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S Guth

Publications and source records attributed to S Guth.

At least 19 recordsLinked to original sources
PubMed2004

[Tasks and functions of the "Senate Commission for the Evaluation of Healthy Harmless aspects of Food" of the German Research Foundation].

The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) advises authorities and the government on food safety. The risk assessment of foodstuffs, including novel and functional foods, covers the evaluation of food ingredients and additives as well as the evaluation of novel processing methods. In carrying out this task the Commission expresses its opinion primarily on those aspects which are concerned with the safety assessment. In addition, questions relating to the technological need and to nutritional or physiological benefits are also considered. The topics considered may originate from enquiries of the Ministry for Consumer Protection, Nutrition and Agriculture (BMVEL). Other topics may be selected by the Commission on its own initiative, if they are considered to be of particular importance for consumer protection. Within the context of this activity the SKLM also organises symposia and expert discussions, their outcome subsequently being published as resolutions, conclusions or opinions.

Advisory Committees↗
PubMed2001

The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element.

The generation of >30 different HIV-1 mRNAs is achieved by alternative splicing of one primary transcript. The removal of the second tat intron is regulated by a combination of a suboptimal 3' splice site and cis-acting splicing enhancers and silencers. Here we show that hnRNP A1 inhibits splicing of this intron via a novel heterogeneous nuclear ribonucleoprotein (hnRNP) A1-responsive intron splicing silencer (ISS) that can function independently of the previously characterized exon splicing silencer (ESS3). Surprisingly, depletion of hnRNP A1 from the nuclear extract (NE) enables splicing to proceed in NE that contains 100-fold reduced concentrations of U2AF and normal levels of SR proteins, conditions that do not support processing of other efficiently spliced pre-mRNAs. Reconstituting the extract with recombinant hnRNP A1 protein restores splicing inhibition at a step subsequent to U2AF binding, mainly at the time of U2 snRNP association. hnRNP A1 interacts specifically with the ISS sequence, which overlaps with one of three alternative branch point sequences, pointing to a model where the entry of U2 snRNP is physically blocked by hnRNP A1 binding.

Alternative Splicing↗
PubMed2001

Dual function for U2AF(35) in AG-dependent pre-mRNA splicing.

The splicing factor U2AF is required for the recruitment of U2 small nuclear RNP to pre-mRNAs in higher eukaryotes. The 65-kDa subunit of U2AF (U2AF(65)) binds to the polypyrimidine (Py) tract preceding the 3' splice site, while the 35-kDa subunit (U2AF(35)) contacts the conserved AG dinucleotide at the 3' end of the intron. It has been shown that the interaction between U2AF(35) and the 3' splice site AG can stabilize U2AF(65) binding to weak Py tracts characteristic of so-called AG-dependent pre-mRNAs. U2AF(35) has also been implicated in arginine-serine (RS) domain-mediated bridging interactions with splicing factors of the SR protein family bound to exonic splicing enhancers (ESE), and these interactions can also stabilize U2AF(65) binding. Complementation of the splicing activity of nuclear extracts depleted of U2AF by chromatography in oligo(dT)-cellulose requires, for some pre-mRNAs, only the presence of U2AF(65). In contrast, splicing of a mouse immunoglobulin M (IgM) M1-M2 pre-mRNA requires both U2AF subunits. In this report we have investigated the sequence elements (e.g., Py tract strength, 3' splice site AG, ESE) responsible for the U2AF(35) dependence of IgM. The results indicate that (i) the IgM substrate is an AG-dependent pre-mRNA, (ii) U2AF(35) dependence correlates with AG dependence, and (iii) the identity of the first nucleotide of exon 2 is important for U2AF(35) function. In contrast, RS domain-mediated interactions with SR proteins bound to the ESE appear to be dispensable, because the purine-rich ESE present in exon M2 is not essential for U2AF(35) activity and because a truncation mutant of U2AF(35) consisting only of the pseudo-RNA recognition motif domain and lacking the RS domain is active in our complementation assays. While some of the effects of U2AF(35) can be explained in terms of enhanced U2AF(65) binding, other activities of U2AF(35) do not correlate with increased cross-linking of U2AF(65) to the Py tract. Collectively, the results argue that interaction of U2AF(35) with a consensus 3' splice site triggers events in spliceosome assembly in addition to stabilizing U2AF(65) binding, thus revealing a dual function for U2AF(35) in pre-mRNA splicing.

Binding Sites↗
PubMed2000

Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after polypyrimidine tract recognition by U2AF.

Two sequences important for pre-mRNA splicing precede the 3' end of introns in higher eukaryotes, the branch point (BP) and the polypyrimidine (Py) tract. Initial recognition of these signals involves cooperative binding of the splicing factor SF1/mammalian branch point binding protein (mBBP) to the BP and of U2AF(65) to the Py tract. Both factors are required for recruitment of the U2 small nuclear ribonucleoprotein particle (U2 snRNP) to the BP in reactions reconstituted from purified components. In contrast, extensive depletion of ST1/BBP in Saccharomyces cerevisiae does not compromise spliceosome assembly or splicing significantly. As BP sequences are less conserved in mammals, these discrepancies could reflect more stringent requirements for SF1/BBP in this system. We report here that extensive depletion of SF1/mBBP from nuclear extracts of HeLa cells results in only modest reduction of their activity in spliceosome assembly and splicing. Some of these effects reflect differences in the kinetics of U2 snRNP binding. Although U2AF(65) binding was reduced in the depleted extracts, the defects caused by SF1/mBBP depletion could not be fully restored by an increase in occupancy of the Py tract by exogenously added U2AF(65), arguing for a role of SF1/mBBP in U2 snRNP recruitment distinct from promoting U2AF(65) binding.

Amino Acid Sequence↗
PubMed2000

The structure of ribonuclease P protein from Staphylococcus aureus reveals a unique binding site for single-stranded RNA.

Ribonuclease P (RNaseP) catalyses the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5' terminus. The prokaryotic RNaseP holoenzyme consists of a catalytic RNA component and a protein subunit (RNaseP protein), which plays an auxiliary but essential role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme. We determined the three-dimensional high-resolution structure of the RNaseP protein from Staphylococcus aureus (117 amino acid residues) by nuclear magnetic resonance (NMR) spectroscopy in solution. The protein has an alphabeta-fold, similar to the ribonucleoprotein domain. We used small nucleic acid molecules as a model for the 5'-leader sequence to probe the propensity for generic single-stranded RNA binding on the protein surface. The NMR results reveal a contiguous interaction site, which is identical with the previously identified leader sequence binding site in RNaseP holoenzyme. The conserved arginine-rich motif does not bind single-stranded RNA. It is likely that this peptide segment binds selectively to double-stranded sections of P RNA, which are conformationally more rigid. Given the essentiality of RNaseP for the viability of the organism, knowledge of the S. aureus protein structure and insight into its interaction with RNA will help us to develop RNaseP and RNaseP protein as targets for novel antibiotics against this pathogen.

Amino Acid Sequence↗
PubMed2000

A model of stepwise isovolaemic blood exchange in anaesthetised, spontaneously breathing rats to evaluate the oxygen transport efficiency of artificial oxygen carriers.

Our research pursues the production of hypo-oncotic artificial oxygen carriers, based on artificial covalently cross-linked hyperpolymeric mammalian haemoglobins. To evaluate their in vivo efficiency in oxygen delivery to the tissue we developed a small animal model of stepwise isovolaemic blood exchange in anaesthetised, spontaneously breathing rats. With the aid of a two-way respiratory micro valve for small animals the overall oxygen uptake by the tissue of the animal can be determined. Measurements of oxygen contents in arterial and mixed venous blood and of some further blood parameters together with known oxygen-binding characteristics of artificial and native oxygen carriers, permits the determination of the way the two oxygen carriers contribute to the overall oxygen uptake. These so-called partial oxygen net to transport rates (i.e. partial oxygen uptakes), related to the corresponding intravascular mass flow of the transporters, are characteristic measures of the efficiency of the oxygen transporter, the so-called oxygen transport quality. Other biological indicators for an adequate oxygen supply are oxygen-dependent changes of ventilation, cardiac output, heart rate, and systemic vascular resistance. The performance of artificial oxygen carriers is elucidated by a comparison with experimental results from the analogous treatment of rats with non oxygen-transporting plasma expanders.

Anesthesia↗
PubMed2000

[Helical CT of urinary tract: clinical applications].

Helical CT is the most useful imaging modality to evaluate kidney diseases. Different imaging protocols are used to assess the correct diagnosis in each clinical situation. The nephrographic phase (between 90 and 100 s of delay after injection) is more accurate than the cortical phase (between 30 and 40 s of delay) to depict and characterise small renal masses. Multiplanar and 3D reconstruction are useful to plan partial kidney surgery or percutaneous surgery of lithiasis. In emergency, spiral CT, if available, is suitable to assess renal colic. Spiral CT is the best modality to evaluate traumatic kidney.

Colic↗
PubMed2000

[Vesical diseases: accuracy of imaging modalities].

Vesical disorders are numerous. For tumoral processes, the role of imaging modalities is limited to the loco-regional extension. In certain rare cases of benign tumors, precise diagnosis can be evocated. Nowadays, urinary insufficiency is explored by dynamic MRI. It provides a complete assessment of the whole muscular and visceral compartments of the pelvic cavity.

Cystitis↗
PubMed1999

Inhibition of msl-2 splicing by Sex-lethal reveals interaction between U2AF35 and the 3' splice site AG.

The protein Sex-lethal (SXL) controls dosage compensation in Drosophila by inhibiting the splicing and translation of male-specific-lethal-2 (msl-2) transcripts. Here we report that splicing inhibition of msl-2 requires a binding site for SXL at the polypyrimidine (poly(Y)) tract associated with the 3' splice site, and an unusually long distance between the poly(Y) tract and the conserved AG dinucleotide at the 3' end of the intron. Only this combination allows efficient blockage of U2 small nuclear ribonucleoprotein particle binding and displacement of the large subunit of the U2 auxiliary factor (U2AF65) from the poly(Y) tract by SXL. Crosslinking experiments with ultraviolet light indicate that the small subunit of U2AF (U2AF35) contacts the AG dinucleotide only when located in proximity to the poly(Y) tract. This interaction stabilizes U2AF65 binding such that SXL can no longer displace it from the poly(Y) tract. Our results reveal a novel function for U2AF35, a critical role for the 3' splice site AG at the earliest steps of spliceosome assembly and the need for a weakened U2AF35-AG interaction to regulate intron removal.

Adenine Nucleotides↗
PubMed1999

Long-term results after thromboendarterectomy for chronic pulmonary embolism.

OBJECTIVE: In patients with chronic thromboembolic pulmonary hypertension, pulmonary vascular resistance (PVR) can be reduced by pulmonary thromboendarterectomy (PTE). In this study, long-term symptomatic and hemodynamic effects were investigated. METHODS: Twenty-two patients (12 female, 10 male, mean age 40 years, preoperative NYHA functional class II/III/IV: n = 1/12/9) were re-evaluated 48-72 months (mean 60 months) after surgery. In addition to clinical assessment, radiologic, hemodynamic and echocardiographic investigations were performed. RESULTS: All patients reported a marked improvement of their clinical condition. At follow-up, 11 patients were identified as NYHA class I, 10 as NYHA class II and one patient was in class III. PVR and mean pulmonary artery pressure (mPAP) were significantly reduced (preoperative PVR 800+/-274 dynes/s per cm(-5), follow-up PVR 180+/-28.3 dynes/s per cm(-5); P < 0.001; preoperative mPAP 48.5+/-7.4 mmHg, follow-up mPAP 27.5+/-4.9 mmHg; P < 0.001). There was also a significant increase in arterial blood oxygen tension (preoperative PaO2 59+/-10 mmHg; follow-up PaO2 84+/-12 mmHg; P < 0.001). Chest roentgenograms and echocardiographic examinations revealed significantly decreased right heart dimensions and a recovery of right heart function. CONCLUSION: In patients with severe chronic thromboembolic pulmonary hypertension, persistent symptomatic and hemodynamic improvements can be achieved by PTE.

Adult↗
PubMed1999

Evidence for substrate-specific requirement of the splicing factor U2AF(35) and for its function after polypyrimidine tract recognition by U2AF(65).

U2 snRNP auxiliary factor (U2AF) promotes U2 snRNP binding to pre-mRNAs and consists of two subunits of 65 and 35 kDa, U2AF(65) and U2AF(35). U2AF(65) binds to the polypyrimidine (Py) tract upstream from the 3' splice site and plays a key role in assisting U2 snRNP recruitment. It has been proposed that U2AF(35) facilitates U2AF(65) binding through a network of protein-protein interactions with other splicing factors, but the requirement and function of U2AF(35) remain controversial. Here we show that recombinant U2AF(65) is sufficient to activate the splicing of two constitutively spliced pre-mRNAs in extracts that were chromatographically depleted of U2AF. In contrast, U2AF(65), U2AF(35), and the interaction between them are required for splicing of an immunoglobulin micro; pre-RNA containing an intron with a weak Py tract and a purine-rich exonic splicing enhancer. Remarkably, splicing activation by U2AF(35) occurs without changes in U2AF(65) cross-linking to the Py tract. These results reveal substrate-specific requirements for U2AF(35) and a novel function for this factor in pre-mRNA splicing.

Animals↗
PubMed1999

A Scj1p homolog and folding catalysts present in dog pancreas microsomes.

Dog pancreas microsomes represent the key components of the established model system for the analysis of protein transport into the mammalian endoplasmic reticulum. More recently, these microsomes were also employed in cell-free systems which address questions related to protein folding and protein degradation in the mammalian endoplasmic reticulum. In order to get at a complete picture of these undoubtedly related processes in the in vitro system we need to know all the proteins we are dealing with, and their respective stoichiometries. Here we give a progress report on our attempts to identify and to quantify the soluble molecular chaperones and folding catalysts which are present in the lumen of dog pancreas microsomes. Eventually, we will need to know how the in vitro system compares with the situation in intact pancreatic cells as well as in other cells.

Amino Acid Sequence↗
PubMed1998

Male fights of hamadryas baboons

An attempt is made to develop a model of male fights which can account for the stylized facts, observed by Kummer and his team, for hamadryas baboons. By two special versions of the general model it is shown that these observations can be consistently explained by one mathematical model which may deserve some interest for its own sake. To demonstrate the relative advantages of our approach we also analyse an ad hoc-type of model.Copyright 1998 Academic Press Limited Copyright 1998 Academic Press Limited

Journal Article↗
PubMed1998

Small leiomyosarcoma of the renal capsule: CT findings.

Three unusual cases of small-size leiomyosarcoma of the perirenal space were studied with CT. The renal capsule has been proved to be the origin of this type of tumor. A CT examination is accurate in suggesting the site of origin and excluding a renal cell carcinoma. However, unless evidence of invasion is noted, it is impossible on CT features to discriminate leiomyosarcoma from a benign leiomyoma.

Adult↗