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S Wohlgemuth

Publications and source records attributed to S Wohlgemuth.

15 recordsLinked to original sources
PubMed2004

Variability of spike trains and the processing of temporal patterns of acoustic signals-problems, constraints, and solutions.

Object recognition and classification by sensory pathways is rooted in spike trains provided by sensory neurons. Nervous systems had to evolve mechanisms to extract information about relevant object properties, and to separate these from spurious features. In this review, problems caused by spike train variability and counterstrategies are exemplified for the processing of acoustic signals in orthopteran insects. Due to size limitations of their nervous system we expect to find solutions that are stripped to the computational basics. A key feature of auditory systems is temporal resolution, which is likely limited by spike train variability. Basic strategies to reduce such variability are to integrate over time, or to average across several neurons. The first strategy is constrained by its possible interference with temporal resolution. Grasshoppers do not seem to explore temporal integration much, in spite of the repetitive structure of their songs, which invites for 'multiple looks' at the signal. The benefits of averaging across neurons depend on uncorrelated responses, a factor that may be crucial for the performance and evolution of small nervous systems. In spite of spike train variability the temporal information necessary for the recognition of conspecifics is preserved to a remarkable degree in the auditory pathway.

Acoustic Stimulation↗
PubMed2002

Distance estimation in the third dimension in desert ants.

Desert ants of the genus Cataglyphis perform large-scale foraging excursions from which they return to their nest by path integration. They do so by integrating courses steered and the distances travelled into a continually updated home vector. While it is known that the angular orientation is based on skylight cues, it still is largely enigmatic how the ants measure distances travelled. We extended the ants' task into the third dimension by training them to walk within an array of uphill and downhill channels, and later testing them on flat terrain, or vice versa. In these tests the ants indicated homing distances that did not correspond to the distances actually travelled, but to the ground distances; that is, to the sum of the horizontal projections of the uphill and downhill segments of the ants' paths. These results suggest a much more sophisticated mechanism of distance estimation than hitherto thought. The ants must be able to measure the slopes of undulating terrain and to integrate this information into their "odometer" for the distance estimation process.

Animals↗
PubMed2001

Ant odometry in the third dimension.

Desert ants (Cataglyphis) are renowned for their ability to perform large-scale foraging excursions and then return to the nest by path integration. They do so by integrating courses steered and the distances travelled into a continually updated home vector. Whereas the angular orientation is based on skylight cues, how the ants gauge the distances travelled has remained largely unclear. Furthermore, almost all studies on path integration in Cataglyphis, as well as in spiders, rodents, and humans, have aimed at understanding how the animals compute homebound courses in the horizontal plane. Here, we investigate for the first time how an animal's odometer operates when a path integration task has to be accomplished that includes a vertical component. We trained Cataglyphis ants within arrays of uphill and downhill channels, and later tested them on flat terrain, or vice versa. In all these cases, the ants indicated homing distances that corresponded not to the distances actually travelled but to the ground distances; that is, to the sum of the horizontal projections of the uphill and downhill segments of the ants' paths.

Africa, Northern↗
PubMed2001

Solution structure of the Ras binding domain of the protein kinase Byr2 from Schizosaccharomyces pombe.

BACKGROUND: After activation, small GTPases such as Ras transfer the incoming signal to effectors by specifically interacting with the binding domain of these proteins. Structural details of the binding domain of different effectors determine which pathway is predominantly activated. Byr2 from fission yeast is a functional homolog of Raf, which is the direct downstream target of Ras in mammalians that initiates a protein kinase cascade. The amino acid sequence of Byr2's Ras binding domain is only weakly related to that of Raf, and Byr2's three-dimensional structure is unknown. RESULTS: We have solved the 3D structure of the Ras binding domain of Byr2 (Byr2RBD) from Schizosaccharomyces pombe in solution. The structure consists of three alpha helices and a mixed five-stranded beta pleated sheet arranged in the topology betabetaalphabetabetaalphabetaalpha with the first seven canonic secondary structure elements forming a ubiquitin superfold. 15N-(1)H-TROSY-HSQC spectroscopy of the complex of Byr2RBD with Ras*Mg(2+)*GppNHp reveals that the first and second beta strands and the first alpha helix of Byr2 are mainly involved in the protein-protein interaction as observed in other Ras binding domains. Although the putative interaction site of H-Ras from human and Ras1 from S. pombe are identical in sequence, binding to Byr2 leads to small but significant differences in the NMR spectra, indicating a slightly different binding mode. CONCLUSIONS: The ubiquitin superfold appears to be the general structural motif for Ras binding domains even in cases with vanishing sequence identity. However, details of the 3D structure and the interacting interface are different, thereby determining the specifity of the recognition of Ras and Ras-related proteins.

Amino Acid Sequence↗
PubMed2001

The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast.

BACKGROUND: The small GTP binding protein Ras has important roles in cellular growth and differentiation. Mutant Ras is permanently active and contributes to cancer development. In its activated form, Ras interacts with effector proteins, frequently initiating a kinase cascade. In the lower eukaryotic Schizosaccharomyces pombe, Byr2 kinase represents a Ras target that in terms of signal-transduction hierarchy can be considered a homolog of mammalian Raf-kinase. The activation mechanism of protein kinases by Ras is not understood, and there is no detailed structural information about Ras binding domains (RBDs) in nonmammalian organisms. RESULTS: The crystal structure of the Ras-Byr2RBD complex at 3 A resolution shows a complex architecture similar to that observed in mammalian homologous systems, with an interprotein beta sheet stabilized by predominantly polar interactions between the interacting components. The C-terminal half of the Ras switch I region contains most of the contact anchors, while on the Byr2 side, a number of residues from topologically distinct regions are involved in complex stabilization. A C-terminal helical segment, which is not present in the known mammalian homologous systems and which is part of the auto-inhibitory region, has an additional binding site outside the switch I region. CONCLUSIONS: The structure of the Ras-Byr2 complex confirms the Ras binding module as a communication element mediating Ras-effector interactions; the Ras-Byr2 complex is also conserved in a lower eukaryotic system like yeast, which is in contrast to other small GTPase families. The extra helical segment might be involved in kinase activation.

Amino Acid Sequence↗
PubMed2000

Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin.

Mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin at effector region threonine 35 has diverse effects on the Ras GTPase cycle, the dominant one of which is the inhibition of Ras-Raf coupling, leading to complete blockade of Ras downstream signaling. To understand the structural basis of the functional consequences of glucosylation, the X-ray crystal structure of glucosylated Ras-GDP was compared with that of non-modified Ras. Glucosylated Ras exhibits a different crystal packing but the overall three-dimensional structure is not altered. The glucose group does not affect the conformation of the effector loop. Due to steric constraints, the glucose moiety prevents the formation of the GTP conformation of the effector loop, which is a prerequisite for binding to the Raf-kinase. The X-ray crystal data also revealed the alpha-anomeric configuration of the bound glucose, indicating that the glucose transfer proceeds under retention of the C-1 configuration of the d-alpha-glucose. Therefore, glucosylation preserves the inactive conformation of the effector loop independently of the nucleotide occupancy, leading to a complete inhibition of downstream signaling of Ras.

Bacterial Toxins↗
PubMed2000

Hot microscopic areas of iodine-deficient euthyroid goitres contain constitutively activating TSH receptor mutations.

Constitutively activating TSH receptor mutations have been established as the most common molecular basis for the pathogenesis of toxic thyroid nodules. These mutations result in uncontrolled signalling through the TSH receptor that is likely to cause hyperfunction and proliferation. The incidence of toxic multinodular goitres has been demonstrated to be related to iodine deficiency. Moreover, scintigraphically autonomous areas are found in 40% of euthyroid goitres from iodine-deficient areas. To investigate the molecular cause of these autonomous areas, small autoradiographically hot areas were examined for somatic TSH receptor mutations using archival tissue sections from 14 patients with euthyroid goitres, which had been originally prepared nearly 20 years ago. All patients had received (125)I 17 h preoperatively for the autoradiographic investigation of their thyroid. Areas with high and low (125)I-labelling on autoradiography sections were collected separately either from serial paraffin-embedded tissue sections, or Eukitt-embedded tissue sections containing the autoradiograph. After genomic DNA extraction, the transmembrane segment of the TSH receptor was PCR-amplified and directly sequenced. Somatic TSH receptor mutations were identified in areas with high (125)I-labelling in four patients: A623I, L629P, F631L, and T632I. This is the first evidence that TSH receptor mutations occur in microscopic areas with increased (125)I-labelling in euthyroid goiters and it suggests that TSH receptor mutations in these areas confer the potential to develop into toxic thyroid nodules. It is therefore very likely that toxic thyroid nodules originate from small autonomous areas in iodine-deficient euthyroid goitres that contain a TSH receptor mutation.

Female↗
PubMed2000

Lateral optic flow does not influence distance estimation in the desert ant Cataglyphis fortis.

The present account answers the question of whether desert ants (Cataglyphis fortis) gauge the distance they have travelled by using self-induced lateral optic-flow parameters, as has been described for bees. The ants were trained to run to a distant food source within a channel whose walls were covered with black-and-white gratings. From the food source, they were transferred to test channels of double or half the training width, and the distance they travelled before searching for home and their walking speeds were recorded. Since the animals experience different motion parallax cues when walking in the broader or narrower channels, the optic-flow hypothesis predicted that the ants would walk faster and further in the broader channels, but more slowly and less far in the narrower channels. In contrast to this expectation, neither the walking speeds nor the searching distances depended on the width or height of the channels or on the pattern wavelengths. Even when ventral-field visual cues were excluded by covering the eyes with light-tight paint, the ants were not influenced by lateral optic flow-field cues. Hence, walking desert ants do not depend on self-induced visual flow-field cues in gauging the distance they have travelled, as do flying honeybees, but can measure locomotor distance exclusively by idiothetic means.

Animals↗
PubMed2000

Intussusception after Roux-en-Y gastric bypass.

Intussusception is a common pediatric surgical problem. Its occurrence in adults is rare and usually involves a specific lead point such as a small bowel tumor or other mass. We describe two adults who developed intussusception after Roux-en-Y gastric bypass. Signs and symptoms of small bowel obstruction were seen in both of these patients, but the responsible pathology was unusual. Because of the increasing frequency with which these gastric bypass procedures are being performed, a high index of suspicion must be employed when dealing with these postoperative patients who present with abdominal complaints.

Adult↗
PubMed1999

Structural and biochemical analysis of Ras-effector signaling via RalGDS.

The structure of the complex of Ras with the Ras-binding domain of its effector RalGDS (RGS-RBD), the first genuine Ras-effector complex, has been solved by X-ray crystallography. As with the Rap-RafRBD complex (Nasser et al., 1995), the interaction is via an inter-protein beta-sheet between the switch I region of Ras and the second strand of the RGS-RBD sheet, but the details of the interactions in the interface are remarkably different. Mutational studies were performed to investigate the contribution of selected interface residues to the binding affinity. Gel filtration experiments show that the Ras x RGS-RBD complex is a monomer. The results are compared to a recently determined structure of a similar complex using a Ras mutant (Huang et al., 1998) and are discussed in relation to partial loss-of-function mutations and the specificity of Ras versus Rap binding.

Crystallography, X-Ray↗
PubMed1997

Structure of the Ras-binding domain of RalGEF and implications for Ras binding and signalling.

The solution structure of the Ras-binding domain (RBD) of Ral guanine-nucleotide exchange factor RalGEF was solved by NMR spectroscopy. The overall structure is similar to that of Raf-RBD, another effector of Ras, although the sequence identity is only 13%. 15N chemical shifts changes in the complex of RalGEF-RBD with Ras indicate an interaction similar to the intermolecular beta-sheet observed for the complex between Ras and Raf-RBD.

Amino Acid Sequence↗
PubMed1991

Isolation of a novel type-I fatty-acid synthetase from Euglena gracilis. Specific derepression in streptomycin-bleached cells.

A novel, high-molecular-mass fatty-acid synthetase (FAS) complex has been isolated from streptomycin-bleached Euglena gracilis cells. The enzyme was purified 250-fold from the crude cell homogenate and subsequently migrated upon SDS/PAGE as a single band of molecular mass 270 kDa. This apparent subunit size of the purified protein contrasted with a smaller size of only 200 kDa which was exhibited by the same protein upon immunoblotting of the crude cell extract. The purified Euglena FAS complex cosediments in a sucrose density gradient with yeast FAS and, from this, both enzymes were concluded to have the same overall molecular mass of 2.3 MDa. The enzyme described in this paper appears to be a typical type-I FAS multienzyme which clearly differs from the E. gracilis FAS so far described. Instead, it appears to be organized structurally similar to the type-I FAS multienzymes of lower fungi. In vitro, the purified Euglena FAS complex synthesizes mainly palmitic acid, or its CoA ester, from acetyl CoA and malonyl CoA as substrates. The Km values for acetyl CoA and malonyl CoA are 20 microM and 31 microM, respectively. Similar to the FAS enzymes of other lower eucaryotes, the Euglena type-I FAS is a flavoprotein. In contrast to yeast FAS, however, the flavin cofactor appears to be covalently attached to the enzyme protein. By immunological techniques, the enzyme was shown to be absent in green as well as in etiolated E. gracilis cells, while being rapidly induced upon streptomycin bleaching of heterotrophically growing green cells. The data suggest an inverse correlation between organellar development and derepression of this FAS complex.

Animals↗
PubMed1990

Scar endometriosis.

Scar endometriosis is a rare entity most commonly seen after surgical treatment of the uterus or fallopian tubes. We report three additional instances of scar endometriosis after cesarean sections as well as a patient who had synchronous scar endometriomas at separate surgical sites.

Adult↗
PubMedDate not supplied

Early experience utilizing the in situ saphenous vein technique in 54 patients.

We have compared our early and late experience utilizing in situ saphenous vein bypass graft for lower extremity arterial occlusive disease in 54 patients who underwent in situ femoral to popliteal and distal bypass grafts between July of 1983 and February 1985. There were 3 femoral to above-knee popliteal bypasses, 27 femoral to below-knee popliteal bypass grafts, 12 femoral to anterior tibial dorsalis pedis bypass grafts, 10 femoral to posterior tibial bypass grafts and 2 femoral to peroneal in situ bypass grafts. The operative indications were progressive disabling claudication in 8 (15%) and limb salvage in 46 (85%). Eighty-nine percent of the limb salvage patients had 0-1 vessel runoff by arteriogram. Cumulative life table patency of the 54 in situ bypass grafts was 79% at 20 months. One hundred percent of the patients who were operated on for disabling claudication had patent grafts at 20 months. Seventy-eight percent of the limb salvage patients had patent grafts. Fourteen of the limb salvage patients required amputation and of these 14, 10 had patent grafts at the time of amputation. There were 8 deaths in the series. Our results demonstrate that a definite learning curve exists with this technique, however, once established, long-term patency and improved limb salvage statistics can be obtained.

Aged↗