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Flegr, J.

Publications and source records attributed to Flegr, J..

18 recordsLinked to original sources

A new and highly effective method for predicting T-cell response targets implemented on SARS-CoV-2 data

Computational T-cell epitope prediction is essential in many immunological projects, including the development of vaccines. T-cells of immunocompetent vertebrate hosts can recognize as non-self only peptides which are present in the parasites proteins and absent in the hosts proteins. This basic principle allows us to predict which peptides can elicit T-cells response. We built on the fact that the specificity of T-cells reacting to SARS-CoV-2 antigens has been recently mapped in detail. Using Monte Carlo tests, we found that empirically confirmed peptides that stimulate T-cells contain an increased fraction of pentapeptides, hexapeptides, and heptapeptides which are not found in the human proteome (p < 0.0001). Similarly, hexapeptides absent in human proteins were overrepresented in peptides that elicited T-cell response in a published empirical study (p = 0.027). The new theory-based method predicted T-cell immunogenicity of SARS-CoV-2 peptides four times more effectively than current empirically based methods.

immunology↗

Presence of Toxoplasma gondii tissue cysts in human semen

Toxoplasma gondii is a widely prevalent protozoan parasite in human populations. This parasite is thought to be primarily transmitted through undercooked meat and contamination by cat feces. Here, we demonstrate that Toxoplasma gondii cysts can be found within human semen, thus suggesting a potential for sexual transmission. We visualized Toxoplasma gondii cysts in ejaculates of immune-competent and latently infected human volunteers. We confirmed the encystment by probing transcription of a bradyzoite-specific gene in these structures. These observations extend previous observations of the parasite in semen of several non-human host species, including rats, dogs, and sheep. Toxoplasma gondii infection is a clinically significant infection, in view of its high prevalence, its purported role in neuropsychiatric disorders such as schizophrenia, as well as in the more serious form of congenital toxoplasmosis. Our demonstration of intact Toxoplasma gondii cysts in the ejaculate supports the possibility of sexual transmission of the parasite and provides an impetus for further investigations. ImportanceToxoplasma gondii is recognized as one of the five infections that can harm fetal health. There is also emerging evidence that toxoplasmosis is related to the development of neuropsychiatric disorders. In this context, the current report includes visual evidence of Toxoplasma gondii cyst presence in the semen of human males. It is thus plausible that this clinically significant infection can be sexually transmitted. The existence of sexual transmission in a population, and its relative importance vis-a-vis other transmission routes, remains undetermined. These possibilities are of acute relevance to human health in the context of sexual health and pregnancy management.

microbiology↗

Increased calcidiol level in redhaired people: Could redheadedness be an adaptation to temperate climate?

About 1-2% of European population are redhaired, meaning they synthesize more pheomelanin than eumelanin, the main melanin pigment. Several mutations could be responsible for this phenotype. It has been suggested that corresponding mutations spread in Europe due to a founder effect shaped either by a relaxation of selection for dark, UV-protective phenotypes or by sexual selection in favor of rare phenotypes. In our study, we investigated the levels of vitamin D precursor calcidiol and folic acid in the blood serum of 73 redhaired and 130 non-redhaired individuals. In redhaired individuals, we found higher calcidiol concentrations and approximately the same folic acid concentrations as in non-redhaired subjects. Calcidiol concentrations correlated with the intensity of hair redness measured by two spectrophotometric methods and estimated by participants themselves and by independent observers. In non-redhaired individuals, calcidiol levels covaried with the amount of sun exposure and intensity of suntan while in redhaired individuals, this was not the case. It suggests that increased calcidiol levels in redhaired individuals are due to differences in physiology rather than in behavior. We also found that folic acid levels increased with age and the intensity of baldness and decreased with the frequency of visiting tanning salons. Our results suggest that the redhaired phenotype could be an evolutionary adaptation for sufficient photosynthesis of provitamin D in conditions of low intensity of UV-B radiation in central and northern parts of Europe.

evolutionary biology↗

Friends with malefit. The effects of keeping dogs and cats, sustaining animal-related injuries and Toxoplasma infection on health and quality of life

Many studies show that keeping cats and dogs has a positive impact on humans physical and mental health and quality of life. The existence of this \"pet phenomenon\" is now widely discussed because other studies performed recently have demonstrated a negative impact of owning pets or no impact at all. The main problem of many studies was the autoselection - participants were informed about the aims of the study during recruitment and later likely described their health and wellbeing according to their personal beliefs and wishes, not according to their real status. To avoid this source of bias, we did not mention pets during participant recruitment and hid the pet-related questions among many hundreds of questions in an 80-minute Internet questionnaire. Results of our study performed on a sample of on 10,858 subjects showed that liking cats and dogs has a weak positive association with quality of life. However, keeping pets, especially cats, and even more being injured by pets, were strongly negatively associated with many facets of quality of life. Our data also confirmed that infection by the cat parasite Toxoplasma had a very strong negative effect on quality of life, especially on mental health. However, the infection was not responsible for the observed negative effects of keeping pets, as these effects were much stronger in 1,527 Toxoplasma-free subjects than in the whole population. Any cross-sectional study cannot discriminate between a cause and an effect. However, because of the large and still growing popularity of keeping pets, the existence and nature of the reverse pet phenomenon deserve the outmost attention.

animal behavior and cognition↗

New approach and new program for analyses of false negatives-contaminated data in medicine and biology

BackgroundNo serological assay has 100% sensitivity. Statistically, the concentration of specific antibodies against antigens of parasites decreases with the duration of infection. This can result in false negative outputs of diagnostic tests for the subjects with old infectiong, e.g., for individuals infected in childhood. When a property of seronegative and seropositive subjects is compared under these circumstances, the statistical tests can detect no significant difference between these two groups of subjects, despite the fact that infected and noninfected subjects differ. When the effect of the infection has a cumulative character and subjects with an older infection (potential false negatives) are affected to a greater degree, we can even get paradoxical result of the comparison - the seronegative subjects have on average lower value of certain traits, e.g. IQ, despite the infection having a negative effect on the trait. A permutation test for the contaminated data, implemented, e.g., in the program Treept or available as a comprehensibly commented R function in the supplement of this paper, can be used to reveal and to eliminate the effect of false negatives.\n\nMethodsWe used a Monte Carlo simulation in the program R to show that the permutation test implemented in the programs Treept and PTPT is a conservative test.\n\nResultsWe showed that the test could provide false negative but not false positive results if the studied population contains no subpopulation of false negative subjects. We also introduced R version of the test expanded by skewness analysis, which helps to estimate the proportion of false negative subjects based on the assumption of equal data skewness in groups of healthy and infected individuals.\n\nConclusionsBased on the results of simulations and our experience with empirical studies we recommend the usage of permutation test for contaminated data whenever seronegative and seropositive individuals are compared.

epidemiology↗

Maternal RhD heterozygous genotype is associated with male biased secondary sex ratio

The results of previous studies overwhelmingly suggest that RhD positive heterozygotes express better health status than Rh positive homozygous, especially in RhD negative subjects. This also applies to pregnant women. According to the Trivers-Willard hypothesis, women in better physical condition should have a male-skewed sex ratio. The aim of the present study was to test the hypothesis that RhD positive heterozygous mothers give birth to more sons than daughters. In the present cross-sectional study, we analysed data from 5,655 women who have given birth in the General University Hospital in Prague, Czech Republic between 2008-2012. Clinical records comprised maternal weight before pregnancy, number of previous deliveries, sex of the newborn, maternal RhD phenotype, and RhD phenotype of the newborn. Secondary sex ratio was significantly higher (P=0.028) in RhD positive mothers who had RhD negative newborns, i.e. in heterozygotes (SR=1.23), than in RhD positive mothers who had RhD positive newborns, i.e. in a mixed population of heterozygotes and homozygotes (SR=1.00), especially in primiparous women (P=0.013; SR=1.37 and 0.99 resp.). In line with the Trivers-Willard effect, RhD maternal heterozygous genotype is associated with male biased secondary sex ratio. The results supported the hypothesis that RhD polymorphism may be maintained due to heterozygote health advantages.

evolutionary biology↗

Perinatal outcomes, maternal age, parity and fetal sex - searching for the \"optimal\" maternal age

BackgroundMaternal age, parity and fetal sex are each known to affect obstetric and birth outcomes. The objective of the present study was to investigate the influence of the combination of maternal age, parity and fetal sex on outcomes of pregnancies._The aim of the study was to analyze the influence of maternal age on perinatal outcomes in both primiparous and multiparous women with different fetal sex.\n\nMethodsThe cross-sectional study was performed on data from 11,780 women, who have given birth at the General University Hospital in Prague, Czech Republic between 2008-2012.\n\nResultsMaternal age significantly (P<0.01) influenced pregnancy weight gain, duration of pregnancy, birth weight and birth length. Primiparous women with female newborns aged [&le;]19 had higher rates of preterm delivery than comparable women 20-39 (P=0.012). Similarly, women with male newborns aged [&ge;]40 had higher rates of preterm delivery than comparable women 20-39 (P=0.003). Women aged [&le;]24 expressed higher rates of low birth weight than women aged >24 (P<0.001), regardless of parity and fetal sex. The older ([&ge;]35) primiparous women with male newborns expressed a higher incidence of macrosomia (P=0.021) compared to other groups of women. The probability of caesarean delivery increased with age (P<0.001) and it was significantly affected by the parity and sex of the newborn with higher rates of caesarean section in primiparous women as well as in mothers carrying male fetuses.\n\nConclusionsOur results indicate that \"optimal\" maternal age without obstetrics and birth complications is 25-34 years, older age is associated with increased complications with a male fetus, especially in primiparous women. Our data suggests that not just the age of women, but the combination of age, parity, and fetal sex should be taken into consideration during assessment of health risks of pregnancy.

epidemiology↗

Differences in cognitive functions between cytomegalovirus-infected and cytomegalovirus-free university students: a case-control study

Cytomegalovirus (CMV) is the herpetic virus, which infects 45-100% people worldwide. Many reports suggest that CMV could impair cognitive functions of infected subjects. Here we searched for indices of effects of CMV on infected subjects' intelligence and knowledge. The Intelligence Structure Test I S T 2000 R was used to compare IQ of 148 CMV infected and 135 CMV free university students. Infected students expressed higher intelligence. Paradoxically, their IQ decreased with decreasing concentration of anti CMV antibodies, which can be used, statistically, as a proxy of the time passed from the moment of infection in young subjects when the age of subjects is statistically controlled. The paradox of seemingly higher intelligence of CMV infected subjects could be explained by the presence of the subpopulation of about 5-10 % CMV positive individuals in the population of "CMV negative students". These false negative subjects had probably not only the oldest infections and therefore the lowest concentration of anamnestic antibodies, but also the lowest intelligence among the infected students. Prevalence of CMV infection in all countries is very high, approaching sometimes 90 %. Therefore, the total impact of CMV on human intelligence may be large.

neuroscience↗

Depressiveness and Neuroticism in Bartonella Seropositive and Seronegative Subjects - Preregistered Case-Controls Study

Several recent studies have demonstrated the association of cat-related injuries with major depression and with depressiveness in the general population. It was suggested that cat-scratch disease, the infection with the bacterium Bartonella henselae, can be responsible for the observed association. However, no direct evidence for the role of the Bartonella infection in this association has been published until now. In this preregistered case-controls study performed on 250 healthy subjects tested earlier for the presence of anti-Toxoplasma IgG antibodies, we searched for the positive association between presence of anamnestic anti-Bartonella IgG antibodies and depressiveness measured with Beck II inventory, depression subscale of neuroticism measured with N-70 questionnaire, and self-reported health problems. We found that that Bartonella-seropositivity was positively correlated with Beck depression only in Toxoplasma-seronegative men and negatively correlated with health in Toxoplasma-seronegative women. Bartonella seropositivity expressed protective effects against Toxoplasma seropositivity-associated increased neuroticism in men while Toxoplasma-seropositivity expressed protective effects against Bartonella seropositivity-associated health problems in women. A comparison of the patterns of association of mental and physical health problems with Bartonella seropositivity and with reported cat-related injury suggests that different factor, possibly infection with different pathogen transmitted by cat related-injuries than the Bartonella henselae, is responsible for the observed association of cat related-injuries with depressiveness and major depression. The existence of complex interactions between Bartonella seropositivity, Toxoplasma seropositivity, and sex also suggest that the effect of symbionts on the host's phenotype must by always studied in the context of other infections, and separately for men and women.

neuroscience↗

Lower performance of Toxoplasma-infected, Rh-negative subjects in the weight holding and hand-grip tests

Toxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.

pathology↗

Toxoplasmosis, but not borreliosis, is associated with psychiatric disorders: A cross-sectional survey on 46 thousand of subjects

Infection by the parasite Toxoplasma, which affects about 33% of world population, is associated with increased risk of several mental health disorders, the most strongly with schizophrenia. It is unknown whether toxoplasmosis really plays a substantial role in the etiopathogenesis of these disorders and whether schizophrenia is associated with this infection the most strongly, or whether this association has just been the most intensively studied for historical reasons. We used the data from 3,440 and 7,800 subjects tested for toxoplasmosis and borreliosis, respectively, who took part in an internet survey, for searching in the associations of these infections with 22 mental health disorders and other indices of impaired mental health. The typical symptom associated with toxoplasmosis was anxiety, and the typical toxoplasmosis-associated disorders were autism (OR=4.86), schizophrenia (OR=3.34), attention deficit hyperactivity disorder (OR=3.02), Asperger syndrome (OR=2.49), antisocial personality disorder (OR=1.81), OCD (OR=1.69), and anxiety disorder (OR=1.57). Borreliosis was associated only with symptoms of depression and with major depression (OR=1.65). The negative effects of borreliosis were detectable only in the Toxoplasma-infected subjects. Toxoplasmosis could play a substantial role in the etiopathogenesis of mental health disorders and its association with schizophrenia is the second strongest association, after autism.

neuroscience↗

Effects of latent toxoplasmosis on olfactory functions of men and women

The prevalence of toxoplasmosis is higher in schizophrenics than in the general population. It has been suggested that certain symptoms of schizophrenia, including changes in olfactory functions, are in fact symptoms of toxoplasmosis that can be easily detected in schizophrenics only due to the increased prevalence of toxoplasmosis in this population. Schizophrenics have impaired identification of odors and lower sensitivity of odor detection. Here we searched for differences in olfactory functions between 62 infected and 61 noninfected non-schizophrenic subjects. The infected men scored better in the standard odor-identification test. The infected women rated all smells as more intensive while the infected men rated nearly all smells as less intensive. Infected women rated the pleasantness of the smell of undiluted cat urine as higher than the non-infected women and the opposite was true for the men (the opposite direction shifts in men and women were described earlier for highly diluted cat urine). Toxoplasmosis had no effect on the rated pleasantness of the smell of other stimuli. Our results suggest that latent toxoplasmosis is associated with changes in the olfactory functions in humans; however, the observed changes differ from those observed in schizophrenics.\n\nKey findingsO_LIInfected men but not women show better odor identification ability than the non-infected controls.\nC_LIO_LIThe infected women rated all smells as more and men as less intensive than the controls.\nC_LIO_LIThe infected women rated smell of cat urine as more and men as less pleasurable than the controls.\nC_LIO_LIToxoplasmosis had no effect on the rated pleasantness of the smell of other stimuli.\nC_LIO_LIWe found no new evidence for the toxoplasmosis hypothesis of schizophrenia.\nC_LI

animal behavior and cognition↗

Stability-based sorting: The forgotten process behind (not only) biological evolution

Natural selection is considered to be the main process that drives biological evolution. It requires selected entities to originate dependent upon one another by the means of reproduction or copying, and for the progeny to inherit the qualities of their ancestors. However, natural selection is a manifestation of a more general persistence principle, whose temporal consequences we propose to name \"stability-based sorting\" (SBS). Sorting based on static stability, i.e., SBS in its strict sense and usual conception, favours characters that increase the persistence of their holders and act on all material and immaterial entities. Sorted entities could originate independently from each other, are not required to propagate and need not exhibit heredity. Natural selection is a specific form of SBS--sorting based on dynamic stability. It requires some form of heredity and is based on competition for the largest difference between the speed of generating its own copies and their expiration. SBS in its strict sense and selection thus have markedly different evolutionary consequences that are stressed in this paper. In contrast to selection, which is opportunistic, SBS is able to accumulate even momentarily detrimental characters that are advantageous for the long-term persistence of sorted entities. However, it lacks the amplification effect based on the preferential propagation of holders of advantageous characters. Thus, it works slower than selection and normally is unable to create complex adaptations. From a long-term perspective, SBS is a decisive force in evolution--especially macroevolution. SBS offers a new explanation for numerous evolutionary phenomena, including broad distribution and persistence of sexuality, altruistic behaviour, horizontal gene transfer, patterns of evolutionary stasis, planetary homeostasis, increasing ecosystem resistance to disturbances, and the universal decline of disparity in the evolution of metazoan lineages. SBS acts on all levels in all biotic and abiotic systems. It could be the only truly universal evolutionary process, and an explanatory framework based on SBS could provide new insight into the evolution of complex abiotic and biotic systems.

evolutionary biology↗

The mismeasure of (obese) man - body mass index is an inadequate indicator of body condition

The body mass index (BMI), recommended also by the World Health Organization, is currently used as the leading body condition indicator in clinical and epidemiological studies and has become popular among the general public. Here we provide evidence of a systematic bias in BMI, showing that BMI is dependent on body height. As a result, shorter persons have a greater chance of being classified as underweight, while taller persons as overweight, even if they have identical nutritional status. Use of BMI should be thus abandoned in diagnosis as well as in clinical and experimental studies.

physiology↗

General Environmental Heterogeneity As The Explanation Of Sexuality? Comparative Study Shows That Ancient Asexual Taxa Are Associated With Both Biotically And Abiotically Homogeneous Environments

Ecological theories of sexual reproduction assume that sexuality is advantageous in certain conditions, for example, in biotically or abiotically more heterogeneous environments. Such theories thus could be tested by comparative studies. However, the published results of these studies are rather unconvincing. Here we present the results of a new comparative study based solely on the ancient asexual clades. The association with biotically or abiotically homogeneous environments in these asexual clades was compared with the same association in their sister, or closely related, sexual clades. Using the conservative definition of ancient asexuals (i.e. age > 1 million years), we found six pairs for which relevant ecological data are available. The difference between the homogeneity type of environment associated with the sexual and asexual species was then compared in an exact binomial test. Based on available literature, the results showed that the vast majority of ancient asexual clades tend to be associated with biotically or abiotically, biotically, and abiotically more homogeneous environments than their sexual controls. In the exploratory part of the study, we found that the ancient asexuals often have durable resting stages, enabling life in subjectively homogeneous environments, live in the absence of intense biotic interactions, and are very often sedentary, inhabiting benthos and soil. The consequences of these findings for the ecological theories of sexual reproduction are discussed.

evolutionary biology↗

Physical And Mental Health Status In Toxoplasma-Infected Women Before And Three Years After They Learn About Their Infection: The Role Of Rh Factor

Latent toxoplasmosis is known to be associated with specific changes in animal and human behavior and human personality. Many toxoplasmosis-associated shifts, such as an extroversion-introversion shift or a trust -suspicion shift, go in opposite directions in men and women. The stress coping hypothesis suggests that such behavioral effects of toxoplasmosis are side effects of chronic stress caused by lifelong parasitosis and associated health disorders. Several studies have searched for, and typically found, indices of impaired health in infected subjects. However, subjects were always aware of their toxoplasmosis status, which could influence obtained data and cause false-positive results of the studies. Here we searched for differences in physical and mental health status among 39 Toxoplasma-infected and 40 Toxoplasma-free female university students who completed identical questionnaires (N-70, and anamnestic questionnaire), before and 3 years after they were informed of their toxoplasmosis status. Our results showed that infected women showed indices of poorer health status, not only after, but also before they were informed of their infection. In accordance with previously published data, these indices were more numerous and stronger in Rh-negative than in Rh-positive women. Present results suggest that observed indices of poorer health and symptoms of chronic stress in Toxoplasma-infected subjects are real. Due to its high (30%) prevalence, toxoplasmosis could represent an important factor for public health.

neuroscience↗

On The Advantages Of Evolutionary Passivity In Fluctuating Environments: Could Sex Be The Preadaptation For The Stability-Based Sorting?

The ability of organisms to adaptively respond to environmental changes (evolvability) is usually considered to be an important advantage in interspecific competition. It has been suggested, however, that evolvability could be a double-edged sword that could present a serious handicap in fluctuating environments. The authors of this counterintuitive idea have published only verbal models to support their claims.\n\nHere we present the results of individual-based stochastic modelling of competition between two asexual species differing only by their evolvability. They show that, in changeable environments, less evolvable species could outperform their more evolvable competitors in a broad area of a parameter space, regardless of whether the conditions fluctuated periodically or aperiodically. Highly evolvable species prospered better nearly all the time; however, they sustained a higher probability of extinction during rare events of the rapid transient change of conditions.\n\nOur results offer an explanation of why sexually reproducing species, with their reduced capacity to respond adaptively to local or temporal environmental changes, prevail in most eukaryotic taxa in nearly all biotopes on the surface of Earth. These species may suffer several important disadvantages in direct competitive battles with asexual species; however, they might win in changeable environments in the more important sorting-according-to-stability war.

evolutionary biology↗

Health Status By Gender, Hair Color, And Eye Color: Red-Haired Women Are The Most Divergent

BackgroundRed hair is associated with pain sensitivity, and more so in women than in men. Hair redness may thus interact with a female-specific factor. We tested this hypothesis on a large sample of Czech and Slovak respondents. They were asked about the natural redness and darkness of their hair, their natural eye color, their physical and mental health (24 categories), and other personal attributes (height, weight, number of children, lifelong number of sexual partners, frequency of smoking).\n\nResultsWe found that red-haired women did worse than other women in ten health categories and better in only three. In particular, they were more prone to colorectal, cervical, uterine, and ovarian cancer. Cancer risk increased steadily with increasing hair redness except for the reddest shade. Red-haired men showed a balanced pattern of health effects, doing better than other men in three categories and worse in three. Number of children was the only category where both male and female redheads did better than other respondents. We also confirmed earlier findings that red hair is naturally more frequent in women than in men.\n\nConclusionRed-haired women had higher fecundity and sexual attractiveness, but this selective advantage seems offset by worse health outcomes and therefore lower viability. The resulting equilibrium between these two counterbalancing forces might explain why red hair has remained less common than other hair and eye colors. Of the new hair and eye colors, red hair diverges the most from the ancestral state of black hair and brown eyes. It is the most sexually dimorphic variant, not only in population frequency but also in health outcomes. This sexual dimorphism seems to have resulted from a selection pressure that acted primarily on early European women and which led to a general and apparently rapid diversification of hair and eye colors.

evolutionary biology↗