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Biomedical subjects

G Dreyfuss

Publications and source records attributed to G Dreyfuss.

At least 109 records · Page 6Linked to original sources
PubMed1997

Paramphistomum daubneyi: the development of redial generations in the snail Lymnaea truncatula.

Rediae of Paramphistomum daubneyi were counted and measured in Lymnaea truncatula to elucidate the variability in the numbers of free rediae and cercariae occurring between naturally infected snails and experimental single-miracidium infections. Experiments were performed using one miracidium per snail and snail raising was carried out at 20 degrees C. Two redial generations succeeded each other in the snail until day 49. A mean of 8-10 rediae differentiated in the sporocyst at days 7 and 14; the remaining germ balls and redial embryos decreased in number after day 21. First-generation rediae became free in the snail's body starting at day 14 and their number increased to a mean of 7.5 at day 49, with a maximum of 10 rediae being detected in 1 snail. They produced second-generation rediae, which exited from the body starting at day 28, and then cercariae, which exited from day 42 onward. The count of second-generation rediae was 6-6.2/snail at day 49, with a maximum of 12 being detected in 1 snail; they produced only cercariae.

Animals↗
PubMed1997

Fasciola hepatica: in vitro production of daughter rediae and cercariae from first- and second-generation rediae.

Fasciola hepatica mother rediae belonging to the first generation and the first cohort of the second generation were extracted from their snail intermediate host (Lymnaea truncatula) and maintained in vitro for 16 days to determine the quantity of daughter rediae and cercariae produced by each generation. L-15 Leibovitz medium with a saline fraction adjusted to that of the L. truncatula hemolymph was used for experiments. A total of 35 daughter rediae exited from the 21 mother rediae of the first and second generations, which were 14-32 days old at the onset of culture. Microscope examination of the mother rediae demonstrated the presence of numerous redial embryos and differentiating daughter rediae, whereas no cercaria was seen within their body. A total of 49 cercariae exited from the 17 mother rediae of the first and second generations, which were 29-50 days old at the onset of culture. No differentiating daughter redia was seen in these last mother rediae. The productivity of the first or second generation (first cohort) was nearly identical in terms of cercariae.

Animals↗
PubMed1997

Nuclear export of proteins and RNAs.

Our understanding of protein export from the nucleus to the cytoplasm has been advanced recently by the discovery of active, signal-mediated export pathways. Nuclear export signals have been identified in several proteins, the majority of which are RNA-binding proteins. Nuclear export of RNA molecules is likely to be driven by protein-based nuclear export signals.

Amino Acid Sequence↗
PubMed1997

RNA-binding proteins as regulators of gene expression.

A plethora of post-transcriptional mechanisms are involved in essential steps in the pathway of genetic information expression in eukaryotes. These processes are specified by cis-acting signals on RNAs and are mediated by specific trans-acting factors, including RNA-binding proteins and small complementary RNAs. Recent information has begun to define the molecular mechanisms by which RNA-binding proteins recognize specific RNA sequences and influence the processing and function of RNA molecules.

Amino Acid Sequence↗
PubMed1997

Correlation between severity and SMN protein level in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord. Three different forms of childhood SMA have been recognized on the basis of age at onset and clinical course: Werdnig-Hoffmann disease (type-1), the intermediate form (type-II) and Kugelberg-Welander disease (type-III). A gene termed 'survival of motor neuron' (SMN) has been recognized as the disease-causing gene in SMA. SMN encodes a protein located within a novel nuclear structure and interacts with RNA-binding proteins. To elucidate the molecular mechanism underlying the pathogenesis of the disease, we examined the expression of the SMN gene in both controls and SMA patients by western blot and immunohistochemical analyses using antibodies raised against the SMN protein. The present study shows a marked deficiency of the SMN protein in SMA.

Blotting, Western↗
PubMed1997

Trypanocidal effect of Ir-(COD)-pentamidine tetraphenylborate on Trypanosoma brucei and T. b. gambiense rodent models and serum kinetics in sheep.

Pentamidine di-(iridium cyclo-octadiene)tetraphenylborate, called Ir-(COD)-pentamidine tetraphenylborate, was selected from a primary screening as a promising trypanocidal compound. The compound was evaluated against three isolates: Trypanosoma brucei brucei CMP, T.b. brucei GVR 35 and T.b. gambiense Feo. On the T.b. brucei GVR 35 murine CNS model, no mouse was cured when the treatment was commenced 21 days post-infection whatever the treatment regimen. Nevertheless, in vitro the compound killed the trypomastigote forms of T. b. gambiense Feo at 0.6 microM. In vivo, the compound cured all mice infected 1 hour previously with T. b. gambiense Feo after a 10 mg/kg (6.3 mumol/kg) treatment subcutaneously administered in a single dose. Moreover, the compound was active at 1 mg/kg (0.6 mumol/kg) in a single dose against the early stage of the T. b. brucei Antat 1-9 sheep model. Serum kinetics data showed that pentamidine di-(iridium cyclo-octadiene) tetraphenylborate was distributed within deep compartment according to a monocompartmental model. The maximum iridium serum concentration was 198 micrograms/l corresponding to 1 mumol/kg of iridium derivative and this value remained stable for 30-50 hours post-treatment. Iridium was completely eliminated from the serum 700 hours post-treatment. all data obtained from these models are in favour of an activity in the early stage of the disease but indicate that the compound could not cross the blood-brain barrier despite its lipophilicity. Although iterative treatments with the compound rapidly induced the selection of iridium derivative refractory populations, the compound could be studied on pentamidine refractory strains.

Animals↗
PubMed1997

RNA transport.

RNA molecules synthesized in the nucleus are transported to their sites of function throughout the eukaryotic cell by specific transport pathways. This review focuses on transport of messenger RNA, small nuclear RNA, ribosomal RNA, and transfer RNA between the nucleus and the cytoplasm. The general molecular mechanisms involved in nucleocytoplasmic transport of RNA are only beginning to be understood. However, during the past few years, substantial progress has been made. A major theme that emerges from recent studies of RNA transport is that specific signals mediate the transport of each class of RNA, and these signals are provided largely by the specific proteins with which each RNA is associated.

Animals↗
PubMed1997

Fasciola gigantica and F hepatica: a comparative study of some characteristics of Fasciola infection in Lymnaea truncatula infected by either of the two trematodes.

Experimental infections were carried out using three Lymnaea truncatula populations and two Fasciola species in order to determine the trematode influence on six parameters of snail infection by either of the two trematodes. All experiments were performed using snails 4 mm long, two miracidia for each L truncatula, and a constant temperature of 20 degrees C. No significant influence of trematode species was detected in the following parameters: snail survival at day 30, the life span of infected snails (from miracidial exposure to snail death), the increase in shell length throughout the experiment, the duration of the patent period and the number of cercariae shed by infected snails. The frequency of cercaria-shedding snails was closely correlated with the particular L truncatula population and trematode species. A similar finding in two populations was also noted for the frequencies found in the infected snails who died without emission. The prepatent period had a longer duration in the Fasciola gigantica-infected groups. The percentages of floating cysts were greater in the Fasciola gigantica groups than in the Fasciola hepatica groups.

Animals↗
PubMed1997

YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity.

The complexity of eukaryotic mRNA processing suggests a need for certain factors, called RNA chaperones, that can modulate RNA secondary structure as well as the interactions between pre-mRNA and trans-acting components. To identify factors that may fulfill this role in the yeast Saccharomyces cerevisiae, we fractionated whole-cell extracts and assayed for activity that could facilitate a specific RNA-RNA annealing reaction. We detected one strong RNA annealing activity and purified it to homogeneity. This previously undescribed factor, Yra1p, is localized to the nucleus; its sequence contains one RNP-motif RNA-binding domain. The YRA1 gene contains a 766-nt intron, the second-largest identified in this organism, and Yra1p serves an essential, nonredundant function. Taken together, our findings indicate that Yra1p is likely to have an important role in S. cerevisiae nuclear pre-mRNA metabolism.

Amino Acid Sequence↗
PubMed1996

General RNA binding proteins render translation cap dependent.

Translation in rabbit reticulocyte lysate is relatively independent of the presence of the mRNA m7G cap structure and the cap binding protein, eIF-4E. In addition, initiation occurs frequently at spurious internal sites. Here we show that a critical parameter which contributes to cap-dependent translation is the amount of general RNA binding proteins in the extract. Addition of several general RNA binding proteins, such as hnRNP A1, La autoantigen, pyrimidine tract binding protein (hnRNP I/PTB) and the major core protein of cytoplasmic mRNP (p50), rendered translation in a rabbit reticulocyte lysate cap dependent. These proteins drastically inhibited the translation of an uncapped mRNA, but had no effect on translation of a capped mRNA. Based on these and other results, we suggest that one function of general mRNA binding proteins in the cytoplasm is to promote ribosome binding by a 5' end, cap-mediated mechanism, and prevent spurious initiations at aberrant translation start sites.

Animals↗
PubMed1996

Transportin: nuclear transport receptor of a novel nuclear protein import pathway.

Many nuclear proteins are imported into the cell nucleus by the "classical" nuclear localization signal (NLS)-mediated import pathway. In this pathway, a sequence rich in basic residues in the protein interacts with a heterodimeric complex termed importin and this, along with the GTPase Ran, mediates nuclear import of the NLS-bearing protein. The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein contains a novel nuclear localization sequence, termed M9, that does not contain any clusters of basic residues. Very recently, we showed that M9 directs import into the nucleus by a novel protein import pathway distinct from the classical NLS pathway. A 90-kilodalton protein termed transportin was identified as a protein that specifically interacts with wild-type M9 but not transport-defective M9 mutants. Transportin and an ATP-regenerating system were found to be necessary and sufficient for import of M9-containing proteins in an in vitro import assay. In this report, we provide additional evidence that transportin can interact directly with M9-containing proteins and also show that it can mediate import of full-length hnRNP A1. In addition, Ran, or a Ran-binding protein, is identified as a second protein component of this novel nuclear import pathway. Transportin relatives from Saccharomyces cerevisiae which likely serve as additional nuclear transport receptors are described.

Amino Acid Sequence↗
PubMed1996

Heteronuclear ribonucleoproteins C1 and C2, components of the spliceosome, are specific targets of interleukin 1beta-converting enzyme-like proteases in apoptosis.

Apoptosis induced by a variety of agents results in the proteolytic cleavage of a number of cellular substrates by enzymes related to interleukin 1beta-converting enzyme (ICE). A small number of substrates for these enzymes have been identified to date, including enzymes involved in DNA repair processes: poly(ADP-ribose) polymerase and DNA-dependent protein kinase. We describe here for the first time the specific cleavage of the heteronuclear ribonucleoproteins (hnRNPs) C1 and C2 in apoptotic cells induced to undergo apoptosis by a variety of stimuli, including ionizing radiation, etoposide, and ceramide. No cleavage was observed in cells that are resistant to apoptosis induced by ionizing radiation. Protease inhibitor data implicate the involvement of an ICE-like protease in the cleavage of hnRNP C. Using recombinant ICE-like proteases and purified hnRNP C proteins in vitro, we show that the C proteins are cleaved by Mch3alpha and CPP32 and, to a lesser extent, by Mch2alpha, but not by ICE, Nedd2, Tx, or the cytotoxic T-cell protease granzyme B. The results described here demonstrate that the hnRNP C proteins, abundant nuclear proteins thought to be involved in RNA splicing, belong to a critical set of protein substrates that are cleaved by ICE-like proteases during apoptosis.

Apoptosis↗
PubMed1996

A novel receptor-mediated nuclear protein import pathway.

Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRNP A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-mediated nuclear import occurs by a novel pathway that is independent of the well-characterized, importin-mediated classical NLS pathway. Additionally, we have identified a specific M9-interacting protein, termed transportin, which binds to wild-type M9 but not to transport-defective M9 mutants. Transportin is a 90 kDa protein, distantly related to importin beta, and we show that it mediates the nuclear import of M9-containing proteins. These findings demonstrate that there are at least two receptor-mediated nuclear protein import pathways. Furthermore, as hnRNP A1 likely participates in mRNA export, it raises the possibility that transportin is a mediator of this process as well.

Amino Acid Sequence↗
PubMed1996

A novel nuclear structure containing the survival of motor neurons protein.

Spinal muscular atrophy (SMA) is a common, often fatal, autosomal recessive disease leading to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. A gene termed survival of motor neurons (SMN), at 5q13, has been identified as the determining gene of SMA (Lefebvre et al., 1995). The SMN gene is deleted in > 98% of SMA patients, but the function of the SMN protein is unknown. In searching for hnRNP-interacting proteins we found that SMN interacts with the RGG box region of hnRNP U, with itself, with fibrillarin and with several novel proteins. We have produced monoclonal antibodies to the SMN protein, and we report here on its striking cellular localization pattern. Immunolocalization studies using SMN monoclonal antibodies show several intense dots in HeLa cell nuclei. These structures are similar in number (2-6) and size (0.1-1.0 micron) to coiled bodies, and frequently are found near or associated with coiled bodies. We term these prominent nuclear structures gems, for Gemini of coiled bodies.

3T3 Cells↗
PubMed1996

Distinct domains in ribosomal protein L5 mediate 5 S rRNA binding and nucleolar localization.

Ribosomal protein L5, a 34-kDa large ribosomal subunit protein, binds to 5 S rRNA and has been implicated in the intracellular transport of 5 S rRNA. By immunofluorescence microscopy, L5 is detected mostly in the nucleolus with a fainter signal in the nucleoplasm, and it is known to also be a component of large ribosomal subunits in the cytoplasm. 5 S rRNA is transcribed in the nucleoplasm, and L5 is thought to play an important role in delivering 5 S rRNA to the nucleolus. Using RNA-binding assays and transfection experiments, we have delineated the domains within L5 that confer its 5 S rRNA binding activity and that localize it to the nucleolus. We found that the amino-terminal 93 amino acids are necessary and sufficient to bind 5 S rRNA in vitro, while the carboxyl-terminal half of the protein, comprising amino acids 151-296, serves to localize the protein to the nucleolus. L5, therefore, has a modular domain structure reminiscent of other RNA transport proteins where one region of the molecule serves to bind RNA while another determines subcellular localization.

Amino Acid Sequence↗
PubMed1996

Growth modification of Euglena gracilis Klebs after 2-benzamido-5-nitrothiazole derivatives application.

The toxic effect of 2-benzamido-5-nitrothiazole (BNT) and 11 of its derivatives on the growth of Euglena gracilis was studied in vitro and compared with that of niclosamide. These compounds inhibit proliferation of algae or, at low concentrations, stimulate proliferation. BNT and all its derivatives had an inhibiting effect that was less pronounced, however, than with niclosamide in most instances. The most active compounds were 3,5-dichloro-BNT at pH 3.5 and 7.2. Growth activation was studied by determining the maximal activation concentration. BNT and its derivatives stimulated E. gracilis growth at low concentrations in an acidic environment. This effect was more variable in an environment at neutral pH.

Animals↗
PubMed1996

The Effect of Parasitism by Fasciola hepatica and Muellerius capillaris on the Nerve Ganglia of Lymnaea truncatula

Morphometric and histopathological studies were performed in Lymnaea truncatula experimentally infected by Fasciola hepatica or Muellerius capillaris between Days 30 and 60 postinfection. In the pedal ganglia, snail parasitism had a significant influence on the decrease in length and the increase in width in the M. capillaris group. In the dorsal lobes of cerebral ganglia, snail parasitism had a significant influence on the decrease in lobe width in the F. hepatica group and the increase in width in the M. capillaris group. In the two groups of infected snails, snail parasitism had a significant influence on the decrease in the number of neurons in the pedal ganglia and the dorsal lobes of the cerebral ganglia. The other ganglia and lobes did not demonstrate any significant differences in the size or number of neurons. Infected snails of both groups had multifocal nerve lesions, i.e. (a) dyskariosis with occasionally eccentric nuclei and (b) cell lysis with only cell remnants present.

Journal Article↗