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J Scheller

Publications and source records attributed to J Scheller.

18 recordsLinked to original sources

The step response: a method to characterize mechanisms of renal blood flow autoregulation.

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow (RBF) is mediated by the rapid myogenic response, by the slower tubuloglomerular feedback (TGF) mechanism, and, possibly, by an even slower third mechanism. To evaluate the individual contribution of these mechanisms to RBF autoregulation, we analyzed the response of RBF to a step increase in RPP. In anesthetized rats, the suprarenal aorta was occluded for 30 s, and then the occlusion was released to induce a step increase in RPP. Three dampened oscillations were observed; their oscillation periods ranged from 9.5 to 13 s, from 34.2 to 38.6 s, and from 100.5 to 132.2 s, respectively. The two faster oscillations correspond with previously reported data on the myogenic mechanism and the TGF. In accordance, after furosemide, the amplitude of the intermediate oscillation was significantly reduced. Inhibition of nitric oxide synthesis by Nomega-nitro-l-arginine methyl ester significantly increased the amplitude of the 10-s oscillation. It is concluded that the parameters of the dampened oscillations induced by the step increase in RPP reflect properties of autoregulatory mechanisms. The oscillation period characterizes the individual mechanism, the dampening is a measure for the stability of the regulation, and the square of the amplitudes characterizes the power of the respective mechanism. In addition to the myogenic response and the TGF, a third rather slow mechanism of RBF autoregulation exists.

Animals↗

Transcription of mutS- and mutL-homologous genes during meiosis in Saccharomyces cerevisiae and identification of a regulatory cis-element for meiotic induction of MSH2.

We have analysed the levels of mRNA transcripts of the mutS- and mutL-homologous genes of the yeast Saccharomyces cerevisiae during the course of meiosis, by quantitative RT-PCR. We found that all mutS homologues (MSH1-6) were induced during meiosis, whereas no evidence for regulation of the mutL homologues (PMS1, MLH1-3) was obtained. Temporal expression patterns indicative of co-regulation were observed for the gene pairs MSH4/MSH5 and MSH2/ SPO11. Sequence comparisons of the 5' flanking regions revealed similar sequence stretches in the respective gene pairs, which may constitute regulatory elements. Similar sequences were also found in the 5' flanking regions of the pairs MSH1/MSH3 and MSH1/MSH6. Upstream of MSH2 three closely spaced sequences similar to UASH elements were found, which - surprisingly are located within the coding region of SPO21. Deletion of these elements resulted in loss of meiotic induction of MSH2. Genetic analysis of homozygous deletion mutants did not reveal any differences from wild type with respect to genetic distance estimates, aberrant segregation, or suppression of homoeologus recombination in an interspecies cross with Saccharomyces paradoxus.

Adenosine Triphosphatases↗

Production of spider silk proteins in tobacco and potato.

Spider dragline silk is a proteinaceous fiber with remarkable mechanical properties that make it attractive for technical applications. Unfortunately, the material cannot be obtained in large quantities from spiders. We have therefore generated transgenic tobacco and potato plants that express remarkable amounts of recombinant Nephila clavipes dragline proteins. Using a gene synthesis approach, the recombinant proteins exhibit homologies of >90% compared to their native models. Here, we demonstrate the accumulation of recombinant silk proteins, which are encoded by synthetic genes of 420-3,600 base pairs, up to a level of at least 2% of total soluble protein in the endoplasmic reticulum (ER) of tobacco and potato leaves and potato tubers, respectively. Using the present expression system, spider silk proteins up to 100 kDa could be detected in plant tissues. When produced in plants, the recombinant spidroins exhibit extreme heat stability-a property that is used to purify the spidroins by a simple and efficient procedure.

Amino Acid Sequence↗

MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage.

We have characterized the MPH1 gene from Saccharomyces cerevisiae. mph1 mutants display a spontaneous mutator phenotype. Homologs were found in archaea and in the EST libraries of Drosophila, mouse, and man. Mph1 carries the signature motifs of the DEAH family of helicases. Selected motifs were shown to be necessary for MPH1 function by introducing missense mutations. Possible indirect effects on translation and splicing were excluded by demonstrating nuclear localization of the protein and splicing proficiency of the mutant. A mutation spectrum did not show any conspicuous deviations from wild type except for an underrepresentation of frameshift mutations. The mutator phenotype was dependent on REV3 and RAD6. The mutant was sensitive to MMS, EMS, 4-NQO, and camptothecin, but not to UV light and X rays. Epistasis analyses were carried out with representative mutants from various repair pathways (msh6, mag1, apn1, rad14, rad52, rad6, mms2, and rev3). No epistatic interactions were found, either for the spontaneous mutator phenotype or for MMS, EMS, and 4-NQO sensitivity. mph1 slightly increased the UV sensitivity of mms2, rad6, and rad14 mutants, but no effect on X-ray sensitivity was observed. These data suggest that MPH1 is not part of a hitherto known repair pathway. Possible functions are discussed.

Carrier Proteins↗

Analysis of in vivo correction of defined mismatches in the DNA mismatch repair mutants msh2, msh3 and msh6 of Saccharomyces cerevisiae.

We have analysed the correction of defined mismatches in wild-type and msh2, msh3, msh6 and msh3 msh6 mutants of Saccharomyces cerevisiae in two different yeast strain backgrounds by transformation with plasmid heteroduplex DNA constructs. Ten different base/base mismatches, two single-nucleotide loops and a 38-nucleotide loop were tested. Repair of all types of mismatches was severely impaired in msh2 and msh3 msh6 mutants. In msh6 mutants, repair efficiency of most base/base mismatches was reduced to a similar extent as in msh3 msh6 double mutants. G/T and A/C mismatches, however, displayed residual repair in msh6 mutants in one strain background, implying a role for Msh3p in recognition of base/base mismatches. Furthermore, the efficiency of repair of base/base mismatches was considerably reduced in msh3 mutants in one strain background, indicating a requirement for MSH3 for fully efficient mismatch correction. Also the efficiency of repair of the 38-nucleotide loop was reduced in msh3 mutants, and to a lesser extent in msh6 mutants. The single-nucleotide loop with an unpaired A was less efficiently repaired in msh3 mutants and that with an unpaired T was less efficiently corrected in msh6 mutants, indicating non-redundant functions for the two proteins in the recognition of single-nucleotide loops.

DNA Repair↗

Dyscalculia and dyslexia after right hemisphere injury in infancy.

OBJECTIVE: To use the findings from neuropsychological evaluation and functional magnetic resonance imaging (fMRI) to assess interhemispheric reorganization of function after early unilateral brain injury. DESIGN AND METHODS: The study focused on one case of early brain injury that resulted in both dyscalculia and dyslexia. Brain injury was studied using both structural and fMRI. Intellectual function was evaluated using the Wechsler Intelligence Scale for Children, Third Edition, while visuospatial skills were assessed using the Block Design subtest of the Wechsler Intelligence Scale for Children, Third Edition, and Judgment of Line Orientation subtest. The Selective Reminding Test and the Recurring Figures Test were used to evaluate memory and orientation; language and speech skills were evaluated using the Boston Naming Test, Controlled Oral Word Association, Gates-MacGinitie Reading Test, and color naming. Various methods were used to study arithmetic skills, including the Wide Range Achievement Test-Revised and the Peabody Individual Achievement Test. The control group for fMRI consisted of nine normal subjects. SETTING: Neuropsychological laboratory in primary care hospital. PATIENT: A 17-year-old boy who had sustained a closed head injury associated with a partially depressed, right parietal skull fracture, and right temporal hemorrhage in a motor vehicle crash at age 7 months (November 9, 1977). Subsequent social behavior was normal, but the patient had difficulty throughout school in mathematics and spelling and was characterized as having a "short attention span." INTERVENTION: None. MAIN OUTCOME MEASURES: Standardized tests of arithmetic and reading supplemented by an assessment of calculation and quantitative skills. While performing calculations, fMRI disclosed predominantly left hemisphere activation involving the frontal and posterior parietal regions, whereas this task produced bilateral activation of the supramarginal gyrus in seven of nine normal subjects. RESULTS: Neuropsychological findings confirmed the presence of dyscalculia and dyslexia despite normal intellectual functioning. Visuospatial skills ranged from the low normal to average level. The fMRI findings were consistent with early interhemispheric transfer of visuospatial skills normally committed to the right parietal area to the left parietal region. The patient's dyscalculia and reading ability raise a question of acquired left parietal dysfunction as a consequence of the competition between verbal and visuospatial functions for left hemisphere representation. CONCLUSION: Interhemispheric reorganization of function may be bidirectional rather than a feature unique to the left hemisphere substrate for language.

Adolescent↗

Phenothiazine effect on gastrointestinal tract function.

Clinical evidence indicates that phenothiazines, specifically chlorpromazine (CPZ), used extensively in the treatment of patients with mental and/or neurologic disorders produce an ileus characterized by pseudoobstruction with an extended barium transit time of eight to ten days. Postoperatively, these patients have a protracted ileus, lasting from ten to fourteen days. In our present study we investigated the mechanism of action by which phenothiazines block gastrointestinal tract function as well as the possible reversal of this effect by pharmacologic agents. Guinea pigs were injected intraperitoneally with CPZ at a dose of 30 mg/kg/day for five to seventeen days. This caused deleterious effects in the gastrointestinal tract, such as cessation of peristalsis of small intestine and colon, and marked distension of the cecum. In vitro pharmacologic studies were performed on the electrically stimulated longitudinal muscle-myenteric plexus of the guinea pigs. We found that phenothiazines interfered with the neuromuscular mechanism of the intestine, as exemplified by a lack of response to electrical current stimulation. The effect was protracted, lasting at least 24 hours. These effects were reversed by the administration of the anticholinesterase, physostigmine (PGM), provided the block was less than 80 per cent. The paralytic ileus produced was similar to that found in man.

Animals↗

[Twin labor].

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Adolescent↗