Biomedical subjects

Michael Frese

Publications and source records attributed to Michael Frese.

14 recordsLinked to original sources

PubMed2006

Reducing the negative effects of emotion work in service occupations: emotional competence as a psychological resource.

Although emotion work and emotional competence focus on similar processes, there has been a lack of integration between the 2 concepts. Emotion work is the regulatory effort to express organizationally desired emotions, whereas emotional competence encompasses skills that focus on how people deal with and regulate their own affect and that of others. The general hypothesis of this study was that emotional competence can be regarded as an important personal resource in emotion work because it moderates the relationships between work characteristics, emotional dissonance, and outcome variables. Eighty-four service employees completed a questionnaire on their working conditions and their well-being. In addition, peer ratings for emotional competence were completed. The authors found that emotional competence moderated most of the proposed relationships between work characteristics and emotional dissonance, between emotional dissonance and outcome variables, and between work characteristics and outcome variables.

Adult↗

PubMed2005

Self-regulation in error management training: emotion control and metacognition as mediators of performance effects.

In error management training, participants are explicitly encouraged to make errors and learn from them. Error management training has frequently been shown to lead to better performance than conventional trainings that adopt an error avoidant approach. The present study investigated self-regulatory processes mediating this effect. Fifty-five volunteer students learned a computer program under 1 of 3 conditions: error avoidant training, error management training, or error management training supplemented with a metacognitive module. As predicted, both forms of error management training led to better transfer performance than did error avoidant training (d = 0.75). Mediation hypotheses were fully supported: Emotion control and metacognitive activity (from verbal protocols) mediated performance differences. These findings highlight the potential of promoting self-regulatory processing during training.

Adaptation, Psychological↗

PubMed2005

Organizational error management culture and its impact on performance: a two-study replication.

The authors argue that a high-organizational error management culture, conceptualized to include norms and common practices in organizations (e.g., communicating about errors, detecting, analyzing, and correcting errors quickly), is pivotal to the reduction of negative and the promotion of positive error consequences. Organizational error management culture was positively related to firm performance across 2 studies conducted in 2 different European countries. On the basis of quantitative and qualitative cross-sectional data from 65 Dutch organizations, Study 1 revealed that organizational error management culture was significantly correlated with both organizational goal achievement and an objective indicator of economic performance. This finding was confirmed in Study 2, using change-of-profitability data from 47 German organizations. The results suggest that organizations may want to introduce organizational error management as a way to boost firm performance.

Communication↗

PubMed2005

Dissecting the interferon-induced inhibition of hepatitis C virus replication by using a novel host cell line.

The Hepatitis C virus (HCV), a member of the family Flaviviridae, is a major cause of chronic liver disease. Patients are currently treated with alpha interferon (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, this treatment is ineffective in eliminating the virus in a large proportion of individuals. IFN-induced antiviral activities have been intensively studied in the HCV replicon system. It was found that both IFN-alpha and IFN-gamma inhibit HCV replicons, but the underlying mechanisms have not yet been identified. Of note is that nearly all of these studies were performed with the human hepatoma cell line Huh-7. Here, we report that genotypes 1b and 2a replicons also replicate in the human hepatoblastoma cell line HuH6. Similar to what has been described for Huh-7 cells, we observed that efficient HCV replication in HuH6 cells depends on the presence of cell culture-adaptive mutations and the permissiveness of the host cell. However, three major differences exist: in HuH6 cells, viral replication is (i) independent from ongoing cell proliferation, (ii) less sensitive to certain antiviral compounds, and (iii) highly resistant to IFN-gamma. The latter is not due to a general defect in IFN signaling, as IFN-gamma induces the nuclear translocation of signal transducer and activator of transcription 1 (STAT1), the enhanced transcription of several IFN-regulated genes, and the inhibition of unrelated viruses such as influenza A virus and Semliki Forest virus. Taken together, the results establish HuH6 replicon cells as a valuable tool for IFN studies and for the evaluation of antiviral compounds.

Antiviral Agents↗

PubMed2004

Novel insights into hepatitis C virus replication and persistence.

Hepatitis C virus (HCV) is a small enveloped RNA virus that belongs to the family Flaviviridae. A hallmark of HCV is its high propensity to establish a persistent infection that in many cases leads to chronic liver disease. Molecular studies of the virus became possible with the first successful cloning of its genome in 1989. Since then, the genomic organization has been delineated, and viral proteins have been studied in some detail. In 1999, an efficient cell culture system became available that recapitulates the intracellular part of the HCV life cycle, thereby allowing detailed molecular studies of various aspects of viral RNA replication and persistence. This chapter attempts to summarize the current state of knowledge in these most actively worked on fields of HCV research.

Genome, Viral↗

PubMed2004

Interferon type I gene expression in chronic hepatitis C.

Hepatitis C virus (HCV) frequently causes chronic liver disease. The cause of viral persistence might be an inappropriate type I interferon (IFN) induction. To analyze the host's IFN response in chronic hepatitis C, we measured the transcription level of type I IFN genes as well as type I IFN-regulated genes in liver tissue and corresponding blood samples from patients with chronic hepatitis C, nonviral liver diseases, and a suspected but later excluded liver disease. Competitive and real-time RT-PCR assays were used to quantify the messenger RNA (mRNA) levels of all known IFN-alpha, IFN-beta, and IFN-lambda genes and those of some IFN-regulated genes. We failed to detect any hepatic type I IFN mRNA induction, although liver tissue of chronic hepatitis C patients contained high numbers of some type I IFN-inducible effector mRNA molecules. Analysis of peripheral blood samples, however, showed a clear type I IFN induction. Parallel experiments employing HCV replicon cell lines revealed that replication of HCV RNA is not sufficient to induce any type I IFN nor to induce directly type I IFN-regulated genes such as MxA. In conclusion, our data provide evidence for the absence of an induction of type I IFN genes by HCV in the human liver and argue for a further development of type I IFN-based therapies.

Adolescent↗

PubMed2004

Alternative approaches for efficient inhibition of hepatitis C virus RNA replication by small interfering RNAs.

Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has recently been shown that HCV RNA replication is susceptible to small interfering RNAs (siRNAs), but the antiviral activity of siRNAs depends very much on their complementarity to the target sequence. Thus, the high degree of sequence diversity between different HCV genotypes and the rapid evolution of new quasispecies is a major problem in the development of siRNA-based gene therapies. For this study, we developed two alternative strategies to overcome these obstacles. In one approach, we used endoribonuclease-prepared siRNAs (esiRNAs) to simultaneously target multiple sites of the viral genome. We show that esiRNAs directed against various regions of the HCV coding sequence as well as the 5' nontranslated region (5' NTR) efficiently block the replication of subgenomic and genomic HCV replicons. In an alternative approach, we generated pseudotyped retroviruses encoding short hairpin RNAs (shRNAs). A total of 12 shRNAs, most of them targeting highly conserved sequence motifs within the 5' NTR or the early core coding region, were analyzed for their antiviral activities. After the transduction of Huh-7 cells containing a subgenomic HCV replicon, we found that all shRNAs targeting sequences in domain IV or nearby coding sequences blocked viral replication. In contrast, only one of seven shRNAs targeting sequences in domain II or III had a similar degree of antiviral activity, indicating that large sections of the NTRs are resistant to RNA interference. Moreover, we show that naive Huh-7 cells that stably expressed certain 5' NTR-specific shRNAs were largely resistant to a challenge with HCV replicons. These results demonstrate that the retroviral transduction of HCV-specific shRNAs provides a new possibility for antiviral intervention.

Antiviral Agents↗

PubMed2003

Mental fatigue and the control of cognitive processes: effects on perseveration and planning.

We tested whether behavioural manifestations of mental fatigue may be linked to compromised executive control, which refers to the ability to regulate perceptual and motor processes for goal-directed behaviour. In complex tasks, compromised executive control may become manifest as decreased flexibility and sub-optimal planning. In the study we use the Wisconsin Card Sorting Test (WCST) and the Tower of London (TOL), which respectively measure flexibility (e.g., perseverative errors) and planning. A simple memory task was used as a control measure. Fatigue was induced through working for 2 h on cognitively demanding tasks. The results showed that compared to a non-fatigued group, fatigued participants displayed more perseveration on the WCST and showed prolonged planning time on the TOL. Fatigue did not affect performance on the simple memory task. These findings indicate compromised executive control under fatigue, which may explain the typical errors and sub-optimal performance that are often found in fatigued people.

Adult↗

PubMed2003

Hepatitis C virus RNA replication is resistant to tumour necrosis factor-alpha.

It was demonstrated using self-replicating hepatitis C virus (HCV) RNAs that both types of interferons (IFNs) (in particular IFN-alpha and IFN-gamma) are potent inhibitors of HCV replication in Huh-7 cells. Because IFN-gamma and tumour necrosis factor (TNF)-alpha trigger a partially overlapping set of antiviral defence mechanisms, it is tempting to speculate that TNF-alpha also inhibits HCV replication. However, this study shows that TNF-alpha does not affect HCV protein and RNA synthesis, nor does it synergistically enhance the inhibitory effect of IFN-gamma. Taken together, these results demonstrate that HCV replication in Huh-7 cells is highly resistant to TNF-alpha. It is, therefore, unlikely that the increased production of TNF-alpha, which is seen in many hepatitis C patients, contributes to HCV clearance by inducing antiviral defence mechanisms in infected hepatocytes.

Antiviral Agents↗

PubMed2003

The impact of mental fatigue on exploration in a complex computer task: rigidity and loss of systematic strategies.

We investigated the impact of mental fatigue on exploration in a complex computer task. The exploration behavior of participants who underwent a fatigue manipulation (N = 36) was compared with that of a control (nonfatigued) group (N = 32). A distinction was also made between participants with high or low levels of general computer experience. Results showed that fatigued participants used significantly less systematic exploration and made more errors than did nonfatigued participants. Fatigued participants with low computer experience also showed significantly more rigid behavior than did the other participants. No differences were found on the number of subtasks solved. Compared with low-experience participants, highly experienced participants showed significantly more systematic exploration, less unsystematic trial and error, solved more subtasks, and made fewer errors (marginally significant p = .056). Findings were interpreted as the result of reduced task engagement under fatigue and reduced involvement of executive control on behavior. Actual or potential applications of this research include guidelines to prevent detrimental effects of mental fatigue on exploration behavior.

Adult↗

PubMed2002

Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs.

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All treatments known so far rely on the antiviral activity of interferon alfa (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, only a fraction of the patients clear the virus during therapy and for those who do not respond there is currently no alternative treatment. Selectable subgenomic HCV RNAs (replicons) have been recently used to investigate the effect of IFN-alpha on HCV replication. However, it has not yet been analyzed whether other cytokines also play a role in the innate immune response against HCV. Here we show that IFN-gamma inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons. We further show that the inhibitory action of IFN-gamma does not rely on the production of nitric oxide or the depletion of tryptophan. In conclusion, our results suggest that cytotoxic T cells and natural killer cells may contribute to HCV clearance not only by cell killing but also by producing IFN-gamma, thereby enhancing the intracellular inhibition of viral replication.

Hepacivirus↗

PubMed2002

Hantaan virus infection causes an acute neurological disease that is fatal in adult laboratory mice.

Hantaan virus, the etiological agent of Korean hemorrhagic fever, is transmitted to humans from persistently infected mice (Apodemus agrarius), which serve as the primary reservoir. Here we demonstrate that several strains of adult Mus musculus domesticus (C57BL/6, BALB/c, AKR/J, and SJL/J) were susceptible to Hantaan virus infection when infected intraperitoneally. First clinical signs were loss of weight, ruffled fur, and reduced activity, which were followed by neurological symptoms, such as paralyses and convulsions. Within 2 days of disease onset, the animals died of acute encephalitis. PCR analysis indicated a systemic infection with viral RNA present in all major organs. Immunohistochemical and in situ hybridization analyses of postmortem material detected viral antigen and RNA in the central nervous system (predominantly brain), liver, and spleen. In the central nervous system, viral antigen and RNA colocalized with perivascular infiltrations, the predominant pathological finding. To investigate the involvement of the interferon system in Hantaan virus pathogenesis, we infected alpha/beta interferon receptor knockout mice. These animals were more susceptible to Hantaan virus infection, indicating an important role of interferon-induced antiviral defense mechanisms in Hantaan virus pathogenesis. The present model may help to overcome shortcomings in the development of therapeutic and prophylactic measurements against hantavirus infections.

Acute Disease↗

PubMed2001

Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway.

Hepatitis C virus (HCV) persists in the majority of infected individuals and is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is currently treated with interferon (IFN)-alpha or with a combination of IFN-alpha and ribavirin. The availability of an HCV replicon system (Lohmann et al., SCIENCE: 285, 110-113, 1999) allowed the investigation of the effects of IFN on genuine HCV replication in cultured cells. It is shown here that IFN-alpha inhibits subgenomic HCV RNA replication in HuH-7 human hepatoma cells. Immunofluorescence, Western blot and Northern blot analysis revealed that levels of both HCV protein and replicon RNA were reduced after treatment with IFN-alpha in a dose-dependent manner. In further experiments, it was investigated whether MxA plays a role in the inhibition of HCV. The human MxA protein is an IFN-induced GTPase that has antiviral activity against various RNA viruses. However, HCV RNA replication was not affected in transfected HuH-7 cells that transiently overexpressed MxA. Moreover, a dominant-negative mutant of MxA did not interfere with the antiviral activity of IFN-alpha against HCV RNA replication. Taken together, these results demonstrate that IFN-alpha inhibits HCV replicons via an MxA-independent pathway.

Antiviral Agents↗

PubMed2000

Resistance to Rift Valley fever virus in Rattus norvegicus: genetic variability within certain 'inbred' strains.

Rift Valley fever virus (RVFV) is the causative agent of Rift Valley fever, a widespread disease of domestic animals and humans in sub-Saharan Africa. Laboratory rats have frequently been used as an animal model for studying the pathogenesis of Rift Valley fever. It is shown here that Lewis rats (LEW/mol) are susceptible to infection with RVFV, whereas Wistar-Furth (WF/mol) rats are resistant to RVFV infection. LEW/mol rats developed acute hepatitis and died after infection with RVFV strain ZH548, whereas WF/mol rats survived the infection. Cross-breeding of resistant WF/mol rats with susceptible LEW/mol rats demonstrated that resistance is segregated as a single dominant gene. Primary hepatocytes but not glial cells from WF/mol rats showed the resistant phenotype in cell culture, indicating that resistance was cell type-specific. Moreover, when cultured hepatocytes were stimulated with interferon (IFN) type I there was no indication of a regulatory role of IFN in the RVFV-resistance gene expression in WF/mol rats. Interestingly, previous reports have shown that LEW rats from a different breeding stock (LEW/mai) are resistant to RVFV infections, whereas WF/mai rats are susceptible. Thus, inbred rat strains seem to differ in virus susceptibility depending on their breeding histories. A better genetic characterization of inbred rat strains and a revision in nomenclature is needed to improve animal experimentation in the future.

Animals↗