubMed1999

Purification and characterization of MerR, the regulator of the broad-spectrum mercury resistance genes in Streptomyces lividans 1326.

Streptomyces lividans 1326 carries inducible mercury resistance genes on the chromosome, which are arranged in two divergently transcribed operons. Expression of the genes is negatively regulated by the repressor MerR, which binds in the intercistronic region between the two operons. The merR gene was expressed in E. coli using a T7 RNA polymerase/promoter expression system, and MerR was purified to around 95% homogeneity by ammonium sulfate precipitation, gel filtration and affinity chromatography. Gel filtration showed that the native MerR is a dimer with a molecular mass of 31 kDa. Two DNA binding sites were identified in the intercistronic mer promoter region by footprinting experiments. No evidence for cooperativity in the binding of MerR to the adjacent operator sequences was observed in gel mobility shift assays. The dissociation constants (K(D)) for binding of MerR were: binding site I, 8.5 x 10(-9) M; binding site II, 1.2 x 10(-8) M; and for the complete promoter/operator region 1 x 10(-8) M. The half-life of the MerR-DNA complex was 19.4 min and 18.8 min for binding site I and binding site II, respectively. The K(D) value for binding of mercury(II)chloride to MerR, again determined by mobility shift assay, was 1.1 x 10(-7) M.

Bacterial Proteins↗
PubMed1994

Desmin and neural marker expression in mesothelial cells and mesotheliomas.

The distribution of keratin, vimentin, desmin, muscular actin, S100, specific neuron enolase, and chromogranin was studied by immunoperoxidase staining in mesothelium, malignant mesotheliomas, and pulmonary carcinomas. The mesothelial cells were positive for keratin and vimentin on all smears of pleural and ascitic effusions; most of them were also positive for desmin but rarely for enolase and S100. None was positive for muscular actin. Sixteen malignant mesotheliomas expressed vimentin and keratin; six were also positive for desmin, three for desmin and neural markers, and five for neural markers. In comparison, none of the pulmonary carcinomas was positive for these markers. Mesothelial cells are able to express markers of divergent differentiation. Mesotheliomas also have such markers that are present in other malignant tumors and, in particular, in intra-abdominal desmoplastic small cell tumors with divergent differentiation. This entity and mesotheliomas probably originate from the same cell. Moreover, desmin, found in 56% of malignant mesotheliomas but absent in pulmonary carcinomas, may be useful in the differential diagnosis of these tumors.

Actins↗
PubMed1992

Muscle differentiation.

Recent studies indicate that vertebrate skeletal muscle originates from two distinct populations of muscle precursor cells formed in early embryogenesis. Divergent patterns of expression for the myoD family of myogenic regulatory genes in different vertebrate embryos suggest some functional redundancy amongst the myogenic factors. Initial gene knockout experiments in mice support this view. Systematic mutagenesis has identified a conserved motif in the basic region of these proteins that is necessary for their biological activity. Direct interaction of both MyoD and myogenin with the transcription factor Jun indicates a mechanism for integrating the control of myoblast growth and differentiation.

Animals↗
PubMed2002

Pregnancy associated plasma protein-A: ultrasensitive immunoassay and determination in coronary heart disease.

OBJECTIVES: Markers of myocardial injury have been vital in the assessment of patients with coronary heart disease. Pregnancy associated plasma protein A (PAPP)-A is an insulin-like growth factor (IGF) binding protein (IGFBP)-4 protease and a potential early indicator of unstable angina. We developed an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for PAPP-A and measured serum PAPP-A in patients with biochemical evidence of acute coronary syndrome. DESIGN AND METHODS: Method development was based on pair-wise evaluation of a panel of antibodies and determination of PAPP-A specificity and sensitivity relative to those of a conventional method. Association of PAPP-A with myocardial damage was assessed in serum samples classified based on serum creatine kinase (CK)-MB or cardiac troponin-T levels. RESULTS: Serum PAPP-A was significantly higher in samples with elevated CK-MB or troponin-T than in samples with normal CK-MB (p < 0.001). Marker-association studies showed strong correlation between PAPP-A and troponin-T (r = 0.59, p < 0.001) in a subset of troponin-T positive samples. Indications for both parallel as well as divergence in the expression of PAPP-A and troponin-T was also evident when serial timed samples available from a number of patients were analyzed. CONCLUSIONS: The data are consistent with the conclusion that expression of PAPP-A is enhanced in patients with biochemical evidence of acute coronary syndrome and suggest strongly that demonstration of PAPP-A association with other cardiac markers might be influenced by their relative release dynamics (timing and duration). The availability of the ultrasensitive PAPP-A ELISA should facilitate systematic investigations of PAPP-A expression in this and other pathophysiological conditions that might involve altered expression of the IGF/PAPP-A system.

Adult↗
PubMed2000

Chicken neuropeptide Y receptor Y2: structural and pharmacological differences to mammalian Y2(1).

Here we report the molecular cloning of the chicken (Gallus gallus) neuropeptide Y (NPY) receptor Y2, the first non-mammalian Y2 receptor. It displays 75-80% identity to mammalian Y2 and has a surprisingly divergent cytoplasmic tail. Expression of the receptor protein in a cell line showed that the receptor did not bind the mammalian Y2 selective antagonist BIIE0246. Furthermore, porcine [Leu(31), Pro(34)]NPY, which binds poorly to mammalian Y2, exhibited an unexpectedly high affinity for chicken Y2. In situ hybridisation revealed expression in the hippocampus. Thus, the chicken Y2 receptor exhibits substantial differences with regard to sequence and pharmacological profile in comparison to mammalian Y2 receptors, while the expression pattern in the central nervous system resembles that observed in mammals.

Amino Acid Sequence↗
PubMed2003

Differential stability and fusion activity of Lyssavirus glycoprotein trimers.

The oligomeric structure and the fusion activity of lyssavirus glycoprotein (G) was studied by comparing G from Mokola virus (GMok) and rabies virus (PV strain) (GPV), which are highly divergent lyssaviruses. G expressed at the surface of BSR cells upon either plasmid transfection or virus infection are shown to be mainly trimeric after cross-linking experiments. However, solubilization by a detergent (CHAPS) and analysis in sucrose sedimentation gradient evidenced that GMok trimer is less stable than GPV trimer. A chimeric glycoprotein (G Mok-PV) associating the N-terminal half of GMok to the C-terminal half part of GPV formed trimers with an intermediate stability, indicating that the G C-terminal domain is essential in trimer stability. A cell to cell fusion assay revealed that GMok (and not G Mok-PV) was able to induce fusion at a higher pH (0.5 pH unit) than GPV. Such differences in the oligomeric structure stability and in the fusion activity of lyssavirus glycoproteins may partly account for the previously reported differences of their immunogenic and pathogenic properties.

Animals↗
PubMed1999

Expression of tubulin polyglycylation in Giardia lamblia.

By means of immunofluorescence, immunoelectron microscopy and immunoblotting, we show that polyglycylation, a posttranslational modification of tubulin widely spread among eukaryotes, is present in the diplomonad, Giardia lamblia, a putative ancestral cell possessing a highly developed microtubular cytoskeleton. This modification was recently discovered in the ciliated protist, Paramecium, and was not found in the Euglenozoa, a lineage considered as ancient. We used two monoclonal antibodies (mAbs), TAP 952 and AXO 49, specifically recognizing mono- and polyglycylated tubulin isoforms, to detect this modification in Giardia extracts and to localize it in the different classes of microtubules within the cell. The alpha- and beta-tubulin subunits were recognized by the two mAbs, indicating that both tubulin subunits are glycylated, in agreement with lately reported mass spectrometry results. Noticeably, Giardia tubulin was much more reactive with AXO 49 than with TAP 952. In situ, AXO 49 intensely labeled the microtubules present in the four pairs of flagella and the median body, and lightly decorated the microtubules from the adhesive disc. In contrast, TAP 952 intensely labeled only the microtubules of the median body. The results indicate a differential expression of glycylated isoforms within various microtubular structures of Giardia lamblia. They also suggest that the complete set of enzymes required for polyglycylation is expressed in very divergent eukaryotes.

Animals↗
PubMed1997

Advances in molecular genetics of alpha-2- and alpha-3/4-fucosyltransferases.

Fucosyltransferases are involved in the last steps of the biosynthesis of ABH and Lewis oligosaccharide antigens. Seven human genes (FUT1 to FUT7) and one pseudogene (Sec 1) have been cloned and localized on different chromosomes (9q34.3; 11q21; 19p13.3 and 19q13.3). Their locations and their high degree of primary sequence identity, suggest that they have appeared by successive duplications followed by translocation and divergent evolution. Their expression is tissue specific and they present a switch during human embryo-foetal development similar to that of hemoglobins. Polymorphic genes FUT1-FUT2 and FUT3-FUT5-FUT6 are organized in two clusters and each gene is partially or totally inactivated by different types of point mutations (nonsense, missense and frame shift), complete gene deletion or a fusion gene. The products of the monomorphic genes FUT4 and FUT7 seem implicated in cell-cell interactions during embryo-foetal development and in the leukocyte adhesion phenomena to endothelial cells in the adult. A phylogenetic tree of the 28 available nucleotide coding sequences of fucosyltransferases has allowed us to situate the duplication events with respect to the separation of species from the main evolutionary path (nematods, birds, mammals, primates and humans). Recently, using a computer approach a general structure of fucosyltransferases has been proposed, inspired from the crystalline structure of the beta-glucosyltransferase of bacteriophage T4. This folding contains two domains with an alternate succession alpha and beta chains. In this model the GDP-fucose binding site would be located between the two domains.

Animals↗
PubMed2003

Ethics of preimplantation diagnosis: recordings from the Fourth International Symposium on Preimplantation Genetics.

New ethical issues emerge from the rapid expansion in knowledge of preimplantation genetics. These were summarized and debated recently during the final session at the Fourth International Symposium on Preimplantation Genetics, held in Cyprus, 10-13 April 2002. Divergent views were expressed on various topics including unique issues in preimplantation genetic diagnosis, the sexing of embryos, cloning and other matters. Differing ethical viewpoints emerged, and alternative ways of coping with certain issues were described. This complex area of ethical and social issues will demand detailed counselling of patients, ongoing debate among professionals, and perhaps legislation or central regulatory authorities to decide on the detailed application of its new technologies.

Animals↗