Breast cancer screening and its associating factors among hungarian women aged 45-65: a cross-sectional study based on the European health interview surveys from 2009 to 2019.

BACKGROUND: In 2020, globally 685,000 people died, and 2.3 million women were diagnosed with breast cancer. The main cause of cancer deaths among women is breast cancer, which account for 15.5% of all cancer deaths. Most of these could have been avoided with timely diagnosis. The aim of our study was to determine the proportion of breast screening participation in Hungary, and to identify possible factors that may influence breast screening attendance. METHODS: Our data were gathered from the cross-sectional European Health Interview Surveys conducted in Hungary in 2009, 2014, and 2019. In terms of categorical characteristics, Pearson's chi-square test was performed to evaluate the differences between people who have attended breast screening within two years and who have only attended more than two years ago. To determine the factors that may have an impact on the uptake of screening, generalized linear model with logit link function regarding binomial probability distribution was executed. RESULTS: The responses of 2626 women between the age 45-65 were included in our study. In 2009 85% (n=741), in 2014 90% (n=851) and in 2019 87% (n=699) of the respondents claimed to have ever attended a breast screening in their life. In 2009 68% (n=594), in 2014 66% (n=630) and in 2019 64% (n=515) said that they have taken part in breast screening within two years (p=0.331). From 2014 to 2019 (AOR=0.72 [0.57-0.89]) the chance of attending breast screening was decreasing. We observed that both secondary (AOR=1.97 [1.60-2.44]) and tertiary educational level (AOR=2.23 [1.67-3.00]), higher perceived income (AOR=1.54 [1.25-1.90]), and more frequent meeting with the doctor (AOR=1.77 [1.39-2.27]) and with the specialist (AOR=1.88 [1.54-2.28]) appeared as protective factors of breast screening attendance. CONCLUSIONS: Our results show that the lifetime prevalence of breast screening participation is high, however the recommended biennial rate is relatively low. To increase the participation rate, various initiatives would be needed, especially for women in identified risk groups, which are lower educational level, lower perceived income, and less frequent meeting with the doctor and with the specialist.

Comparison of hesitancy between COVID-19 and seasonal influenza vaccinations within the general Hungarian population: a cross-sectional study.

BACKGROUND: The willingness to get COVID-19 or seasonal influenza vaccines has not yet been thoroughly investigated together, thus, this study aims to explore this notion within the general adult population. METHODS: The responses of 840 Hungarian participants were analysed who took part in a nationwide computer-assisted telephone interviewing. During the survey questions concerning various demographic characteristics, perceived financial status, and willingness to get the two types of vaccines were asked. Descriptive statistics, comparative statistics and word co-occurrence network analysis were conducted. RESULTS: 48.2% of participants were willing to get a COVID-19 vaccine, while this ratio for the seasonal influenza was only 25.7%. The difference was significant. Regardless of how the participants were grouped, based on demographic data or perceived financial status, the significant difference always persisted. Being older than 59 years significantly increased the willingness to get both vaccines when compared to the middle-aged groups, but not when compared to the younger ones. Having higher education significantly elevated the acceptance of COVID-19 vaccination in comparison to secondary education. The willingness of getting any type of COVID-19 vaccine correlated with the willingness to get both influenza and COVID-19. Finally, those who were willing to get either vaccine coupled similar words together to describe their thoughts about a COVID-19 vaccination. CONCLUSION: The overall results show a clear preference for a COVID-19 vaccine and there are several similarities between the nature of willingness to get either type of vaccine.

Endogenous single-strand DNA breaks at RNA polymerase II promoters in Saccharomyces cerevisiae.

Molecular combing and gel electrophoretic studies revealed endogenous nicks with free 3'OH ends at ∼100 kb intervals in the genomic DNA (gDNA) of unperturbed and G1-synchronized Saccharomyces cerevisiae cells. Analysis of the distribution of endogenous nicks by Nick ChIP-chip indicated that these breaks accumulated at active RNA polymerase II (RNAP II) promoters, reminiscent of the promoter-proximal transient DNA breaks of higher eukaryotes. Similar periodicity of endogenous nicks was found within the ribosomal rDNA cluster, involving every ∼10th of the tandemly repeated 9.1 kb units of identical sequence. Nicks were mapped by Southern blotting to a few narrow regions within the affected units. Three of them were overlapping the RNAP II promoters, while the ARS-containing IGS2 region was spared of nicks. By using a highly sensitive reverse-Southwestern blot method to map free DNA ends with 3'OH, nicks were shown to be distinct from other known rDNA breaks and linked to the regulation of rDNA silencing. Nicks in rDNA and the rest of the genome were typically found at the ends of combed DNA molecules, occasionally together with R-loops, comprising a major pool of vulnerable sites that are connected with transcriptional regulation.

Investigating the knowledge of and public attitudes towards genetic testing within the Visegrad countries: a cross-sectional study.

BACKGROUND: Previous studies have investigated various factors that can determine the attitudes of the citizens considering genetic testing. However, none of them investigated how these attitudes may differ between the Visegrad countries. METHODS: In this cross-sectional study a questionnaire developed by Dutch researchers was translated and used in Hungary, Slovakia, Czechia and Poland. In each country 1000 adult citizens were asked on the topics of personal benefits regarding genetic tests, genetic determinism, and finally, the availability and usage of genetic testing. Multivariate robust regression model was created including several possible influencing factors (such as age, sex, education, marital status, religiousness, and having a genetic test within the nuclear family) to identify the possible differences between the four countries. RESULTS: The Hungarian citizens had the most positive opinion on the personal benefits of genetic testing followed by the Czech, Slovak and Polish. All differences were significant in this regard. Considering genetic determinism, the Slovak citizens had a significantly firmer belief in this issue compared to the Hungarians. No other significant differences were observed in this domain. On the topic of the availability and use of genetic testing the Hungarian citizens had the most accepting opinion among the four countries, followed by the Czech citizens. In this domain the Polish and Slovak answers did not differ significantly from each other. CONCLUSIONS: Significant differences were observed even when considering various confounding effects. As the underlying reasons for these discrepancies are unknown, future studies should investigate this enigma among the four countries.

[Comparative analysis of the full and shortened versions of the Oldenburg Burnout Inventory]. / Az Oldenburg Kiégés Kérdôív és rövidített változatának összehasonlító elemzése.

Background - The two free-to-use versions of the Oldenburg Burnout Inventory (OLBI) have been increasingly utilised to assess the prevalence of burnout among human service workers. The OLBI has been developed to overcome some of the psychometric and conceptual limitations of the Maslach Burnout Inventory, the gold standard of burnout measures. There is a lack of data on the structural validity of the Mini Oldenburg Burnout Inventory and the Oldenburg Burnout Inventory in Hungary. Purpose - To assess the structural validity of the Hungarian versions of the Oldenburg Burnout Inventory and the Mini-Oldenburg Burnout Inventory. Methods - We enrolled 564 participants (196 healthcare workers, 104 nurses and 264 clinicians) in three cross-sectional surveys. In our analysis we assessed the construct validity of the instruments using confirmatory factor analysis and internal consistency using coefficient Cronbach's α. Results - We confirmed the two-dimensional structure (exhaustion and disengagement) of the Mini-Oldenburg Inventory and a shortened version of the Oldenburg Burnout Inventory Internal consistency coefficient confirmed the reliability of the instruments. The burnout appeared more than a 50 percent of the participants in every subsample. The prevalence of exhaustion was above 54.5% in each of the subsamples and the proportion of disengaged clinicians was particularly high (92%). Conclusions - Our findings provide support for the construct validity and reliability of the Hungarian versions of the Mini-Oldenburg Burnout Inventory and a shortened version of the Oldenburg Burnout Inventory in the assessment of burnout among clinicians and nurses in Hungary.

Deletion of the fungus specific protein phosphatase Z1 exaggerates the oxidative stress response in Candida albicans.

BACKGROUND: Candida albicans is an opportunistic pathogen which is responsible for widespread nosocomial infections. It encompasses a fungus specific serine/threonine protein phosphatase gene, CaPPZ1 that is involved in cation transport, cell wall integrity, oxidative stress response, morphological transition, and virulence according to the phenotypes of the cappz1 deletion mutant. RESULTS: We demonstrated that a short-term treatment with a sublethal concentration of tert-butyl hydroperoxide suppressed the growth of the fungal cells without affecting their viability, both in the cappz1 mutant and in the genetically matching QMY23 control strains. To reveal the gene expression changes behind the above observations we carried out a global transcriptome analysis. We used a pilot DNA microarray hybridization together with extensive RNA sequencing, and confirmed our results by quantitative RT-PCR. Novel functions of the CaPpz1 enzyme and oxidative stress mechanisms have been unraveled. The numbers of genes affected as well as the amplitudes of the transcript level changes indicated that the deletion of the phosphatase sensitized the response of C. albicans to oxidative stress conditions in important physiological functions like membrane transport, cell surface interactions, oxidation-reduction processes, translation and RNA metabolism. CONCLUSIONS: We conclude that in the wild type C. albicans CaPPZ1 has a protective role against oxidative damage. We suggest that the specific inhibition of this phosphatase combined with mild oxidative treatment could be a feasible approach to topical antifungal therapy.

Value-based genomic screening: exploring genomic screening for chronic diseases using triple value principles.

BACKGROUND: Genomic screening has unique challenges which makes it difficult to easily implement on a wide scale. If the costs, benefits and tradeoffs of investing in genomic screening are not evaluated properly, there is a risk of wasting finite healthcare resources and also causing avoidable harm. MAIN TEXT: If healthcare professionals - including policy makers, payers and providers - wish to incorporate genomic screening into healthcare while minimizing waste, maximizing benefits, and considering results that matter to patients, using the principles of triple value (allocative, technical, and personal value) could help them to evaluate tough decisions and tradeoffs. Allocative value focuses on the optimal distribution of limited healthcare resources to maximize the health benefits to the entire population while also accounting for all the costs of care delivery. Technical value ensures that for any given condition, the right intervention is chosen and delivered in the right way. Various methods (e.g. ACCE, HTA, and Wilson and Jungner screening criteria) exist that can help identify appropriate genomic applications. Personal value incorporates preference based informed decision making to ensure that patients are informed about the benefits and harms of the choices available to them and to ensure they make choices based on their values and preferences. CONCLUSIONS: Using triple value principles can help healthcare professionals make reasoned and tough judgements about benefits and tradeoffs when they are exploring the role genomic screening for chronic diseases could play in improving the health of their patients and populations.

Association between the application of ISO 9001:2008 alone or in combination with health-specific standards and quality-related activities in Hungarian hospitals.

OBJECTIVE: To investigate how International Organization for Standardization (ISO) 9001 and the Hungarian Health Care Standards (HHCS) certifications are associated with quality management, patient safety, patient rights and human resource management activities. DESIGN: A cross-sectional study was implemented using the 2009 Hungarian hospital survey's database. SETTING: Hungary. PARTICIPANTS: Fifty-three general hospitals were included in the statistical analysis. INTERVENTION: No intervention was carried out in the study. MAIN OUTCOME MEASURES: The outcomes included the percentage of compliance in the dimensions of quality management, patient safety, patient rights, human resource management and the overall score for each hospital, and they were grouped according to the hospitals' certifications. RESULTS: Sixteen hospitals did not have either ISO 9001 or HHCS certifications, 19 had ISO 9001 certification only and 18 had both. Hospitals with ISO 9001 alone or in combination with the HHCS significantly outperformed hospitals with no certifications in terms of quality management and human resource management activities but not in terms of patient safety or patient rights activities. Combined, the two models provided the highest median levels in all cases. Nevertheless, no significant differences were observed when the hospitals with both certifications were compared with hospitals with ISO 9001 only. CONCLUSIONS: Although the combination of ISO 9001 and the HHCS showed the best results, the benefits were not decisive. Furthermore, although the HHCS include standards addressing patient safety, no direct association was found with regard to compliance. Thus, further investigation is required to understand this enigma.

Effects of the glucocorticoid betamethasone on the interaction of Candida albicans with human epithelial cells.

The glucocorticoid betamethasone (BM) is frequently employed in clinical practice because of its anti-inflammatory and immunosuppressive properties. In this study, we investigated the effect of BM (1 and 2 mM) on the ability of Candida albicans to adhere to, invade and damage oral, intestinal or vaginal epithelial cells, as well as to elicit cytokine and chemokine release. BM at 2 mM concentration stimulated adherence of C. albicans to vaginal cells and facilitated the invasion of intestinal and vaginal epithelia without influencing the growth rate of invading C. albicans hyphae at any type of epithelia and BM concentrations tested. In addition, BM at 2 mM concentration also augmented C. albicans-initiated cell damage of oral and intestinal cells. Furthermore, BM exposure decreased IL-6 cytokine and IL-8 chemokine release from oral and vaginal epithelial cells and also IL-6 release from intestinal epithelium after infection with C. albicans. These observations suggest that high-dose applications of BM may predispose patients to various epithelial C. albicans infections.

The B″ regulatory subunit of protein phosphatase 2A mediates the dephosphorylation of rice retinoblastoma-related protein-1.

The phosphorylation of plant retinoblastoma-related (RBR) proteins by cyclin-dependent kinases (CDKs) is well documented, but the counteracting phosphatases have not been identified yet. We report here that rice retinoblastoma-related protein-1 (OsRBR1) interacted with the B″ subunit of rice protein phosphatase 2A (OsPP2A B″) and underwent reversible phosphorylation during the cell division cycle. The OsRBR1-OsPP2A B" association required B domain in OsRBR1 and the C-terminal region of OsPP2A B″. We found by immunoprecipitation that OsPP2A B″, OsPP2A catalytic subunit subtype II, PSTAIRE-type CDK and OsRBR1 were in the same protein complex, indicating a physical association between the phosphatase, the kinase and their common substrate. OsPP2A B″ contains three predicted CDK phosphorylation sites: Ser95, Ser102 and Ser119. The in vitro phosphorylation of Ser95 and Ser119 with PSTAIRE-kinases was verified by mass spectrometry. We generated a series of phosphorylation site mutants to mimic the dephosphorylated or phosphorylated states of OsPP2A B″, and confirmed that all of the three predicted sites can be phosphorylated. Yeast two-hybrid experiments suggested that the phosphorylation of OsPP2A B″ promoted the formation of the OsPP2A holoenzyme. A triple phosphorylation mimicking OsPP2A B″ mutant containing holoenzyme showed higher activity in phosphatase assays. Our data collectively show that the phosphatase activity of OsPP2A against OsRBR1 is regulated by the phosphorylation of its B″ regulatory subunit. However, the analysis of the effect of okadaic acid, a phosphatase inhibitor, in rice cell suspension cultures revealed that the dephosphorylation of OsRBR1 was completely inhibited only by high dose (300 nM) of the okadaic acid during the cell cycle progression. Therefore the role of the protein phosphatase 1 should be considered as an additional post translational regulatory component of RBR protein function in higher plants.

Betamethasone augments the antifungal effect of menadione--towards a novel anti-Candida albicans combination therapy.

The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology.

The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities.

Saccharomyces cerevisiae Hal3 and Vhs3 are moonlighting proteins, forming an atypical heterotrimeric decarboxylase (PPCDC) required for CoA biosynthesis, and regulating cation homeostasis by inhibition of the Ppz1 phosphatase. The Schizosaccharomyces pombe ORF SPAC15E1.04 (renamed as Sp hal3) encodes a protein whose amino-terminal half is similar to Sc Hal3 whereas its carboxyl-terminal half is related to thymidylate synthase (TS). We show that Sp Hal3 and/or its N-terminal domain retain the ability to bind to and modestly inhibit in vitro S. cerevisiae Ppz1 as well as its S. pombe homolog Pzh1, and also exhibit PPCDC activity in vitro and provide PPCDC function in vivo, indicating that Sp Hal3 is a monogenic PPCDC in fission yeast. Whereas the Sp Hal3 N-terminal domain partially mimics Sc Hal3 functions, the entire protein and its carboxyl-terminal domain rescue the S. cerevisiae cdc21 mutant, thus proving TS function. Additionally, we show that the 70 kDa Sp Hal3 protein is not proteolytically processed under diverse forms of stress and that, as predicted, Sp hal3 is an essential gene. Therefore, Sp hal3 represents a fusion event that joined three different functional activities in the same gene. The possible advantage derived from this surprising combination of essential proteins is discussed.

Time-lapse video microscopy and image analysis of adherence and growth patterns of Candida albicans strains.

Digital image analysis of high time resolution video microscopy was used to investigate hyphal growth dynamics in different Candida albicans strains. The effects of the quorum sensing molecules tyrosol and farnesol, the deletion of the fungus specific protein phosphatase Z1 CaPPZ1), and the hypha-specific cyclin (HGC1) genes were analyzed by this method. Our system monitored cell growth in a CO2 incubator under near-physiological conditions and measured three major parameters under the following stringent conditions: (a) the time of yeast cell adherence, (b) the time of hyphal outgrowth, and (c) the rate of hyphal growth. This method showed that hyphal extension of wild-type SC5314 cells was accelerated by tyrosol and inhibited by farnesol. Hyphal growth rate was moderately lower in cappz1 and strongly reduced in hgc1 mutants. In addition, tyrosol treatment caused a firm adherence, while farnesol treatment and hgc1 mutation prevented the adherence of yeast cells to the surface of the culture flask. Transition from yeast-to-hyphal state was faster after tyrosol treatment, while it was reduced in farnesol-treated cells as well as in the cappz1 and hgc1 mutants. Our data confirm the notion that the attachment of yeast cells, the yeast-to-hyphal transition, and hyphal growth rate are closely related processes. Time-lapse video microscopy combined with image analysis offers a convenient and reliable method of testing chemicals, including potential drug candidates, and genetic manipulations on the dynamic morphological changes in C. albicans strains.

Factors Associated With Cervical Cancer Screening Attendance in Hungary Based on the European Health Interview Survey.

Objectives: This study assessed the change in cervical cancer screening attendance across 10 years and identified the associated factors. Methods: Data from the European Health Interview Surveys in Hungary (2009, 2014, 2019) were analyzed with multivariate and multiple logistic regressions. Results: The analysis involved 4,850 participants, revealing a significant (p < 0.001) increase in screening attendance from 69% to 77% over 10 years. Factors significantly associated with higher attendance rates included a higher education level (tertiary level AOR = 2.51 [2.03-3.09]), being in a relationship (AOR = 1.59 [1.39-1.83]), the belief that one can do much for one's health (OR = 1.26 [1.05-1.52]), and the absence of chronic health problems (AOR = 1.56 [1.33-1.84]). Lower screening odds were significantly correlated with worse self-perceived health status (AOR = 0.65 [0.52-0.81]) and less frequent doctor (AOR = 0.64 [0.54-0.76]) and specialist visits (AOR = 0.46 [0.39-0.53]). Conclusion: Enhancing cervical cancer screening rates requires tailored public health strategies, particularly targeting individuals with lower education and poor health perceptions. Public health initiatives and enhanced collaboration among healthcare professionals are required to further increase participation rates, particularly among the identified groups.

Changes in Antibiotic Redemption Related to Hungarian Dental Care During COVID-19.

INTRODUCTION AND AIMS: Antibiotic resistance is a global health problem that can affect individuals, health systems, and the economy. Our aim was to investigate how the redemption of antibiotics and the associated dental care changed during COVID-19 in Hungary. METHODS: The ICD codes for the infections for which antibiotics should be prescribed in dental care were identified based on the professional recommendation. The database was provided by the National Health Insurance Fund Manager of Hungary. Pearson's chi-squared test with Bonferroni correction was used to compare both the redemption of antibiotics and the associated dental care based on the recommendations in the year 2020 of the COVID-19 and the 2 preceding years. RESULTS: There were fewer antibiotic redemptions and associated dental care in 2020 than in 2018 and 2019. The ratio of professionally relevant and nonrelevant antibiotics redeemed did not change significantly between 2018 and 2019, but the proportion of antibiotics redeemed following recommendations increased significantly during the COVID-19 year of 2020 compared to the previous 2 years. The proportion of all dental care involving antibiotic redemptions increased significantly from 2018 to 2019, and then showed a further increase in 2020. The sex and age of the patient did not affect these findings, while the type of dental care did alter the trends in some cases. CONCLUSIONS: Antibiotics in dentistry are required only for very low proportion of cases, due to the nature of dental care where most infections such as caries and periodontal disease could be managed without resorting to antibiotics. Antibiotic redemptions during COVID-19 pandemic period increased compared to the pre-pandemic period in Hungary. Therefore, Hungarian policy makers need to develop control systems to promote the correct use of antibiotics in dental care. CLINICAL RELEVANCE: It is important to reduce unjustified use of antibiotics so as to curb the emergence of antibiotic resistance organisms.

Influenza Vaccination Coverage among People with Self-Reported Cardiovascular Diseases-Findings from the Hungarian Implementation of the European Health Interview Survey.

Worldwide, cardiovascular diseases are the leading cause of mortality. This has significant implications for public health. Influenza, a common infectious disease, poses an increased risk for individuals with chronic conditions, such as cardiovascular diseases. However, little is known about influenza vaccination coverage in this group. This study utilized data from the Hungarian implementation of the European Health Interview Survey to assess influenza vaccination coverage and its determinants among cardiovascular respondents from 2009 to 2019. The findings reveal a downward trend in the vaccination rates over the years (from 24% to 21%), despite the availability of free vaccination in Hungary for this high-risk population. The main factors influencing low influenza vaccine uptake were identified, as follows: young age, a lower level of education, good self-perceived health status, smoking, a lower frequency of medical visits, and not suffering from respiratory diseases. Addressing these disparities necessitates targeted vaccination strategies supported by enhanced education, better access to healthcare services, and the promotion of preventive healthcare measures. Improving vaccination coverage among patients with cardiovascular diseases is imperative for reducing influenza-related morbidity and mortality. This highlights the importance of comprehensive public health interventions and healthcare provider engagement in promoting vaccination among groups at increased risk.

Comparison of Executive Function Skills between Patients with Cerebral Palsy and Typically Developing Populations: A Systematic Review and Meta-Analysis.

Background: Children with CP show deficits in executive function compared to their typically developing peers, based on the majority of the available evidence. However, the magnitude of these deficits, as well as the proportions of the shortfalls in the three main components, have not yet been examined. This is the first meta-analysis to synthesize evidence on the magnitude of differences between patients with cerebral palsy (CP) and typically developing populations in different components of executive function skills (working memory, inhibitory control and cognitive flexibility), and thus makes recommendations on which areas of executive functioning are in greatest need of intervention. Methods: We conducted a systematic literature search of four databases for studies that measured executive functions in these two groups until 31 August 2023. We calculated the standardized mean difference (Hedges' g), an average effect size overall, and for the three components of executive function skills separately, we used several moderator analyses, including methodological differences between the primary studies. Results: Fifteen articles were included in the meta-analysis. The average mean difference in executive functioning overall was large (g+ = -0.82). Furthermore, large significant differences were found in working memory (g+ = -0.92) and inhibitory control (g+ = -0.82) and a moderate difference was identified in cognitive flexibility (g+ = -0.57). In addition, results of moderator analyses reveal the importance of a rigorous matching of control group participants and CP patients. Conclusions: The results demonstrate a severe impairment in all executive functions among CP patients compared to typically developing peers, which do not decrease over time.

CalpB modulates border cell migration in Drosophila egg chambers.

BACKGROUND: Calpains are calcium regulated intracellular cysteine proteases implicated in a variety of physiological functions and pathological conditions. The Drosophila melanogaster genome contains only two genes, CalpA and CalpB coding for canonical, active calpain enzymes. The movement of the border cells in Drosophila egg chambers is a well characterized model of the eukaryotic cell migration. Using this genetically pliable model we can investigate the physiological role of calpains in cell motility. RESULTS: We demonstrate at the whole organism level that CalpB is implicated in cell migration, while the structurally related CalpA paralog can not fulfill the same function. The downregulation of the CalpB gene by mutations or RNA interference results in a delayed migration of the border cells in Drosophila egg chambers. This phenotype is significantly enhanced when the focal adhesion complex genes encoding for α-PS2 integrin ( if), ß-PS integrin (mys) and talin (rhea) are silenced. The reduction of CalpB activity diminishes the release of integrins from the rear end of the border cells. The delayed migration and the reduced integrin release phenotypes can be suppressed by expressing wild-type talin-head in the border cells but not talin-head(R367A), a mutant form which is not able to bind ß-PS integrin. CalpB can cleave talin in vitro, and the two proteins coimmunoprecipitate from Drosophila extracts. CONCLUSIONS: The physiological function of CalpB in border cell motility has been demonstrated in vivo. The genetic interaction between the CalpB and the if, mys, as well as rhea genes, the involvement of active talin head-domains in the process, and the fact that CalpB and talin interact with each other collectively suggest that the limited proteolytic cleavage of talin is one of the possible mechanisms through which CalpB regulates cell migration.

Protein phosphatase CaPpz1 is involved in cation homeostasis, cell wall integrity and virulence of Candida albicans.

The opportunistic pathogen Candida albicans has a single protein phosphatase Z (PPZ) candidate gene termed CaPPZ1, which shows significant allele variability. We demonstrate here that bacterially expressed CaPpz1 protein exhibits phosphatase activity which can be inhibited by recombinant Hal3, a known inhibitor of Saccharomyces cerevisiae Ppz1. Site-directed mutagenesis experiments based on natural polymorphisms allowed the identification of three amino acid residues that affect enzyme activity or stability. The expression of CaPPZ1 in ppz1 S. cerevisiae and pzh1 Schizosaccharomyces pombe cells partially rescued the salt and caffeine phenotypes of the deletion mutants. CaPpz1 also complemented the slt2 S. cerevisiae mutant, which is crippled in the mitogen-activated protein (MAP) kinase that mediates the cell wall integrity signalling pathway. Collectively, our results suggest that the orthologous PPZ enzymes have similar but not identical functions in different fungi. The deletion of the CaPPZ1 gene in C. albicans resulted in a mutant that was sensitive to salts such as LiCl and KCl, to caffeine, and to agents that affect cell wall biogenesis such as Calcofluor White and Congo red, but was tolerant to spermine and hygromycin B. Reintegration of the CaPPZ1 gene into the deletion mutant alleviated all of the mutant phenotypes tested. Thus CaPpz1 is involved in cation homeostasis, cell wall integrity and the regulation of the membrane potential of C. albicans. In addition, the germ tube growth rate, and virulence in the BALB/c mouse model, were reduced in the null mutant, suggesting a novel function for CaPpz1 in the yeast to hypha transition that may have medical relevance.

Protein phosphatase Z modulates oxidative stress response in fungi.

The genome of the filamentous fungus Aspergillus nidulans harbors the gene ppzA that codes for the catalytic subunit of protein phosphatase Z (PPZ), and the closely related opportunistic pathogen Aspergillus fumigatus encompasses a highly similar PPZ gene (phzA). When PpzA and PhzA were expressed in Saccharomyces cerevisiae or Schizosaccharomyces pombe they partially complemented the deleted phosphatases in the ppz1 or the pzh1 mutants, and they also mimicked the effect of Ppz1 overexpression in slt2 MAP kinase deficient S. cerevisiae cells. Although ppzA acted as the functional equivalent of the known PPZ enzymes its disruption in A. nidulans did not result in the expected phenotypes since it failed to affect salt tolerance or cell wall integrity. However, the inactivation of ppzA resulted in increased sensitivity to oxidizing agents like tert-butylhydroperoxide, menadione, and diamide. To demonstrate the general validity of our observations we showed that the deletion of the orthologous PPZ genes in other model organisms, such as S. cerevisiae (PPZ1) or Candida albicans (CaPPZ1) also caused oxidative stress sensitivity. Thus, our work reveals a novel function of the PPZ enzyme in A. nidulans that is conserved in very distantly related fungi.