Showing papers by "University of Rijeka published in 2007"
Bradley University1, University of Tartu2, National Institutes of Health3, University of California4, Pontifical Catholic University of Chile5, University of Louisville6, University of Latvia7, Pennsylvania State University8, Slovak Academy of Sciences9, University of San Carlos10, University of Malta11, Ghent University12, Clemson University13, Laval University14, University of Buenos Aires15, Osaka University16, Illinois State University17, National Autonomous University of Mexico18, University of Brasília19, University of Western Australia20, University of Lima21, Boğaziçi University22, University of Kassel23, York University24, University of Queensland25, Åbo Akademi University26, Al Akhawayn University27, University of Hawaii at Manoa28, University of Catania29, University of Otago30, University of Dhaka31, Chemnitz University of Technology32, Knox College33, Comenius University in Bratislava34, University of Rijeka35, University of Malaya36, Vilnius University37, American University of Beirut38, Kwangju Health College39, University of Salzburg40, Utrecht University41, National Computerization Agency42, City University of Hong Kong43, University of Idaho44, University of Zimbabwe45, University of Lisbon46, University of Central Lancashire47, Loyola Marymount University48, University of KwaZulu-Natal49, University of Granada50, University of Botswana51, Babeș-Bolyai University52, University of Cyprus53, University of Belgrade54, KPMG55, University of Montpellier56, University of Zurich57, University of Alabama58, Baylor University59, Queen's University Belfast60, University of Ljubljana61, University of Haifa62, University of La Serena63, Florida Atlantic University64, University of California, Davis65, University of Dar es Salaam66, Ramapo College67, Cyprus College68, Middle East Technical University69, Nicolaus Copernicus University in Toruń70, University of the South Pacific71, Vrije Universiteit Brussel72, University at Albany, SUNY73, University of the Aegean74, University of Lethbridge75, University of Vienna76, University of Hong Kong77, Yuan Ze University78, Charles University in Prague79, Chonnam National University80, Indian Institutes of Technology81
TL;DR: The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness as discussed by the authors.
Abstract: The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness. As part of the International Sexuality Description Project, the BFI was translated from English into 28 languages and administered to 17,837 individuals from 56 nations. The resulting cross-cultural data set was used to address three main questions: Does the factor structure of the English BFI fully replicate across cultures? How valid are the BFI trait profiles of individual nations? And how are personality traits distributed throughout the world? The five-dimensional structure was robust across major regions of the world. Trait levels were related in predictable ways to self-esteem, sociosexuality, and national personality profiles. People from the geographic regions of South America and East Asia were significantly different in openness from those inhabiting other world regions. The discussion focuses on limitations of t...
876 citations
TL;DR: Progesterone is critical for the establishment and the maintenance of pregnancy, both by its endocrine and immunological effects as mentioned in this paper, and it plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors.
Abstract: Progesterone is critical for the establishment and the maintenance of pregnancy, both by its endocrine and immunological effects. The genomic actions of progesterone are mediated by the intracellular progesterone receptors; A and B. A protein called P-induced blocking factor (PIBF), by inducing a T(H2) dominant cytokine production, mediates the immunological effects of progesterone. Progesterone plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors. At high concentrations progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. Though a key role for progesterone in creating local immunosuppression has been conserved during the evolution of an epitheliochorial placenta, there has been some divergence in the pattern of endocrine-immunological cross talk in Bovidae. In sheep, uterine serpin, a progesterone-induced endometrial protein, mediates the immunosuppressive effects of progesterone. Epidemiological studies suggest the role of stress in premature pregnancy termination and exposure to stress induces abortion in mice via a significant reduction in progesterone levels, accompanied by reduced serum levels of PIBF. These effects are corrected by progesterone supplementation. These findings indicate the significance of a progesterone-dependent immuno-modulation in maternal tolerance of the fetus, which is discussed in this review.
239 citations
Babraham Institute1, Lund University2, Los Alamos National Laboratory3, University College Dublin4, University of Provence5, University of Bordeaux6, Braunschweig University of Technology7, European Bioinformatics Institute8, University of Kassel9, German Cancer Research Center10, University of Tübingen11, Max Planck Society12, Uppsala University13, Leiden University Medical Center14, Wellcome Trust Sanger Institute15, VU University Amsterdam16, Royal Institute of Technology17, University of Zurich18, University of Rijeka19, University of Konstanz20, Technische Universität München21
TL;DR: ProteomeBinders is a new European consortium aiming to establish a comprehensive resource of well-characterized affinity reagents, including but not limited to antibodies, for analysis of the human proteome.
Abstract: ProteomeBinders is a new European consortium aiming to establish a comprehensive resource of well-characterized affinity reagents, including but not limited to antibodies, for analysis of the human proteome. Given the huge diversity of the proteome, the scale of the project is potentially immense but nevertheless feasible in the context of a pan-European or even worldwide coordination.
238 citations
TL;DR: The promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies.
Abstract: Fetal loss in animals and humans is frequently associated with inflammatory conditions. D6 is a promiscuous chemokine receptor with decoy function, expressed in lymphatic endothelium, that recognizes and targets to degradation most inflammatory CC chemokines. Here, we report that D6 is expressed in placenta on invading extravillous trophoblasts and on the apical side of syncytiotrophoblast cells, at the very interface between maternal blood and fetus. Exposure of D6−/− pregnant mice to LPS or antiphospholipid autoantibodies results in higher levels of inflammatory CC chemokines and increased leukocyte infiltrate in placenta, causing an increased rate of fetal loss, which is prevented by blocking inflammatory chemokines. Thus, the promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies.
181 citations
TL;DR: Uterine dendritic cells within the decidua serve as antigen-presenting cells with the unique ability to induce primary immune responses and may also act to induce immunologic tolerance and regulation of T cell-mediated immunity.
Abstract: Pregnancy is a unique event in which a fetus, despite being genetically and immunologically different from the mother (a hemi-allograft), develops in the uterus. Successful pregnancy implies avoidance of rejection by the maternal immune system. Fetal and maternal immune cells come into direct contact at the decidua, which is a highly specialized mucous membrane that plays a key role in fetal tolerance. Uterine dendritic cells (DC) within the decidua have been implicated in pregnancy maintenance. DC serve as antigen-presenting cells with the unique ability to induce primary immune responses. Just as lymphocytes comprise different subsets, DC subsets have been identified that differentially control lymphocyte function. DC may also act to induce immunologic tolerance and regulation of T cell-mediated immunity. Current understanding of DC immunobiology within the context of mammalian fetal-maternal tolerance is reviewed and discussed herein.
173 citations
TL;DR: A literal replication of Fenton and Ohlsson's study on fault distributions confirms that the uneven distribution of defects motivates uneven Distribution of quality assurance efforts, although predictors for such distribution of efforts are not sufficiently precise.
Abstract: To contribute to the body of empirical research on fault distributions during development of complex software systems, a replication of a study of Fenton and Ohlsson is conducted. The hypotheses from the original study are investigated using data taken from an environment that differs in terms of system size, project duration, and programming language. We have investigated four sets of hypotheses on data from three successive telecommunications projects: 1) the Pareto principle, that is, a small number of modules contain a majority of the faults (in the replication, the Pareto principle is confirmed), 2) fault persistence between test phases (a high fault incidence in function testing is shown to imply the same in system testing, as well as prerelease versus postrelease fault incidence), 3) the relation between number of faults and lines of code (the size relation from the original study could be neither confirmed nor disproved in the replication), and 4) fault density similarities across test phases and projects (in the replication study, fault densities are confirmed to be similar across projects). Through this replication study, we have contributed to what is known on fault distributions, which seem to be stable across environments.
149 citations
TL;DR: The utility of the approach is tested by comparing the autocorrelation and cross-correlation properties of the time series generated by the model with data on daily returns for two major financial indices, the Dow Jones and the S&P500, and on daily return of two well-known company stocks, IBM and Microsoft, over five years.
Abstract: We develop a stochastic process with two coupled variables where the absolute values of each variable exhibit long-range power-law autocorrelations and are also long-range cross-correlated. We investigate how the scaling exponents characterizing power-law autocorrelation and long-range cross-correlation behavior in the absolute values of the generated variables depend on the two parameters in our model. In particular, if the autocorrelation is stronger, the cross-correlation is also stronger. We test the utility of our approach by comparing the autocorrelation and cross-correlation properties of the time series generated by our model with data on daily returns over ten years for two major financial indices, the Dow Jones and the S&P500, and on daily returns of two well-known company stocks, IBM and Microsoft, over five years.
125 citations
TL;DR: This review focuses on the characterization of decidual macrophages and DCs, as well as their involvement in cell–cell interactions within the decidUAL leukocyte network, which are likely to influence uterine and placental homeostasis as wellAs the local maternal immune responses to the fetus during pregnancy.
Abstract: During pregnancy, a delicate balance of innate and adaptive immune responses at the maternal-fetal interface promotes survival of the semi-allogeneic embryo and, at the same time, allows effective immunity to protect the mother from environmental pathogens. As in other tissues, antigen handling and processing in the decidualized endometrium constitutes a primary event in the onset of immune responses and is therefore likely to determine their stimulatory or tolerogenic nature. Maternal antigen-presenting cells [macrophages and dendritic cells (DCs)] are scattered throughout the decidualized endometrium during all stages of pregnancy and appear to be important players in this feto-maternal immune adjustment. This review focuses on the characterization of decidual macrophages and DCs, as well as their involvement in cell-cell interactions within the decidual leukocyte network, which are likely to influence uterine and placental homeostasis as well as the local maternal immune responses to the fetus during pregnancy.
117 citations
TL;DR: In this paper, the authors compared problem-specific coping strategies and coping styles of European adolescents from seven nations, including Croatia, Czech Republic, Germany, Italy, Norway, Portugal, and Switzerland.
Abstract: The present study compares problem-specific coping strategies and coping styles of European adolescents from seven nations. The sample consisted of 3031 adolescent participants, aged 11 to 20, from Croatia, the Czech Republic, Germany, Italy, Norway, Portugal, and Switzerland. The adolescents completed the Coping Across Situations Questionnaire (CASQ) by indicating which coping strategies (from 20 alternatives) they usually employed in dealing with age-specific problems (covering 8 different domains). The strategies can be collapsed to three coping styles: active coping, internal coping, and withdrawal. Results show that adolescents from all seven nations predominantly employed functional forms of coping, i.e., active coping and internal coping. In addition, the pattern of frequently and rarely applied coping strategies was similar across cultures. Differences in coping style were revealed for some, but not all problem domains, suggesting that cross-cultural similarity in coping exists for specific stressors. Problem-specific analyses helped to clarify where cultural influence is most distinct. Whereas cultural diversity was highest for coping with job-related problems, coping with self- and future-related problems was highly similar among adolescents from all the nations. Despite the considerable traditional, educational, and economic differences among the cultures investigated, the similarities in coping behaviour were impressive. Explanations for cultural universals and differences in adolescent coping are discussed.
111 citations
TL;DR: Evidence is provided that a cell-based strategy to support the humoral immune response can be effective to combat infectious pathogens in severely immunodeficient hosts.
108 citations
TL;DR: It is shown that the FPI protein IglD is essential for intracellular replication in primary human monocyte‐derived macrophages (hMDMs), the first demonstration of a F.’tularensis novel protein essential for proliferation in the macrophage cytosol.
Abstract: Summary Francisella tularensis is an intracellular bacterial pathogen, and is a category A bioterrorism agent. Within quiescent human macrophages, the F. tularensis pathogenicity island (FPI) is essential for bacterial growth within quiescent macrophages. The F. tularensis-containing phagosome matures to a late endosome-like stage that does not fuse to lysosomes for 1-8 h, followed by gradual bacterial escape into the macrophage cytosol. Here we show that the FPI protein IglD is essential for intracellular replication in primary human monocyte-derived macrophages (hMDMs). While the parental strain replicates robustly in pulmonary, hepatic and splenic tissues of BALB/c mice associated with severe immunopathologies, the isogenic iglD mutant is severely defective. Within hMDMs, the iglD mutant-containing phagosomes mature to either a late endosome-like phagosome, similar to the parental strain, or to a phagolysosome, similar to phagosomes harbouring the iglC mutant control. Despite heterogeneity and alterations in pha- gosome biogenesis, the iglD mutant bacteria escape into the cytosol faster than the parental strain within hMDMs and pulmonary cells of BALB/c mice. Co-infections of hMDMs with the wild-type strain and the iglD mutant, or super-infection of iglD mutant- infected hMDMs with the wild-type strain show that the mutant strain replicates robustly within the cytosol of hMDMs coinhabited by the wild strain. However, when the wild-type strain-infected hMDMs are super-infected by the iglD mutant, the mutant fails to replicate in the cytosol of communal macrophages. This is the first demonstration of a F. tularensis novel protein essential for proliferation in the macrophage cytosol. Our data indicate that F. tularensis trans- duces signals to the macrophage cytosol to remodel it into a proliferative niche, and IglD is essential for transduction of these signals.
TL;DR: Objective analysis of the TNF-α levels enables establishment of a relationship between different concentrations of T NF-α and different radiological changes, from smaller to bigger lesions.
Abstract: Aim. The aim of this study was to determine tumor necrosis factor-alpha (TNF-α) levels in periapical exudates and to evaluate their relationship with radiological findings. Methodology. Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-α levels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area. Results. Nonparametric Kruskal-Wallis test revealed significant differences between TNF-α concentrations in control group (40, 57±28, 15 pg/mL) and group with larger radiolucent areas (2365, 79±582, 95 pg/mL), as well as between control and canals with small radiolucent areas (507, 66±278, 97) (P<.05). Conclusions. The levels of TNF-α increase significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-α levels enables establishment of a relationship between different concentrations of TNF-α and different radiological changes.
TL;DR: Modulation of C. jejuni virulence in response to environmental stress factors may have further implications in the pathogenesis of campylobacteriosis.
TL;DR: The most frequent errors in calculating correlation are related to conditions for calculation, interpretation of the coefficient and correlation significance, high correlation coefficients, assumption of causal relationship, the strength of correlation (coefficient of determination), and comparison of two correlation coefficients as discussed by the authors.
Abstract: Correlation is a statistical procedure applied to calculate association between two variables. The value of correlation is numerically shown by a coefficient of correlation, most often by Pearson's or Spearman's coefficient, while the significance of the coefficient is expressed by P value. The coefficient of correlation shows the extent to which changes in the value of one variable are correlated to changes in the value of the other. A sign preceding the coefficient of correlation (+ or -) indicates the direction of correlation. The most frequent errors in calculating correlation are related to conditions for calculation, interpretation of the coefficient and correlation significance, high correlation coefficients, assumption of causal relationship, the strength of correlation (coefficient of determination), and comparison of two correlation coefficients.
TL;DR: In this article, the authors report quantitative relations between corruption level and economic factors, such as country wealth and foreign investment per capita, characterized by a power law spanning multiple scales of wealth and investment per person.
Abstract: We report quantitative relations between corruption level and economic factors, such as country wealth and foreign investment per capita, which are characterized by a power law spanning multiple scales of wealth and investment per capita. These relations hold for diverse countries, and also remain stable over different time periods. We also observe a negative correlation between level of corruption and long-term economic growth. We find similar results for two independent indices of corruption, suggesting that the relation between corruption and wealth does not depend on the specific measure of corruption. The functional relations we report have implications when assessing the relative level of corruption for two countries with comparable wealth, and for quantifying the impact of corruption on economic growth and foreign investment.
TL;DR: In this paper, a new model-independent method of comparison of NIR visibility data of YSOs is presented, based on scaling the measured baseline with the YSO's distance and luminosity, which removes the dependence of visibility on these two variables.
Abstract: We present a new model-independent method of comparison of NIR visibility data of YSOs. The method is based on scaling the measured baseline with the YSO's distance and luminosity, which removes the dependence of visibility on these two variables. We use this method to compare all available NIR visibility data and demonstrate that it distinguishes YSOs of luminosity L 103 L? (low L) from YSOs of L 103 L? (high L). This confirms earlier suggestions, based on fits of image models to the visibility data, for the difference between the NIR sizes of these two luminosity groups. When plotted against the scaled baseline, the visibility creates the following data clusters: low-L Herbig Ae/Be stars, T Tauri stars, and high-L Herbig Be stars. We model the shape and size of clusters with different image models and find that low-L Herbig stars are best explained by the uniform brightness ring and the halo model, T Tauri stars with the halo model, and high-L Herbig stars with the accretion disk model. However, the plausibility of each model is not well established. Therefore, we try to build a descriptive model of the circumstellar environment consistent with various observed properties of YSOs. We argue that low-L YSOs have optically thick disks with the optically thin inner dust sublimation cavity and an optically thin dusty outflow above the inner disk regions. High-L YSOs have optically thick accretion disks with high accretion rates enabling gas to dominate the NIR emission over dust. Although observations would favor such a description of YSOs, the required dust distribution is not supported by our current understanding of dust dynamics.
TL;DR: The results indicate that symptomatic lesions represent an immunologically active stage of disease, and asymptomatic lesions are the point from which the process advances toward healing.
Abstract: Aim. The aim of this study was to evaluate the presence of the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in human periapical lesions. Subjects and methods. Samples were obtained from three groups of teeth: symptomatic teeth, asymptomatic lesions, and uninflamed periradicular tissues as a control. Results. TNF-alpha levels were significantly increased in symptomatic lesions compared to control. Group with asymptomatic lesions had significantly higher concentrations compared to control. There were no significant differences in TNF-alpha levels between symptomatic and asymptomatic lesions. In group with symptomatic lesions, IL-6 levels were significantly higher than in group with asymptomatic lesions. The IL-6 levels in symptomatic group also showed significantly higher concentration in comparison with control group. In asymptomatic group, the IL-6 level had significantly higher concentrations compared to control. Conclusion. These results indicate that symptomatic lesions represent an immunologically active stage of disease, and asymptomatic lesions are the point from which the process advances toward healing.
TL;DR: According to the spatial registration hypothesis, the representation of stimulus location is automatically encoded during perception and it can interact with a more abstract linguistic representation as mentioned in this paper, and reaction times showed significant interaction between the spatial position and the word type.
Abstract: According to the spatial registration hypothesis, the representation of stimulus location is automatically encoded during perception and it can interact with a more abstract linguistic representation. We tested this hypothesis in two experiments, using the semantic judgements of words. In the first experiment, words for animals that either fly or do not fly were presented either in the upper or lower part of a display relative to the fixation point. Reaction times showed significant interaction between the spatial position and the word type. The words for flying animals were judged faster when they were presented in the upper part while the words for non-flying animals were processed faster in the lower part of the display. In the second experiment we extended the stimulus set to words denoting non-living things which are associated with either upper or lower spatial position. Again, reaction times showed significant interaction between the actual spatial position where the words were presented, and their...
TL;DR: In this paper, the phase transition temperatures of model systems were determined using differential thermal analysis with continuous scanning, and they were analyzed for emulsion activity index (EAI) and emulsion stability index (ESI) by the turbidometric technique.
Journal Article•
TL;DR: Results revealed significantly poor level of oral hygiene and quite high level of caries prevalence in both disabled and healthy children, accentuating the need to reorganize preventive care measurements and improve dental care, particularly in disabled children in Croatia.
Abstract: The aim of the study was to evaluate oral health conditions and dental caries status in disabled and healthy children. Two groups of randomly selected children 3-17 years old were examined. The first group comprised 80 children with disabilities (cerebral palsy, mental retardation, Down syndrome, autism and hearing-speaking disorders) and the second (control) group included 80 healthy children. Examined children were selected from several institutions which take care of disabled persons, kindergardens and four elementary schools. Clinical examination was performed by using a mirror and a probe and revealed the presence of dental caries, missing (extracted) and filled teeth. All clinically detected cavitations were registered as dental caries. The degree of oral hygiene was evaluated according to the OHI-S index values, which was determined by marking the plaque with 1% eozine solution. The values of OHI-S index ranged from 3.8-4.53 in disabled children and 2.73-2.84 in healthy children. In disabled children, the average dft values were 3.42 in deciduous teeth and 5.24 in mixed dentition. In healthy children, the average dft values were 1.43 in deciduous teeth and 5.1 in mixed dentition. The average DMFT index in disabled children was 1.41 for mixed and 6.39 for permanent dentitions. In healthy children, the average DMFT values were 1.23 in mixed and 4.76 in permanent dentitions. In general, the results revealed significantly poor level of oral hygiene and quite high level of caries prevalence in both disabled and healthy children, accentuating the need to reorganize preventive care measurements and improve dental care, particularly in disabled children in Croatia.
TL;DR: A significant effect of environmental factors on body height and craniofacial variability was found in Croatian young adult population, and was more pronounced in females, revealing sex-specific craniometric differentiation.
Abstract: Background: Craniometric variation in humans reflects different genetic and environmental influences. Long-term climatic adaptation is less likely to show an impact on size and shape variation in a...
Journal Article•
TL;DR: If the balance testing results prove to be effective in predicting the occurrence of ligament injuries during future sports activities, it is suggested that prophylactic training programs be introduced during athlete training, since the prevention of an initial injury will be more effective than prevention of injury recurrence.
Abstract: Female athletes participating in high-risk sports suffer anterior cruciate ligament (ACL) knee injury at a 4- to 6-fold greater rate than do male athletes. ACL injuries result either from contact mechanisms or from certain unexplained non-contact mechanisms occurring during daily professional sports activities. The occurrence of non-contact injuries points to the existence of certain factors intrinsic to the knee that can lead to ACL rupture. When knee joint movement overcomes the static and the dynamic constraint systems, non-contact ACL injury may occur. Certain recent results suggest that balance and neuromuscular control play a central role in knee joint stability, protection and prevention of ACL injuries. The purpose of this study is to evaluate balance neuromuscular skills in healthy Croatian female athletes by measuring their balance index score, as well as to estimate a possible correlation between their balance index score and balance effectiveness. This study is conducted in an effort to reduce the risk of future injuries and thus prevent female athletes from withdrawing from sports prematurely. We analysed fifty-two female athletes in the high-risk sports of handball and volleyball, measuring for their static and dynamic balance index scores, using the Sport KAT 2000 testing system. This method may be used to monitor balance and coordination systems and may help to develop simpler measurements of neuromuscular control, which can be used to estimate risk predictors in athletes who withdraw from sports due to lower sports results or ruptured anterior cruciate ligament and to direct female athletes to more effective, targeted preventive interventions. The tested Croatian female athletes with lower sports results and ACL knee injury incurred after the testing were found to have a higher balance index score compared to healthy athletes. We therefore suggest that a higher balance index score can be used as an effective risk predictor for lower sports results and lesser sports motivation, anterior cruciate ligament injury and the ultimate decision to withdraw from active participation in sports. If the balance testing results prove to be effective in predicting the occurrence of ligament injuries during future sports activities, we suggest that prophylactic training programs be introduced during athlete training, since the prevention of an initial injury will be more effective than prevention of injury recurrence.
TL;DR: A point-prevalence survey of five European university hospitals was performed to benchmark antimicrobial drug use in order to identify potential problem areas in prescribing practice and to aid in establishing appropriate and attainable goals.
TL;DR: It is proposed that a targeted and rational approach can improve future herpesvirus vaccines and vaccine vectors, including CMV vaccines, by deleting 32 genes from the mouse cytomegalovirus genome.
Abstract: Human cytomegalovirus (CMV), a ubiquitous human pathogen, is a leading cause of congenital infections and represents a serious health risk for the immunosuppressed patient. A vaccine against CMV is currently not available. CMV is characterized by its large genome and by multiple genes modulating the immunity of the host, which cluster predominantly at genome termini. Here, we tested whether the deletion of gene blocks rich in immunomodulatory genes could be used as a novel concept in the generation of immunogenic but avirulent, herpesvirus vaccines. To generate an experimental CMV vaccine, we selectively deleted 32 genes from the mouse cytomegalovirus (MCMV) genome. The resulting mutant grew to titers similar to that of wild-type MCMV in vitro. In vivo, the mutant was 10,000-fold attenuated and well tolerated, even by highly susceptible mice deficient for B, T, and NK cells or for the interferon type I receptor. Equally relevant for safety concerns, immune suppression did not lead to the mutant's reactivation from latency. Immunization with the replication-competent mutant, but not with inactivated virus, resulted in protective immunity, which increased over time. Vaccination induced MCMV-specific antibodies and a strong T-cell response. We propose that a targeted and rational approach can improve future herpesvirus vaccines and vaccine vectors.
TL;DR: The authors explored the comprehension monitoring, use of reading strategies and reading comprehension of bilingual students at different levels of the Italian language proficiency, and found that the bilingual students in the higher elementary school grades, who are more proficient in Italian, have better metacognitive reading skills than the less proficient students.
Abstract: The aim of this study was to explore the comprehension monitoring, use of reading strategies and reading comprehension of bilingual students at different levels of the Italian language proficiency. The participants were the bilingual elementary school students -the fifth-to eighth-graders coming from four Italian schools in Rijeka, Croatia. In addition to measure of reading comprehension, Metacomprehension test (Pazzaglia, Beni and Cristante, 1994) and cloze-task, as a measure of comprehension monitoring skill, as well as Strategic reading questionnaire (Kolic-Vehovec & Bajsanski, 2001), as a self-report measure of strategic reading, were applied. Questionnaire of Italian language use and perceived proficiency in Italian language was also applied. The difference in age of second language acquisition before the start of schooling was not the crucial determinant of later language proficiency. The bilingual students in the higher elementary school grades, who are more proficient in Italian, have better metacognitive reading skills than the less proficient students.
TL;DR: These findings imply that molecular mechanisms have evolved during mammalian evolution to strongly guard against potential heterozygosity for ribosomal protein genes.
Abstract: The capacity to detect and appropriately respond to many different stresses that interfere with functional homeostasis is essential for survival. Recent evidence suggests that the nucleolus, the site of ribosome biogenesis, plays a critical role in sensing and responding to both external and internal stresses. To understand these processes, we have recently used a genetically defined in vivo mouse model in which ribosome biogenesis could be manipulated during oogenesis and embryo development. In these mice ribosomal biosynthesis is impaired by a conditional deletion of one allele of the gene encoding 40S ribosomal protein S6. Embryos from these animals fail during gastrulation, apparently due to a p53-dependent checkpoint being triggered, rather than a deficit in translational capacity. These findings imply that molecular mechanisms have evolved during mammalian evolution to strongly guard against potential heterozygosity for ribosomal protein genes.
TL;DR: Robust intrapulmonary replication of the wild-type strain of L. pneumophila in susceptible A/J mice is associated with late-stage Dot/Icm-dependent pulmonary apoptosis and alveolar inflammation and caspase-3 is not activated at any stage of infection.
Abstract: The Dot/Icm system of Legionella pneumophila triggers activation of caspase-3 during early stages of infection of human macrophages, but apoptosis is delayed until late stages of infection. During early stages of infection of mouse macrophages, the organism triggers rapid caspase-1-mediated cytotoxicity, which is mediated by bacterial flagellin. However, it is not known whether caspase-1 is triggered by L. pneumophila in human macrophages or whether caspase-3 is activated in permissive or nonpermissive mouse macrophages. Using single-cell analyses, we show that the wild-type strain of L. pneumophila does not trigger caspase-1 activation throughout the intracellular infection of human monocyte-derived macrophages (hMDMs), even when the flagellated bacteria escape into the cytoplasm during late stages. Using single-cell analyses, we show that the Dot/Icm system of L. pneumophila triggers caspase-3 but not caspase-1 within permissive A/J mouse bone marrow-derived primary macrophages by 2 to 8 h, but apoptosis is delayed until late stages of infection. While L. pneumophila triggers a Dot/Icm-dependent activation of caspase-1 in nonpermissive BALB/c mouse-derived macrophages, caspase-3 is not activated at any stage of infection. We show that robust intrapulmonary replication of the wild-type strain of L. pneumophila in susceptible A/J mice is associated with late-stage Dot/Icm-dependent pulmonary apoptosis and alveolar inflammation. In the lungs of nonpermissive BALB/c mice, L. pneumophila does not replicate and does not trigger pulmonary apoptosis or alveolar inflammation. Thus, similar to hMDMs, L. pneumophila does not trigger caspase-1 but triggers caspase-3 activation during early and exponential replication in permissive A/J mouse-derived macrophages, and apoptosis is delayed until late stages of infection. The Dot/Icm type IV secretion system is essential for pulmonary apoptosis in the genetically susceptible A/J mice.
TL;DR: Results suggest that decidual natural killer cells, cultured in DMC for 18h, have the characteristics of lymphokine-activated killer (LAK) cells and are able to use efficiently both the perforin and the FasL cytolytic pathways.
TL;DR: There were no significant differences between groups in the intensity of traumatization, severity of PTSD symptoms, and the frequency of depression; however, there was one exception: severity of hyperarousal symptoms was positively correlated with occurrence of psychotic symptoms.
Abstract: The presence of psychotic symptoms in post-traumatic stress disorder (PTSD) has already been recognized. Using the Structured Clinical Interview Diagnostic and Statistical Manual, we searched for and assessed psychotic symptoms in 91 males suffering from combat-related PTSD. Hallucinations and delusions were present in 20% of patients. We divided all patients into three groups: the group with hallucinations and delusions, the group without these symptoms, and the group with “subthreshold” psychotic symptoms. Using the Harvard Trauma Questionnaire, Clinician-Administered PTSD Scale, and Structured Clinical Interview Diagnostic and Statistical Manual, we investigated differences between groups in the intensity of traumatization, severity of PTSD symptoms, and the frequency of depression. There were no significant differences between groups; however, there was one exception: severity of hyperarousal symptoms was positively correlated with occurrence of psychotic symptoms.
TL;DR: It is concluded that despite flagellation, infection by L. longbeachae is independent of polymorphism in the naip5 allele and L.LongBeachae does not trigger the activation of caspase 1, caspas 3, or late-stage apoptosis in mouse and human macrophages.
Abstract: Legionella longbeachae belongs to the family Legionellaceae, which causes a severe and fatal pneumonia known as Legionnaires' disease. In the United States, more than 90% of cases of Legionnaires' disease are caused by Legionella pneumophila (6). Interestingly, the most predominant species responsible for Legionnaires' disease in Western Australia is L. longbeachae (15). In addition, infection due to L. longbeachae has been reported in New Zealand, Germany, Japan, Denmark, Sweden, Canada, and The Netherlands. Unlike L. pneumophila, which inhabits mostly aquatic environments, L. longbeachae is commonly isolated from moist potting soil (29). In aquatic environments, amoeba serves as a reservoir for the amplification and dissemination of L. pneumophila and is considered the natural host for the bacterium (34). In addition, amoeba has been shown to resuscitate viable nonculturable L. pneumophila after disinfection by biocides, which may account for the reemergence of Legionella in water systems after disinfection (24).
L. pneumophila replicates in alveolar macrophages, which is necessary for the manifestation of Legionnaires' disease. After phagocytosis, L. pneumophila is localized in a unique phagosome that is isolated from the endocytic pathway (26, 41, 43). The L. pneumophila-containing phagosome excludes endocytic markers, including the lysosome-associated membrane glycoproteins lysosome-associated membrane protein 1 (LAMP-1) and LAMP-2 as well as the lysosomal acid protease cathepsin D (10). While the L. pneumophila-containing phagosome does not interact with the dynamic endocytic traffic, the L. longbeachae-containing phagosome interacts with the endocytic traffic and its biogenesis exhibits some maturation within the endocytic pathway (5). Recent studies have shown that within human macrophages, the L. longbeachae-containing phagosome is trafficked into a nonacidified late endosome-like phagosome that acquires the LAMPs and the mannose-6-phosphate receptor late endosomal markers but excludes the vacuolar ATPase proton pump and lysosomal markers (5). In addition, the L. longbeachae-containing phagosome is remodeled by the rough endoplasmic reticulum and bacterial replication occurs within the rough endoplasmic reticulum-remodeled late endosome-like phagosomes (5). Thus, there is a divergence in the mechanisms of pathogenesis of L. longbeachae and L. pneumophila in human macrophages (5). Further studies are needed to dissect further the host-parasite interaction of L. longbeachae, which is lagging behind that of most other intracellular pathogens, including the closely related species L. pneumophila.
Many intracellular pathogens, including L. pneumophila, have been shown to modulate the intrinsic and extrinsic apoptotic pathways of apoptosis that converge on the activation of caspase 3, resulting in apoptosis/programmed cell death (20). L. pneumophila induces the activation of caspase 3 in human macrophages during early stages of infection, which is thought to be essential for evasion of vesicle traffic, since inhibition of caspase 3 in human macrophages results in fusion of the phagosomes to lysosomes (18, 35). The activation of caspase 3 and the subsequent isolation of the phagosome from the endocytic pathway are mediated by the Dot/Icm type IV secretion system (47). Although caspase 3 is induced robustly during early stages of infection in human macrophages, apoptosis is not triggered until late stages of infection, concomitant with the termination of intracellular replication (2, 3, 35). The delay in apoptosis is associated with the induction of antiapoptotic signaling through the activation of NF-κB-dependent and -independent pathways (3, 30). In contrast, caspase 3 is not activated and is not required for the intracellular infection of mouse-derived macrophages (36, 45). Whether L. longbeachae also triggers caspase 3 and subsequent apoptosis in human macrophages is not known.
Among inbred mouse strains, A/J is the only inbred mouse strain susceptible to infection by L. pneumophila, while all the other strains are resistant (31). In contrast, many inbred strains of mice are susceptible to infection by many Legionella species (31). Only one study of permissiveness of mouse macrophages in vitro to L. longbeachae has been reported using a single isolate and indicated that the isolate replicates in both A/J and C57BL/6 thioglycolate-elicited mouse peritoneal macrophages, but whether the growth kinetics are similar to those of L. pneumophila is not known (27). Whether L. longbeachae can replicate in mouse lungs in vivo and whether mice are a suitable animal model for L. longbeachae are not known. The genetic susceptibility of mice has been attributed to a polymorphism in the neuronal apoptosis inhibitory protein 5 (naip5)-birc1e gene (13). At least eight murine homologues of naip genes have been identified (25), and naip5 has been identified as the gene responsible for the differential susceptibilities of A/J mice to L. pneumophila infection (13). The family of Naips is expressed abundantly in macrophage-rich tissues in mice, and their collective expression is increased after phagocytosis by murine macrophages (14), but whether Naip5 is one of the induced Naips is not known. The differential susceptibilities of different inbred mouse strains to infection by L. pneumophila are due to the rapid activation of caspase 1 in C57BL/6 versus A/J mice, resulting in early macrophage pyropoptosis-mediated cell death in C57BL/6 mice (36, 45). The L. pneumophila product that is responsible for the activation of caspase 1 is flagellin, but it is not known how Naip5 contributes to the process (36). Whether L. pneumophila triggers caspase 1 activation in human macrophages is not known, and whether L. longbeachae is capable of activating caspase 1 in mouse or human macrophages is also not known.
Some Naips have been shown to possess antiapoptotic activity (40) due to inhibition of caspase 3, caspase 7, and caspase 9 (17). The role of Naip5 in the activation of caspase 3 and apoptosis has not been determined, although it has been shown that the differential susceptibilities of mice to L. pneumophila are not related to the activation of caspase 3 (36, 45).
Here, we show that polymorphism of the naip5 allele does not play a role in the susceptibility of inbred mouse strains to infection by L. longbeachae. Both in vitro and in vivo studies show that L. longbeachae replicates efficiently in bone marrow-derived macrophages and in the lungs of A/J, C57BL/6, and BALB/c mice. In addition, we show that the induction of naip5 transcription in both L. pneumophila- and L. longbeachae-infected A/J mouse macrophages is less compared to that in C57BL/6 mice. We show that unlike what was observed with L. pneumophila, caspase 3 activation and late-stage apoptosis are triggered only at very low levels in both mouse and human macrophages infected by L. longbeachae. Flagellated L. longbeachae does not trigger caspase 1-mediated pyropoptosis in mouse macrophages, which correlates with the lack of detectable pore-forming activity in this species. Neither species activates caspase 1 in human macrophages.