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Biomedical subjects

R Ulrich

Publications and source records attributed to R Ulrich.

At least 55 records · Page 3Linked to original sources

Preparation of response force and movement direction: onset effects on the lateralized readiness potential.

Two experiments assessed the preparatory effects of advance information about response force and movement direction on the lateralized readiness potential (LRP). In a choice reaction time (RT) task, an imperative stimulus required an isometric flexion or an extension of the left or right index finger. Prior information about response force or about movement direction reduced RT and shortened the interval from the onset of the imperative stimulus up to the onset of the LRP. Advance information, however, about direction but not about force decreased the interval from LRP onset to the onset of the overt response. The identical pattern of results was obtained in a second experiment, in which each participant performed both precue conditions. The findings of both experiments support the notion that response force is specified before movement direction. These results are consistent with the view accordingly different mechanisms are involved in the specification of muscle force and movement direction.

Adult↗

New chimaeric hepatitis B virus core particles carrying hantavirus (serotype Puumala) epitopes: immunogenicity and protection against virus challenge.

Virus-like particles generated by the heterologous expression of virus structural proteins are able to potentiate the immunogenicity of foreign epitopes presented on their surface. In recent years epitopes of various origin have been inserted into the core antigen of hepatitis B virus (HBV) allowing the formation of chimaeric HBV core particles. Chimaeric core particles carrying the 45 N-terminal amino acids of the Puumala hantavirus nucleocapsid protein induced protective immunity in bank voles, the natural host of this hantavirus. Particles applied in the absence of adjuvant are still immunogenic and partially protective in bank voles. Although a C-terminally truncated core antigen of HBV (HBcAg delta) tolerates the insertion of extended foreign sequences, for the construction of multivalent vaccines the limited insertion capacity is still a critical factor. Recently, we have described a new system for generating HBV 'mosaic particles' in an Escherichia coli suppressor strain based on a readthrough mechanism on a stop linker located in front of the insert. Those mosaic particles are built up by both HBcAg delta and the HBcAg delta/Puumala nucleocapsid readthrough protein. The particles formed presented the 114 amino acid (aa) long hantavirus sequence, at least in part, on their surface and induced antibodies against the hantavirus sequence in bank voles. Variants of the stop linker still allowed the formation of mosaic particles demonstrating that stop codon suppression alone is sufficient for the packaging of longer foreign sequences in mosaic particles. Another approach to increase the insertion capacity is based on the simultaneous insertion of different Puumala nucleocapsid protein sequences (aa 1-45 and aa 75-119) into two different positions (aa 78 and behind aa 144) of a single HBcAg molecule. The data presented are of high relevance for the generation of multivalent vaccines requiring a high insertion capacity for foreign sequences.

Amino Acid Sequence↗

Capsid protein-encoding genes of hamster polyomavirus and properties of the viral capsid.

On the basis of its genome organization the hamster polyomavirus (HaPV) is closely related to the murine polyomavirus Py. But HaPV infection, in contrast to Py infection, gives rise to two different tumor types; depending on the hamster strain used for infection, HaPV induces either epitheliomas or lymphomas. Although the HaPV virions were shown to be similar to those of Py and SV40, more precise information about the structure and protein composition of the HaPV capsid was still missing. Here we describe the primary structure of the capsid protein-encoding HaPV genes and the structure and protein composition of the HaPV capsid. Virions isolated from epitheliomas in HaPV-infected hamsters were shown by electron microscopy to be spherical particles with the typical icosahedral structure of polyomaviruses. However, in contrast to the capsids of SV40 and Py, a T = 7 laevo symmetry of HaPV capsids was observed. Separation of HaPV virions in SDS polyacrylamide gels and Western blotting with VP1-specific antisera identified VP1 as the major capsid protein species corresponding in its molecular weight to the predicted value of 41.8 kDa. Because of the presence of two potential translational initiation sites in the VP1 gene, the N-terminal amino acid sequence of virion VP1 was determined and found to start at the second initiation site. The amino acid homologies of HaPV capsid proteins shared with Py varied between 65.5% (VP1), 45.4% (VP3) and 44.6% (VP2), whereas the homologies to the relevant proteins of other polyomaviruses were found to range between 49.6-57.9% for VP1 and 28.9-41% for VP2/VP3.

Amino Acid Sequence↗

Characterization of potential insertion sites in the core antigen of hepatitis B virus by the use of a short-sized model epitope.

Core particles of hepatitis B virus (HBV) are able to improve the immunogenicity of foreign sequences exposed on the particle surface. The insertion site in the core antigen of HBV (HBcAg) determines the surface presentation and thus the immunogenicity of the foreign sequence. For direct comparison of the value of potential insertion sites in the core antigen, we constructed vectors allowing insertions of a model marker epitope DPAFR. This epitope was inserted at the N-terminus, the c/e1 loop, behind amino acid (aa) 144 and behind aa 183 (DPAF only). In addition, we generated a mosaic construct allowing the co-expression of HBcAg and a HBcAg/DPAFR fusion protein due to a suppressor tRNA-mediated readthrough mechanism. All 6 constructs allowed the formation of chimaeric or mosaic core-like particles. Western blot analyses and a direct ELISA demonstrated the presence of the DPAFR sequence in the chimaeric and mosaic particles. Competitive ELISA and immune electron-microscopic data suggested the c/e1 loop as the insertion site of choice for presenting foreign sequences on the surface of chimaeric HBV core particles. However, the N-terminal fusion also allowed partial surface exposure of the DPAFR motif. In contrast, in particles of constructs carrying the DPAFR insert at aa position 144 or 183, respectively, the epitope seemed not to be surface accessible.

Blotting, Western↗

HBV core particles allow the insertion and surface exposure of the entire potentially protective region of Puumala hantavirus nucleocapsid protein.

Core particles of the hepatitis B virus (HBV) potentiate the immune response against foreign epitopes presented on their surface. Potential insertion sites in the monomeric subunit of the HBV core protein were previously identified at the N- and C-terminus and in the immunodominant c/e1 region. In a C-terminally truncated core protein these sites were used to introduce the entire 120 amino acid (aa)-long potentially immunoprotective region of the hantavirus (serotype Puumala) nucleocapsid protein. The N- and C-terminal fusion products were unable to form core-like particles in detectable amounts. However, a suppressable stop codon located between the HBV core and the C-terminally fused hantavirus sequence restored the ability to form particles ('mosaic particles'); in contrast to the C-terminal fusion product the mosaic construct allowed the formation of particles built up by the core protein itself and the HBV core-Puumala nucleocapsid-readthrough protein. The mosaic particles exposed the 120 aa region of the PUU nucleocapsid protein on their surface as demonstrated by ELISA and immuno electron microscopy applying different monoclonal antibodies. Insertion of the hantaviral sequence into the c/e1 region not only allowed the formation of chimeric particles, but again the surface accessibility of the sequence. HBV core antigenicity itself was, however, reduced in the particles carrying insertions in the c/e1 region, probably due to a masking effect of the 120 aa long insert.

Animals↗

Yeast cells allow high-level expression and formation of polyomavirus-like particles.

Polyomavirus-derived virus-like particles (VLPs) have been described as potential carriers for encapsidation of nucleic acids in gene therapy. Although VLPs can be generated in E. coli or insect cells, the yeast expression system should be advantageous as it is well established for the biotechnological generation of products for human use, especially because they are free of toxins hazardous for humans. We selected the yeast Saccharomyces cerevisiae for expression of the major capsid protein VP1 of a non-human polyomavirus, the hamster polyomavirus (HaPV). Two entire HaPV VP1-coding sequences, starting with the authentic and a second upstream ATG, respectively, were subcloned and expressed to high levels in Saccharomyces cerevisiae. The expressed VP1 assembled spontaneously into VLPs with a structure resembling that of the native HaPV capsid. Determination of the subcellular localization revealed a nuclear localization of some particles formed by the N-terminally extended VP1, whereas particles formed by the authentic VP1 were found mainly in the cytoplasmic compartment.

Animals↗

The surface-weight illusion: on the contribution of grip force to perceived heaviness.

Previous psychophysical studies have shown that an object, lifted with a precision grip, is perceived as being heavier when its surface is smooth than when it is rough. Three experiments were conducted to assess whether this surface-weight illusion increases with object weight, as a simple fusion model suggests. Experiment 1 verified that grip force increases more steeply with object weight for smooth objects than for rough ones. In Experiment 2, subjects rated the weight of smooth and rough objects. Smooth objects were judged to be heavier than rough ones; however, this effect did not increase with object weight. Experiment 3 employed a different psychophysical method and replicated this additive effect, which argues strongly against the simple fusion model. The whole pattern of results is consistent with a weighted fusion model in which the sensation of grip force contributes only partially to the perceived heaviness of a lifted object.

Adult↗

Effects of auditory stimulus intensity on response force in simple, go/no-go, and choice RT tasks.

In four experiments, increasing the intensities of both relevant and irrelevant auditory stimuli was found to increase response force (RF) in simple, go/no-go, and choice reaction time (RT) tasks. These results raise problems for models that localize the effects of auditory intensity on purely perceptual processes, indicating instead that intensity also affects motor output processes under many circumstances. In Experiment 1, simple RT, go/no-go, and choice RT tasks were compared, using the same stimuli for all tasks. Auditory stimulus intensity affected both RT and RF, and these effects were not modulated by task. In Experiments 2-4, an irrelevant auditory accessory stimulus accompanied a relevant visual stimulus, and the go/no-go and choice tasks were used. The intensity of the irrelevant auditory accessory stimulus was found to affect RT and RF, although the sizes of these effects depended somewhat on the temporal predictability of the accessory stimulus.

Adult↗

Short report: simultaneous occurrence of Dobrava, Puumala, and Tula Hantaviruses in Slovakia.

The prevalence of antibody to hantaviruses in Slovakia (serum panel n = 2,133) was lower in the western part (0.54%) and higher in the eastern part (1.91%) of the country and was found to be significantly enhanced in a group of forest workers from eastern Slovakia (5.88%). One-third of the IgM-negative convalescent phase sera from patients with hemorrhagic fever with renal syndrome exhibited antibodies reacting predominantly with Puumala virus antigen, while two-thirds had antibodies directed mainly against Hantaan virus antigen. Fine analysis of two Hantaan virus-reactive sera by a focus reduction neutralization test showed that Dobrava hantavirus was the source of these human infections. Initial results of rodent screening indicated the circulation of Dobrava virus in populations of striped field mice (Apodemus agrarius) in eastern Slovakia.

Animals↗

[Intersensory facilitation: also concomitant visual stimuli can decrease reaction time].

Subjects respond faster to a visual response signal when an auditory accessory is presented at the same time. In contrast, a visual accessory does not reduce reaction time to an auditory response signal. Previous studies suggest that this asymmetrical effect is due to different properties of visual and auditory accessories (i.e., arousal and preparation enhancement). We assessed whether this asymmetrical effect would disappear when subjects were to process the accessory stimulus in a secondary task while responding to the response signal in the main task. This dual task method formed the basis for two experiments. Each experiment employed both visual and auditory accessories, as well as auditory and visual response signals. Experiment 1 manipulated factorially the intensity levels of the accessory and response signal. Experiment 2 was similar to Experiment 1 but manipulated the time interval between the accessory and the response signal instead of stimulus intensities. Response force was recorded in addition to reaction time. In both experiments the previously reported asymmetrical effect disappeared showing that auditory and visual accessories are functionally equivalent when the task demands more central processing of these stimuli. The analysis of response force suggested that both the visual and auditory accessory produce nonspecific arousal effects that may facilitate the generation of the response.

Adult↗

Degradation of polychlorinated biphenyl mixtures by the lignin-degrading fungus Phanerochaete chrysosporium.

Degradation of lower-chlorinated and higher-chlorinated PCB congeners (Delor 103 and Delor 105 as equivalents of Aroclor 1242 and Aroclor 1254, respectively) by the white-rot fungus Phanerochoete chrysosporium was investigated in N-limited and non-limited media. No degradation of either Delor 103 or Delor 105 was found in a N-limited medium 9 d after their addition whereas in the non-limited medium during the same period their levels dropped by 55 and 58%, respectively. The degradation was non-specific and no significant differences in the degradation of di-, tri-, tetra-, penta-, hexa-, and hepta-congeners were found. No activity of Mn-dependent peroxidase (MnP) or lignin peroxidase (LiP) was detectable in the non-limited medium. We assume that the degradation of PCBs by P. chrysosporium is relatively non-specific, takes place under non-limited conditions and is independent of the activities of MnP or LiP.

Aroclors↗

Core particles of hepatitis B virus as carrier for foreign epitopes.

To be effective as vaccines, most monomeric proteins and peptides either require chemical coupling to high molecular weight carriers or application together with adjuvants. More recently, recombinant DNA techniques have been used to insert foreign epitopes into proteins with inherent multimerization capacity, such as particle-forming viral capsid or envelope proteins. The core protein of hepatitis B virus (HBcAg), because of its unique structural and immunological properties, has gained widespread interest as a potential antigen carrier. Foreign sequences of up to approximately 40 amino acid residues at the N terminus, 50 or 100 amino acids in the central immunodominant c/e 1 epitope region of HBcAg, and up to 100 or even more residues at the C terminus, did not interfere with particle formation. The humoral immunogenicity of inserted epitopes is determined by the immunogenicity of the peptide itself and its surface exposure, and is influenced by the route of application. The probably flexible and surface-exposed c/e1 region emerged as the most promising insertion site. When applied together with adjuvants approved for human and veterinary use, or even without adjuvants, such chimeric particles induced B and T cell immune responses against the inserted epitopes. In some cases neutralizing antibodies, cytotoxic T cells and protection against challenge with the intact pathogen were demonstrated. Major factors for the potentiated immune response against the foreign epitopes are the multimeric structure of chimeric HBcAg that results in a high epitope density per particle, and the provision of T cell help by the carrier moiety. Beyond its use as subunit vaccine, chimeric HBcAg produced in attenuated Salmonella strains may be applicable as live vaccine.

Epitopes↗

Effects of chronic exposure to PCBs on cytochrome P450 systems and steroidogenesis in liver and testis of bulls (Bos taurus).

Effects of chronic exposure to PCBs on the microsomal cytochrome P450 (CYP) enzymes in liver and testis of bulls (Bos taurus) were determined by comparing the constitutive and PCB-induced alkoxyresorufin O-dealkylase and testosterone hydroxylase activities. Specific inductions of the prevailing hepatic ethoxyresorufin O-deethylation and 6 beta-hydroxylation of testosterone are suggestive of the induction of CYP1A1 and CYP3A-like enzymes by PCBs. A high level of PCB-inducible androstenedione formation was also found. The hepatic CYP2B activities (i.e. pentoxyresorufin O-depentylase and testosterone 16 beta-hydroxylase) and CYP2C11-like testosterone 2 alpha-hydroxylase were increased only weakly. The testicular microsomal CYP activities were non-specifically reduced by the PCB exposure, except for the androstenedione formation and 16 beta-hydroxylation of testosterone. The inhibition of the activity of mitochondrial CYP11A, as the rate-limiting enzyme of steroidogenesis measured with resorufin 3 beta-hydroxy-22,23-bisnor-5-cholenyl ether as the fluorogenic substrate, exceeded 50% in testes of the PCB-contaminated bulls. The latter activity as well as the hepatic testosterone 6 beta-hydroxylation and hepatic and testicular androstenedione formation may significantly contribute to the decrease in testosterone levels after the PCB intake.

Animals↗

Effects of stimulus duration and intensity on simple reaction time and response force.

Previous research indicates that response force increases with stimulus intensity in simple reaction time (SRT) tasks. This result contradicts the common view that the perceptual system activates the motor system via a punctate go signal of fixed size. An elaborated view assumes that the size of the go signal depends on stimulus intensity so that more intense stimuli yield more forceful responses. In order to examine the latter hypothesis, the present experiments manipulated stimulus duration as well as intensity. Response force increased with duration even beyond a critical value of about 60 ms at which stimulus duration no longer affected SRT. In addition, increasing the duration of a stimulus also increased the duration of force output. These findings argue against models with punctate transmission of activation to the motor system. Certain continuous models and variable output models with prolonged go signals provide acceptable accounts of these effects.

Acoustic Stimulation↗

Germany and its immigrants: a socio-demographic analysis.

"Germany is today, along with the USA and Russia, one of the three most important immigration countries worldwide. The authors examine how the immigrant population of Germany has risen despite the fact that the German government has sought to restrict it. They analyse six major streams of migration: refugees and expellees who came immediately after World War II, German resettlers from Eastern Europe (¿Aussiedler'), emigration of (West) Germans, migration between East and West Germany, foreign labour migrants and asylum seekers. The dynamics of immigration within each of these channels was remarkably different. As far as absorption and integration are concerned the authors argue that different groups of immigrants should be treated more equally."

Acculturation↗

Determinants of spontaneous extrapyramidal symptoms in elderly psychiatric inpatients diagnosed with Alzheimer's disease, major depressive disorder, or psychotic disorders.

Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.

Age Factors↗

Directed attention prolongs the perceived duration of a brief stimulus.

Stelmach, Herdman, and McNeil (1994) suggested recently that the perceived duration for attended stimuli is shorter than that for unattended ones. In contrast, the attenuation hypothesis (Thomas & Weaver, 1975) suggests the reverse relation between directed attention and perceived duration. We conducted six experiments to test the validity of the two contradictory hypotheses. In all the experiments, attention was directed to one of two possible stimulus sources. Experiments 1 and 2 employed stimulus durations from 70 to 270 msec. A stimulus appeared in either the visual or the auditory modality. Stimuli in the attended modality were rated as longer than stimuli in the unattended modality. Experiment 3 replicated this finding using a different psychophysical procedure. Experiments 4-6 showed that the finding applies not only to stimuli from different sensory modalities but also to stimuli appearing at different locations within the visual field. The results of all six experiments support the assumption that directed attention prolongs the perceived duration of a stimulus.

Adult↗