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S Althoff

Publications and source records attributed to S Althoff.

9 recordsLinked to original sources
PubMed1999

Transport of acetate in mutants of Saccharomyces cerevisiae defective in monocarboxylate permeases.

The strain Saccharomyces cerevisiae W303-1a, able to grow in a medium containing acetic acid as the sole carbon and energy source, was subjected to mutagenesis in order to obtain mutants deficient in monocarboxylate permeases. Two mutant clones exhibiting growth in ethanol, but unable to grow in a medium with acetic acid as the sole carbon and energy source, were isolated (mutants Ace12 and Ace8). In both mutants, the activity for the acetate carrier was strongly affected. The mutant Ace8 revealed not to be affected in the transport of lactate, while the mutant Ace12 did not display activity for that carrier. These results reinforced those previously found in the strain IGC 4072, where two distinct transport systems for monocarboxylates have been described, depending on the growth carbon source. It is tempting to postulate that the Ace8 mutant seems to be affected in the gene coding for an acetate permease. In contrast, the absence of activity for both monocarboxylate permeases in mutant Ace12 could be attributed to a mutation in a gene coding for a regulatory protein not detected before.

Acetates↗
PubMed1998

Isolation and characterization of Kluyveromyces marxianus mutants deficient in malate transport.

In malic acid-grown cells of the strains ATCC 10022 and KMS3 of Kluyveromyces marxianus the transport of malic acid occurred by a malate-proton symport, which accepted L-malic, D-malic, succinic and fumaric acids, but not tartaric, malonic or maleic acids. The system was inducible and subjected to glucose repression. Mutants of the strain KMS3, unable to grow in a medium with malic acid, were isolated and checked for their capacity to utilize several carbon sources and to transport dicarboxylic acids by the malate-proton symport. Two distinct clones affected on malate transport were obtained. Both were able to grow on a medium with glycerol or ethanol but not with DL-malic, succinic, oxoglutaric and oxaloacetic acids as the sole carbon and energy sources. However, while one of the mutants (Mal7) displayed activity levels for the enzymes malate dehydrogenase, isocitrate lyase, and phosphoenolpyruvate carboxykinase similar to those of the wild strain, in the other mutant type (Mal6) the activities for the same enzymes were significantly reduced. Plasma membranes from derepressed cells of the wild strain and of the mutants Mal6 and Mal7 were isolated and the protein analysed by SDS-PAGE. The electrophoretic patterns of these preparations differed in a polypeptide with an apparent molecular mass of about 28 kDa, which was absent only in the mutant Mal7. The results indicated that Mal7 can be affected in a gene that encodes a malate carrier in K. marxianus.

Biological Transport↗
PubMed1998

Postexcitatory inhibition after transcranial magnetic stimulation of the motor cortex in patients with drug-induced parkinsonism and in healthy individuals.

The duration of the postexcitatory inhibition after transcranial magnetic stimulation was investigated in 16 patients with drug-induced parkinsonism and in 20 healthy control individuals. In the patients, the chlorpromazine-equivalent of the neuroleptic medication was determined, and the severity of the drug-induced parkinsonism was measured using the Simpson-Angus Scale score. Group comparison (U-test) revealed a significant shorter postexcitatory inhibition in patients than in control individuals. Regression analyses showed a negative correlation between the Simpson-Angus scale score and the duration of the postexcitatory inhibition. The correlation only reached significance for a group of patients who received at least one butyrophenone derivate. No clear-cut relation was found between the chlorpromazine equivalent and the postexcitatory inhibition. These results indicate that drug-induced parkinsonism shares features of genuine Parkinson's disease. Furthermore, it seems possible to assess the extrapyramidal side effect of butyrophenone derivates, but not for other neuroleptic drugs, by means of the method described.

Adult↗
PubMed1994

Genetic and biochemical analysis of the fission yeast ribonucleoprotein particle containing a homolog of Srp54p.

Mammalian signal recognition particle (SRP), a complex of six polypeptides and one 7SL RNA molecule, is required for targeting nascent presecretory proteins to the endoplasmic reticulum (ER). Earlier work identified a Schizosaccharomyces pombe homolog of human SRP RNA and showed that it is a component of a particle similar in size and biochemical properties to mammalian SRP. The recent cloning of the gene encoding a fission yeast protein homologous to Srp54p has made possible further characterization of the subunit structure, subcellular distribution, and assembly of fission yeast SRP. S. pombe SRP RNA and Srp54p co-sediment on a sucrose velocity gradient and coimmunoprecipitate, indicating that they reside in the same complex. In vitro assays demonstrate that fission yeast Srp54p binds under stringent conditions to E. coli SRP RNA, which consists essentially of domain IV, but not to the full-length cognate RNA nor to an RNA in which domain III has been deleted in an effort to mirror the structure of bacterial homologs. Moreover, the association of S. pombe Srp54p with SRP RNA in vivo is disrupted by conditional mutations not only in domain IV, which contains its binding site, but in domains I and III, suggesting that the particle may assemble cooperatively. The growth defects conferred by mutations throughout SRP RNA can be suppressed by overexpression of Srp54p, and the degree to which growth is restored correlates inversely with the severity of the reduction in protein binding. Conditional mutations in SRP RNA also reduce its sedimentation with the ribosome/membrane pellet during cell fractionation. Finally, immunoprecipitation under native conditions of an SRP-enriched fraction from [35S]-labeled fission yeast cells suggests that five additional polypeptides are complexed with Srp54p; each of these proteins is similar in size to a constituent of mammalian SRP, implying that the subunit structure of this ribonucleoprotein is conserved over vast evolutionary distances.

Base Sequence↗
PubMed1994

Molecular evolution of SRP cycle components: functional implications.

Signal recognition particle (SRP) is a cytoplasmic ribonucleoprotein that targets a subset of nascent presecretory proteins to the endoplasmic reticulum membrane. We have considered the SRP cycle from the perspective of molecular evolution, using recently determined sequences of genes or cDNAs encoding homologs of SRP (7SL) RNA, the Srp54 protein (Srp54p), and the alpha subunit of the SRP receptor (SR alpha) from a broad spectrum of organisms, together with the remaining five polypeptides of mammalian SRP. Our analysis provides insight into the significance of structural variation in SRP RNA and identifies novel conserved motifs in protein components of this pathway. The lack of congruence between an established phylogenetic tree and size variation in 7SL homologs implies the occurrence of several independent events that eliminated more than half the sequence content of this RNA during bacterial evolution. The apparently non-essential structures are domain I, a tRNA-like element that is constant in archaea, varies in size among eucaryotes, and is generally missing in bacteria, and domain III, a tightly base-paired hairpin that is present in all eucaryotic and archeal SRP RNAs but is invariably absent in bacteria. Based on both structural and functional considerations, we propose that the conserved core of SRP consists minimally of the 54 kDa signal sequence-binding protein complexed with the loosely base-paired domain IV helix of SRP RNA, and is also likely to contain a homolog of the Srp68 protein. Comparative sequence analysis of the methionine-rich M domains from a diverse array of Srp54p homologs reveals an extended region of amino acid identity that resembles a recently identified RNA recognition motif. Multiple sequence alignment of the G domains of Srp54p and SR alpha homologs indicates that these two polypeptides exhibit significant similarity even outside the four GTPase consensus motifs, including a block of nine contiguous amino acids in a location analogous to the binding site of the guanine nucleotide dissociation stimulator (GDS) for E. coli EF-Tu. The conservation of this sequence, in combination with the results of earlier genetic and biochemical studies of the SRP cycle, leads us to hypothesize that a component of the Srp68/72p heterodimer serves as the GDS for both Srp54p and SR alpha. Using an iterative alignment procedure, we demonstrate similarity between Srp68p and sequence motifs conserved among GDS proteins for small Ras-related GTPases. The conservation of SRP cycle components in organisms from all three major branches of the phylogenetic tree suggests that this pathway for protein export is of ancient evolutionary origin.

Amino Acid Sequence↗
PubMed1992

Random mutagenesis of Schizosaccharomyces pombe SRP RNA: lethal and conditional lesions cluster in presumptive protein binding sites.

Signal recognition particle (SRP), a ribonucleoprotein composed of six polypeptides and one RNA subunit, serves as an adaptor between the cytoplasmic protein synthetic machinery and the translocation apparatus of the endoplasmic reticulum. To begin constructing a functional map of the 7SL RNA component of SRP, we extensively mutagenized the Schizosaccharomyces pombe SRP7 gene. Phenotypes are reported for fifty-two mutant alleles derived from random point mutagenesis, seven alleles created by site-directed mutagenesis to introduce restriction sites into the SRP7 gene, nine alleles designed to pinpoint conditional lesions, and three alleles with extra nucleotides inserted at position 84. Our data indicate that virtually all single nucleotide changes as well as many multiple substitutions in this highly structured RNA are phenotypically silent. Six lethal alleles and eleven which result in sensitivity to the combination of high temperature and elevated osmotic strength were identified. These mutations cluster in conserved regions which, in the mammalian RNA, are protected from nucleolytic agents by SRP proteins. The effects of mutations in the presumptive binding site for a fission yeast SRP 9/14 homolog indicate that both the identity of a conserved residue and the secondary structure within which it is embedded are functionally important. The phenotypes of mutations in Domain IV suggest particular residues as base-specific contacts for the fission yeast SRP54 protein. A single allele which confers temperature-sensitivity in the absence of osmotic perturbants was identified in this study; the growth properties of the mutant strain suggest that the encoded RNA is somewhat defective even at the permissive temperature, and is most likely unable to correctly assemble with SRP proteins at the nonpermissive temperature.

Alleles↗
PubMedDate not supplied

Inhibitory period and late muscular responses after transcranial magnetic stimulation in healthy children.

Transcranial magnetic stimulation (TMS) was investigated in 24 healthy children between the ages of 3 and 14 years in order to study late muscular responses (as they are observed in adults) as a function of age and maturation. Muscular responses were recorded bilaterally from the biceps muscle. An early muscular response and several late phenomena can be elicited in children. (i) An inhibitory period following the primary response could preferentially be recorded contralaterally. (ii) During facilitation, a late response was recorded bilaterally. (iii) Without facilitation (during 'relaxation'), late responses were recorded bilaterally with a latency of between 50-400 ms. The latency of the latter responses depended on the age of the children, and may therefore be useful in monitoring the maturation of the central motor system in infants. Due to small side-to-side differences, the inhibitory period may be of diagnostic value in children for detection of unilateral dysfunction of the central nervous system.

Adolescent↗
PubMedDate not supplied

[Griscelli syndrome: a case report].

BACKGROUND: Griscelli syndrome is a rare disorder with poor prognosis. It is characterized by silver-grey hair or strands of silver-grey hair in childhood, and variable cellular immunodeficiency. The course of the untreated disease is fatal. Recurrent episodes of fever and lymphohistocytic infiltration of organs lead to hepatosplenomegaly, lymphadenopathy, pancytopenia, and progressive neurological impairment. Prognosis on morbidity and lethality depends on an early diagnosis. PATIENT: The girl we report on suffers from Griscelli syndrome. She developed normally and only her grey strands of hair, grey eyebrows, and eyelids were conspicuous. With the age of 4 years, she presented with a first episode of illness. RESULTS: Cytostatic treatment seemed to ameliorate the course of the disease although further accelerated phases could not be prevented. The only therapeutic option is a bone marrow transplantation, which we conferred upon our patient. CONCLUSION: The finding of grey hairs in childhood should alert clinicians to consider Griscelli syndrome since an early diagnosis is life and health saving.

Administration, Oral↗