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Biomedical subjects

G Dreyfuss

Publications and source records attributed to G Dreyfuss.

At least 127 records · Page 7Linked to original sources
PubMed1996

Paramphistomum daubneyi and Fasciola hepatica: the redial burden and cercarial shedding in Lymnaea truncatula subjected to successive unimiracidial cross-exposures.

The development of redial burden and cercarial shedding were studied in two groups of Lymnaea truncatula subjected to successive cross-exposures to one miracidium of Paramphistomum daubneyi and one of Fasciola hepatica per snail, or vice versa. The results were compared with those obtained in controls subjected to two unimiracidial exposures to the same trematode species. The infection rate was 61% in the group cross-exposed to P. daubneyi/F. hepatica and 37% in that cross-exposed to F. hepatica/P. daubneyi; it was 37% in the control group exposed to F. hepatica and 21% in that exposed to P. doubneyi. Snails harboring larval forms of both trematodes were few in number in cross-exposed groups and the redial burden was low, with one trematode dominating over the other. Free cercariae of F. hepatica and those of P. daubneyi were significantly more numerous at day 35 in the group cross-exposed to P. daubneyi/F. hepatica than in the controls or the other cross-exposed group. Mixed cercarial sheddings were obtained from 40% of snails with emission in the group cross-exposed to P. daubneyi/F. hepatica and from 21% of those in the F. hepatica/P. daubneyi group. The numbers of P. daubneyi metacercariae were significantly greater in the group cross-exposed to P. daubneyi/F. hepatica than in the other cross-exposed group, whereas no significant difference in mean numbers was noted for the F. hepatica cysts. Repartition of metacercariae over the patent period was clearly more irregular for P. daubneyi than for the other trematode.

Animals↗
PubMed1996

Signal-mediated nuclear export pathways of proteins and RNAs.

Although it has been known for several years that most nuclear-encoded RNAs and some patients can be exported from the nucleus to the cytoplasm, the molecular mechanisms of these transport processes have been poorly understood. Recently, signals that can induce the rapid and active nuclear export of macromolecules have been identified in the HIV-1 Rev protein, the inhibitor of cAMP-dependent protein kinase (PKI) and the hnRNP A1 protein. Thus, nuclear export appears to be mechanistically similar to nuclear import that it requires specific signal-receptor systems.

Journal Article↗
PubMed1996

The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals.

Nascent pre-mRNAs associate with the abundant heterogeneous nuclear RNP (hnRNP) proteins and remain associated with them throughout the time they are in the nucleus. The hnRNP proteins can be divided into two groups according to their nucleocytoplasmic transport properties. One group is completely restricted to the nucleus in interphase cells, whereas the other group, although primarily nuclear at steady state, shuttles between the nucleus and the cytoplasm. Nuclear export of the shuttling hnRNP proteins is mediated by nuclear export signals (NESs). Mounting evidence indicates that NES-bearing hnRNP proteins are mediators of mRNA export. The hnRNP C proteins are representative of the nonshuttling group of hnRNP proteins. Here we show that hnRNP C proteins are restricted to the nucleus not because they lack an NES, but because they bear a nuclear retention sequence (NRS) that is capable of overriding NESs. The NRS comprises approximately 78 amino acids and is largely within the auxiliary domain of hnRNP C1. We suggest that the removal of NRS-containing hnRNP proteins from pre-mRNA/mRNA is required for mRNA export from the nucleus and is an essential step in the pathway of gene expression.

Amino Acid Sequence↗
PubMed1996

Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them.

Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of mutant FMR1 protein that is impaired in RNA binding. Recently, we described two novel cytoplasmic proteins, FXR1 and FXR2, which are both very similar in amino acid sequence to FMR1 and which also interact strongly with FMR1 and with each other. To understand the function of FMR1 and the FXR proteins, we carried out cell fractionation and sedimentation experiments with monoclonal antibodies to these proteins to characterize the complexes they form. Here, we report that the FMR1 and FXR proteins are associated with ribosomes, predominantly with 60S large ribosomal subunits. The FXR proteins are associated with 60S ribosomal subunits even in cells that lack FMR1 and that are derived from a fragile X syndrome patient, indicating that FMR1 is not required for this association. We delineated the regions of FMR1 that mediate its binding to 60S ribosomal subunits and the interactions among the FMR1-FXR family members. Both regions contain sequences predicted to have a high propensity to form coiled coil interactions, and the sequences are highly evolutionarily conserved in this protein family. The association of the FMR1, FXR1, and FXR2 proteins with ribosomes suggests they have functions in translation or mRNA stability.

Amino Acid Sequence↗
PubMed1996

The development of tissue lesions in the snail Lymnaea glabra exposed to a sublethal dose of molluscicide.

Histological examinations were undertaken in adult Lymnaea glabra to determine whether tissue lesions develop in snails that survived exposure to a molluscicidal agent and thus impair survival or reproduction capacities of remaining snails. The snails were exposed for 4 days to sublethal doses of niclosamide (0.21 mg/L), 3,4-dichloro-2-benzamido-5-nitrothiazole (0.13 mg/L), or 3,5-dichloro-2-benzamido-5-nitrothiazole (0.15 mg/L) at 20 degrees C. After exposure, the surviving snails were maintained under normal conditions (oxygenated water) for a further 21 days. The niclosamide group revealed epithelial necrosis in the digestive glands and the gonads. This was followed by reconstitution from day 12 or 19. The same sequence of tissue lesions also occurred in the kidney, however, a second phase of epithelial necrosis developed in the reconstituted epithelium after day 19. In the two other groups, tissue lesions of the three viscera developed in very similar manner, regardless of the molluscicide chosen for these experiments. Although the molluscicidal doses were sublethal in these snails, 12-19 days at 20 degrees C were required to reconstitute the visceral epithelium. Snails that survived the molluscicidal agent were thus impaired for one week or more in normal conditions.

Animals↗
PubMed1996

The molluscicidal activity of two 2-benzamido-5-nitrothiazole bihalogenated derivatives and niclosamide. Influence of some environmental factors on their toxicity.

Two synthetic molluscicides, 3,4-dichloro-2-benzamido-5-nitrothiazole (3,4-dichloro-BNT) and 3,5-dichloro-BNT, were studied to determine their efficacy against the snail Lymnaea glabra. Results were compared with those of a reference molluscicide, niclosamide. Snail exposure to these chemicals markedly increased overall snail mortality during the experiment (96 h). The LC50 values slightly decreased and, at day 4, were lower for the two BNT derivatives than for niclosamide. The effect of several factors on compound toxicity was also studied using lethal concentrations near LC50. Acclimatization duration under controlled conditions had a variable influence upon overall snail mortality according to the compound. No significant variation in the overall mortality was detected in snail groups exposed to 3,4-dichloro-BNT. On the other hand, snail mortality greatly increased in the 3,5-dichloro-BNT-exposed groups when the duration increased from 24 h to 15 days; the same result was obtained in the niclosamide-exposed snails acclimatized for 8 days. Snail mortality increased in the presence of sand, whatever compound was used, and greatly decreased in the presence of marl; it was also higher with water of low calcium content. When the food supply was low, snail mortality greatly decreased in the niclosamide- and 3,4-dichloro-BNT-exposed groups, whereas it increased in the case of 3,5-dichloro-BNT. In the presence of running water, the number of dead snails with 3,4-dichloro-BNT was identical to that of controls, whereas it was greater with the other molluscicides. These experiments, carried out under controlled conditions, demonstrate that the use of a molluscicide in the field must take into account its chemical properties as well as the characteristics of the snail habitat to optimally eliminate snails.

Adaptation, Physiological↗
PubMed1996

Paramphistomum daubneyi and Fasciola hepatica: the effect of dual infection on prevalence and cercarial shedding in preadult Lymnaea glabra.

Preadult Lymnaea glabra measuring 4-6 mm in height were each exposed to 1 Paramphistomum daubneyi miracidium before being exposed to 1 miracidium of Fasciola hepatica. Total prevalence of infection in the snail groups from 3 different populations ranged from 33% to 39%. In each group, snails harboring larval forms of P. daubneyi, F. hepatica, or both, were noted. If the results from the 3 snail populations are pooled, the total prevalence of snail infection was 13.6% in snails harboring only F. hepatica larvae, 13% in those harboring only P. daubneyi larvae, and 10% in those with both trematodes. Cercarial shedding was obtained from snails harboring F. hepatica larval forms; in the case of snails infected with both trematodes, the mean number of metacercariae ranged from 13 to 21 for F. hepatica, and from 8 to 14 for P. daubneyi. No infected snails were found in snail groups exposed only to 1 trematode miracidia.

Animals↗
PubMed1995

A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway.

Pre-mRNAs are associated with hnRNPs, and these proteins play important roles in the biogenesis of mRNAs. The hnRNP A1 is one of the most abundant hnRNPs, and although localized primarily in the nucleoplasm, shuttles continuously between the nucleus and the cytoplasm. A 38 amino acid domain within A1, termed M9, which bears no resemblance to classical nuclear localization signal (NLS) sequences, localizes A1 to the nucleus. Here we show that M9 is also a nuclear export signal; placing M9 on a protein that is otherwise restricted to the nucleus, the nucleoplasmin core domain (NPc), efficiently exports it to the cytoplasm in a temperature-dependent manner. In contrast, classical NLSs cannot promote the export of NPc. These findings demonstrate that there is a signal-dependent, temperature-sensitive nuclear export pathway and strengthen the suggestion that A1 and other shuttling hnRNPs function as carriers for RNA during export to the cytoplasm.

Amino Acid Sequence↗
PubMed1995

The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo. We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro. This novel protein, FXR2, is very similar to FMR1 (60% identity). FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm. The FXR2 gene is located on human chromosome 17 at 17p13.1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1. Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers. FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome.

Amino Acid Sequence↗
PubMed1995

FXR1, an autosomal homolog of the fragile X mental retardation gene.

Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1.

Amino Acid Sequence↗
PubMed1995

Cell type-specific expression of hnRNP proteins.

HnRNP proteins are abundant nucleoplasmic pre-mRNA-binding proteins which have important roles in the biogenesis of mRNA. Although hnRNP proteins have been extensively characterized in cultured cell lines, little is known about their expression in animal tissues. Here, we have undertaken a systematic survey of the expression of major hnRNP proteins in mouse tissue using specific monoclonal antibodies. Immunohistochemical staining demonstrated that hnRNP proteins C, L, and U were localized to nuclei in all tissues examined. However, cytoplasmic expression of hnRNP A1, D, F/H, and K was also detected in several tissues, suggesting that these proteins have roles in the cytoplasm as well as the nucleus. Importantly, the relative amounts of different hnRNP proteins varied among cell types. This was especially striking in neuronal and reproductive cells. In the brain, certain neuronal cell types contained more hnRNP proteins than glial cells, perhaps reflecting increased levels of neuronal transcription and RNA processing. In the ovary, oocytes contained exceptionally high concentrations of hnRNP proteins as compared to follicular and stromal cells. In the testis, the expression of hnRNP proteins was generally high and was found to be tightly regulated during spermatogenesis. Specifically, hnRNP A1 was highly expressed only in early spermatogonia and absent in later stages. These findings demonstrate that hnRNP proteins do not exist in a fixed stoichiometry across different cell types. Furthermore, as the relative amounts of pre-mRNA-binding proteins (e.g., A1 and ASF/SF2) can affect alternative splicing patterns, the variations that we have observed could profoundly affect cell-specific gene expression.

3T3 Cells↗
PubMed1995

Comparative studies on the productivity of Fasciola gigantica and F. hepatica sporocysts in Lymnaea tomentosa that died after a cercarial shedding or without emission.

A histology study was performed on Fasciola gigantica- or F. hepatica-infected Lymnaea tomentosa that died after a cercarial shedding or without emission to compare the parasite productivity of each trematode. Degenerated rediae increased in number throughout the experiment. Their number rose rapidly after day 79 in snails that died after shedding in the F. gigantica group; they increased more slowly in snails that died without shedding. In the F. hepatica group the number rose after day 63 in the former snails and after day 79 in the latter. The contents of normal rediae evolved inversely. The number of morulae, for example, dropped rapidly after day 79 in the F. gigantica group. In the F. hepatica group it dropped after day 63 in snails that died after shedding and decreased after day 79 in the other dead snails. Free and degenerated cercariae were more numerous in snails that died without emission than in those that died at shedding. They rapidly increased in number after day 77. The numbers of rediae of F. gigantica were substantially greater than those of F. hepatica. In each group considered separately, it was likewise higher in snails that died without shedding than in those that died after the shedding of cercariae.

Animals↗
PubMed1995

A nuclear localization domain in the hnRNP A1 protein.

The heterogeneous nuclear RNP (hnRNP) A1 protein is one of the major pre-mRNA/mRNA binding proteins in eukaryotic cells and one of the most abundant proteins in the nucleus. It is localized to the nucleoplasm and it also shuttles between the nucleus and the cytoplasm. The amino acid sequence of A1 contains two RNP motif RNA-binding domains (RBDs) at the amino terminus and a glycine-rich domain at the carboxyl terminus. This configuration, designated 2x RBD-Gly, is representative of perhaps the largest family of hnRNP proteins. Unlike most nuclear proteins characterized so far, A1 (and most 2x RBD-Gly proteins) does not contain a recognizable nuclear localization signal (NLS). We have found that a segment of ca. 40 amino acids near the carboxyl end of the protein (designated M9) is necessary and sufficient for nuclear localization; attaching this segment to the bacterial protein beta-galactosidase or to pyruvate kinase completely localized these otherwise cytoplasmic proteins to the nucleus. The RBDs and another RNA binding motif found in the glycine-rich domain, the RGG box, are not required for A1 nuclear localization. M9 is a novel type of nuclear localization domain as it does not contain sequences similar to classical basic-type NLS. Interestingly, sequences similar to M9 are found in other nuclear RNA-binding proteins including hnRNP A2.

Amino Acid Sequence↗
PubMed1995

Association of the vav proto-oncogene product with poly(rC)-specific RNA-binding proteins.

We have used the yeast two-hybrid system to isolate proteins that interact with the carboxy-terminal SH3-SH2-SH3 region of Vav. One of the clones encoded heterogeneous nuclear ribonucleoprotein K (hnRNP K), a poly(rC)-specific RNA-binding protein. The interaction between Vav and hnRNP K involves the binding of the most carboxy-terminal SH3 domain of Vav to two proline-rich sequences present in the central region of hnRNP K. Overexpression of Vav in mouse fibroblasts leads to the formation of a stable complex with the endogenous hnRNP K and to the preferential redistribution of this protein to the cytoplasmic fraction. More importantly, Vav and hnRNP K proteins also interact in hematopoietic cells. In addition, Vav associates in vitro with a second 45-kDa poly(rC)-specific RNA-binding protein via its SH3-SH2-SH3 region. These results suggest that Vav plays a role in the regulation of the late steps of RNA biogenesis by modulating the function of poly(rC)-specific ribonucleoproteins.

Amino Acid Sequence↗
PubMed1995

In vivo and in vitro arginine methylation of RNA-binding proteins.

Heterogenous nuclear ribonucleoproteins (hnRNPs) bind pre-mRNAs and facilitate their processing into mRNAs. Many of the hnRNPs undergo extensive posttranslational modifications including methylation on arginine residues. hnRNPs contain about 65% of the total NG,NG-dimethylarginine found in the cell nucleus. The role of this modification is not known. Here we identify the hnRNPs that are methylated in HeLa cells and demonstrate that most of the pre-mRNA-binding proteins receive this modification. Using recombinant human hnRNP A1 as a substrate, we have partially purified and characterized a protein-arginine N-methyltransferase specific for hnRNPs from HeLa cells. This methyltransferase can methylate the same subset of hnRNPs in vitro as are methylated in vivo. Furthermore, it can also methylate other RNA-binding proteins that contain the RGG motif RNA-binding domain. This activity is evolutionarily conserved from lower eukaryotes to mammals, suggesting that methylation has a significant role in the function of RNA-binding proteins.

Amino Acid Sequence↗
PubMed1995

Trypanosoma brucei brucei: antitrypanosomal evaluation of stilbamidinium hexachloroiridiate on the murine CNS model and iridium serum kinetics in infected sheep.

Stilbamidinium hexachloroiridiate was found trypanocidal in vitro against Trypanosoma brucei brucei IPP at 600 microM after a 1 h incubation period and 30 microM after 24 h. This activity was confirmed in mice with a subcutaneous treatment at 20 mg/kg in a single dose. It was then evaluated on T.b. brucei murine CNS model. At the early stage, a subcutaneous treatment at 2 mg/kg/day x 5 cured 50% mice where-as one single dose at 10 mg/kg was completely inactive. Higher doses failed to cure the mice. Nevertheless, hexachloroiridiate salt of stilbamidine was 3.3 fold less toxic than dihydrochloride salt. Although the compound appeared inactive at the late stage of the murine trypanosomiasis, the difference of toxicity justified its evaluation on the early stage of sheep trypanosomiasis. The compound was trypanocidal at 2 mg/kg in a single dose when administered 8 days after infection. The study of iridium serum kinetic showed that stilbamidinium hexachloroiridiate was distributed rapidly according to a monocompartmental model. Moreover, iridium persisted in serum for a long time. The compound in aqueous suspension with 1% carboxymethylcellulose acted therefore as a controlled release system with a bioavailability allowing its trypanocidal action at the early stage.

Animals↗