Cancer risk across mammals.

Cancer is a ubiquitous disease of metazoans, predicted to disproportionately affect larger, long-lived organisms owing to their greater number of cell divisions, and thus increased probability of somatic mutations1,2. While elevated cancer risk with larger body size and/or longevity has been documented within species3-5, Peto's paradox indicates the apparent lack of such an association among taxa6. Yet, unequivocal empirical evidence for Peto's paradox is lacking, stemming from the difficulty of estimating cancer risk in non-model species. Here we build and analyse a database on cancer-related mortality using data on adult zoo mammals (110,148 individuals, 191 species) and map age-controlled cancer mortality to the mammalian tree of life. We demonstrate the universality and high frequency of oncogenic phenomena in mammals and reveal substantial differences in cancer mortality across major mammalian orders. We show that the phylogenetic distribution of cancer mortality is associated with diet, with carnivorous mammals (especially mammal-consuming ones) facing the highest cancer-related mortality. Moreover, we provide unequivocal evidence for the body size and longevity components of Peto's paradox by showing that cancer mortality risk is largely independent of both body mass and adult life expectancy across species. These results highlight the key role of life-history evolution in shaping cancer resistance and provide major advancements in the quest for natural anticancer defences.

Correlated evolution of oxidative physiology and MHC-based immunosurveillance in birds.

Maintenance and activation of the immune system incur costs, not only in terms of substrates and energy but also via collateral oxidative damage to host cells or tissues during immune response. So far, associations between immune function and oxidative damage have been primarily investigated at intra-specific scales. Here, we hypothesized that pathogen-driven selection should favour the evolution of effective immunosurveillance mechanisms (e.g. major histocompatibility complex, MHC) and antioxidant defences to mitigate oxidative damage resulting from immune function. Using phylogenetically informed comparative approaches, we provided evidence for the correlated evolution of host oxidative physiology and MHC-based immunosurveillance in birds. Species selected for more robust MHC-based immunosurveillance (higher gene copy numbers and allele diversity) showed stronger antioxidant defences, although selection for MHC diversity still showed a positive evolutionary association with oxidative damage to lipids. Our results indicate that historical pathogen-driven selection for highly duplicated and diverse MHC could have promoted the evolution of efficient antioxidant mechanisms, but these evolutionary solutions may be insufficient to keep oxidative stress at bounds. Although the precise nature of mechanistic links between the MHC and oxidative stress remains unclear, our study suggests that a general evolutionary investment in immune function may require co-adaptations at the level of host oxidative metabolism.

Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study.

Chronically high blood glucose levels (hyperglycaemia) can compromise healthy ageing and lifespan at the individual level. Elevated oxidative stress can play a central role in hyperglycaemia-induced pathologies. Nevertheless, the lifespan of birds shows no species-level association with blood glucose. This suggests that the potential pathologies of high blood glucose levels can be avoided by adaptations in oxidative physiology at the macroevolutionary scale. However, this hypothesis remains unexplored. Here, we examined this hypothesis using comparative analyses controlled for phylogeny, allometry and fecundity based on data from 51 songbird species (681 individuals with blood glucose data and 1021 individuals with oxidative state data). We measured blood glucose at baseline and after stress stimulus and computed glucose stress reactivity as the magnitude of change between the two time points. We also measured three parameters of non-enzymatic antioxidants (uric acid, total antioxidants and glutathione) and a marker of oxidative lipid damage (malondialdehyde). We found no clear evidence for blood glucose concentration being correlated with either antioxidant or lipid damage levels at the macroevolutionary scale, as opposed to the hypothesis postulating that high blood glucose levels entail oxidative costs. The only exception was the moderate evidence for species with a stronger stress-induced increase in blood glucose concentration evolving moderately lower investment into antioxidant defence (uric acid and glutathione). Neither baseline nor stress-induced glucose levels were associated with oxidative physiology. Our findings support the hypothesis that birds evolved adaptations preventing the (glyc)oxidative costs of high blood glucose observed at the within-species level. Such adaptations may explain the decoupled evolution of glycaemia and lifespan in birds and possibly the paradoxical combination of long lifespan and high blood glucose levels relative to mammals.

The effect of placentation type, litter size, lactation and gestation length on cancer risk in mammals.

Reproduction is a central activity for all living organisms but is also associated with a diversity of costs that are detrimental for survival. Until recently, the cost of cancer as a selective force has been poorly considered. Considering 191 mammal species, we found cancer mortality was more likely to be detected in species having large, rather than low, litter sizes and long lactation lengths regardless of the placentation types. However, increasing litter size and gestation length are not per se associated with an enhanced cancer mortality risk. Contrary to basic theoretical expectations, the species with the highest cancer mortality were not those with the most invasive (i.e. haemochorial) placentation, but those with a moderately invasive (i.e. endotheliochorial) one. Overall, these results suggest that (i) high reproductive efforts favour oncogenic processes' dynamics, presumably because of trade-offs between allocation in reproduction effort and anti-cancer defences, (ii) cancer defence mechanisms in animals are most often adjusted to align reproductive lifespan, and (iii) malignant cells co-opt existing molecular and physiological pathways for placentation, but species with the most invasive placentation have also selected for potent barriers against lethal cancers. This work suggests that the logic of Peto's paradox seems to be applicable to other traits that promote tumorigenesis.

Experimental evidence of dispersal of invasive cyprinid eggs inside migratory waterfowl.

Fish have somehow colonized isolated water bodies all over the world without human assistance. It has long been speculated that these colonization events are assisted by waterbirds, transporting fish eggs attached to their feet and feathers, yet empirical support for this is lacking. Recently, it was suggested that endozoochory (i.e., internal transport within the gut) might play a more important role, but only highly resistant diapause eggs of killifish have been found to survive passage through waterbird guts. Here, we performed a controlled feeding experiment, where developing eggs of two cosmopolitan, invasive cyprinids (common carp, Prussian carp) were fed to captive mallards. Live embryos of both species were retrieved from fresh feces and survived beyond hatching. Our study identifies an overlooked dispersal mechanism in fish, providing evidence for bird-mediated dispersal ability of soft-membraned eggs undergoing active development. Only 0.2% of ingested eggs survived gut passage, yet, given the abundance, diet, and movements of ducks in nature, our results have major implications for biodiversity conservation and invasion dynamics in freshwater ecosystems.

Sexual dimorphism in immune function and oxidative physiology across birds: The role of sexual selection.

Sex-specific physiology is commonly reported in animals, often indicating lower immune indices and higher oxidative stress in males than in females. Sexual selection is argued to explain these differences, but empirical evidence is limited. Here, we explore sex differences in immunity, oxidative physiology and packed cell volume of wild, adult, breeding birds (97 species, 1997 individuals, 14 230 physiological measurements). We show that higher female immune indices are most common across birds (when bias is present), but oxidative physiology shows no general sex-bias and packed cell volume is generally male-biased. In contrast with predictions based on sexual selection, male-biased sexual size dimorphism is associated with male-biased immune measures. Sexual dichromatism, mating system and parental roles had no effect on sex-specificity in physiology. Importantly, female-biased immunity remained after accounting for sexual selection indices. We conclude that cross-species differences in physiological sex-bias are largely unrelated to sexual selection and alternative explanations should be explored.

Transmissible cancer and the evolution of sex.

The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism's genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes.

Avian blood parasite richness decreases with major histocompatibility complex class I loci number.

Major histocompatibility complex (MHC) genes are among the most polymorphic in the vertebrate genome. The high allele diversity is believed to be maintained primarily by sexual and pathogen-mediated balancing selection. The number of MHC loci also varies greatly across vertebrates, most notably across birds. MHC proteins play key roles in presenting antigens on the cell surface for recognition by T cells, with class I proteins specifically targeting intracellular pathogens. Here, we explore the hypothesis that MHC class I diversity (measured as loci number) coevolves with haemosporidian parasite burden of the host. Using data on 54 bird species, we demonstrate that high-MHC class I diversity is associated with significantly lower richness of Plasmodium, Haemoproteus as well as overall haemosporidian parasite lineages, the former thus indicating more efficient protection against intracellular pathogens. Nonetheless, the latter associations were only detected when MHC diversity was assessed using cloning and not 454 pyrosequencing-based studies, nor across all genotyping methods combined. Our results indicate that high-MHC class I diversity might play a key role in providing qualitative resistance against diverse haemosporidian parasites in birds, but further clarification is needed for the origin of contrasting results when using different genotyping methods for MHC loci quantification.

Wing morphology, flight type and migration distance predict accumulated fuel load in birds.

Birds often accumulate large fat and protein reserves to fuel long-distance flights. While it is well known that species that fly the longest accumulate the largest amounts of fuel, considerable cross-species variation in fuel load is seen after controlling for overall migration distance. It remains unclear whether this variation can be explained by aerodynamic attributes of different species, despite obvious ecological and conservation implications. Here, we collected data on wing morphology, flight type, migration distance and fuel load from 213 European bird species and explored three questions: (1) does maximum fuel load relate to migration distance across species?; (2) does wing morphology, as described by wing aspect ratio and wing loading, influence maximum fuel load?; and (3) does flight type influence maximum fuel load? Our results indicate that maximum fuel load increases with migration across species, but residual variance is high. The latter variance is explained by aspect ratio and flight type, while wing loading and body mass explain little variance. Birds with slender wings accumulate less fuel than species with low wing aspect ratio when covering a similar migration distance. Continuously flapping species accumulate the largest amounts of fuel, followed by flapping and soaring species and flapping and gliding species, while the smallest fuel loads were observed in birds with passerine-type flight. These results highlight complex eco-evolutionary adaptations to migratory behaviour, pointing toward the importance of energy minimisation.

Word Use and Content Analysis of the First Verses of Six National Anthems: A Transcultural Aspect of Suicidal Behaviour.

BACKGROUND: Suicide is a major health concern worldwide, although suicide rates widely differ among different countries and cultures. Transcultural studies suggest that national anthems reflect national attitudes towards self-harming behaviour as well. Our aim was to analyse the linguistic characteristics of six national anthems, and compare these results with national suicide rates. METHODS: Word use assessment and content analysis of six national anthems were performed. RESULTS: In the anthems of countries with similar historical or cultural background, similar linguistic patterns were found in word use and in content. Anthems of countries with lower suicide rates tend to contain relatively more positive contents, emotions and intentions, while in the anthems of countries with higher suicide rates more ambivalence, denial, loss or even aggressive and self-destructive implications were found. CONCLUSION: This transcultural analysis strengthens previous data that anthems could be indicators for national attitudes toward self-harm.

Brain regions associated with visual cues are important for bird migration.

Long-distance migratory birds have relatively smaller brains than short-distance migrants or residents. Here, we test whether reduction in brain size with migration distance can be generalized across the different brain regions suggested to play key roles in orientation during migration. Based on 152 bird species, belonging to 61 avian families from six continents, we show that the sizes of both the telencephalon and the whole brain decrease, and the relative size of the optic lobe increases, while cerebellum size does not change with increasing migration distance. Body mass, whole brain size, optic lobe size and wing aspect ratio together account for a remarkable 46% of interspecific variation in average migration distance across bird species. These results indicate that visual acuity might be a primary neural adaptation to the ecological challenge of migration.

Physiological pace of life: the link between constitutive immunity, developmental period, and metabolic rate in European birds.

Constitutive innate immunity is the first lined of defence against infections, but the causes determining its variability among species are poorly understood. The pace of life hypothesis predicts that species with a fast speed of life, characterized by high energy turnover and short developmental time, invest relatively little in defence in favour of growth and early reproduction, whereas 'slow-living' species are predicted to invest more resources into costly defence. We conducted phylogenetic comparative analysis on 105 European bird species and determined that the number of leukocytes, and the levels of natural antibodies (NAbs) and complement, measured on adult birds, increased or tended to positively correlate with the length of incubation period. However, we found that the length of incubation and fledging periods have opposite effects on immune defence (i.e. immune parameters show a negative association with the length of fledging period). Our results suggest that the contrasting effects of the incubation and fledging periods are related to the timing of the development of immune cells and of NAbs and complement, which largely mature during the embryonic phase of development. In support of this hypothesis, we found that species with a long relative incubation period [i.e. whose total pre-fledging developmental time (incubation plus fledging) consists largely of the incubation period] invested more in constitutive innate immunity. Finally, in support of the pace of life hypothesis, for a subsample of 63 species, we found that the basal metabolic rate significantly or tended to negatively correlate with immune measures.

Feelings and motives underlying Machiavellian behavioural strategies; narrative reports in a social dilemma situation.

This study explored the reasons and motives underlying the decisions of individuals with strong Machiavellian attitudes (High Machs). One hundred and fifty undergraduate students completed the Mach-IV test, and their contributions to, financial success in and narrative reports of a public goods game were analysed. High Machs contributed less to the public good and gained more benefit than Low Machs. Analysis of the narrative reports showed that High Machs used significantly fewer verbs referring to emotional involvement and first person plural verb forms, than did Low Machs. This study confirmed previous findings that High Machs have a cool and rational character and a proself orientation and showed that their lack of group orientation may account for their low cooperation in social dilemmas. The results of narrative content analysis provide a new perspective on the motives and values behind High Machs' decisions and success in different fields of social life.

Temporal Recall Strategies in Rheumatoid Arthritis Patients' Emotionally Intense Life Events.

BACKGROUND: Rheumatoid arthritis (RA) patients often encounter psychological challenges due to chronic pain, fatigue, side effects of medications, and disability. This study examines the relationship between autobiographical narratives and recollection patterns in RA patients. We investigated how different recall strategies for positive life events affect the emotional processing of negative episodes. We hypothesized that vividly recalling positive life events provides psychological resources that support a more intense emotional elaboration of stressful memories, allowing individuals to delve deeper into negative life experiences. Additionally, we explored the impact of these perspectives on self-reported well-being and physical health, proposing that re-living positive events improves overall well-being. METHODS: We collected and analyzed high-point and low-point life-story episodes from 60 RA patients (85% female; age mean 61 ± 11 years; range 37-79) using episodic narrative interviews and the Narrative Categorical Content Analysis algorithm (NarrCat). Participants were categorized into 2 clusters based on their temporal perspective during high-point episodes: 25 used a Retrospective viewpoint, while 35 employed a Re-experiencing strategy. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and functioning was measured using the Health Assessment Questionnaire (HAQ). RESULTS: The Re-experiencing group, which was more likely to articulate their high-point episode in vivid and real-time narrative, used more psychological perspectives (U(58) = 223, p < 0.01) and showed heightened emotional frequency (U(58) = 280, p < 0.05; positive: U(58) = 328, p < 0.05; negative: U(58) = 278, p < 0.05) in low-point episodes. No significant difference emerged between the two groups regarding psychological state (anxiety, depressive symptoms) and physical impairment. CONCLUSIONS: Vividly recalling positive events may facilitate a deeper exploration of negative memories. The Re-experiencing group showed increased positive emotions during low points, suggesting better emotion regulation. However, no significant association was found between recalling strategies, psychological state, and physical impairment. This indicates that further research is needed to determine whether re-experiencing positive life events is adaptive or maladaptive.

Cancer hygiene hypothesis: A test from wild captive mammals.

The hygiene hypothesis, according to which the recent reduction of exposure to infectious agents in the human species would be the origin of various diseases, including autoimmune diseases and cancer, has often been proposed but not properly tested on animals. Here, we evaluated the relevance of this hypothesis to cancer risk in mammals in an original way, namely by using information on zoo mammals. We predicted that a higher richness of parasitic cohorts in the species' natural habitat would result in a greater occurrence of evolutionary mismatch due to the reduction of parasites in captive conditions. This, in turn, could contribute to an increased risk of developing lethal cancers. Using a comparative analysis of 112 mammalian species, we explored the potential relationship between cancer risk and parasite species richness using generalized phylogenetic least squares regressions to relate parasite species richness to cancer risk data. We found no strong evidence that parasite species richness increased cancer risk in zoo mammals for any of the parasite groups we tested. Without constituting definitive proof of the irrelevance of the hygienic hypothesis, our comparative study using zoo mammals does not support it, at least with respect to cancer risks.

Life history and cancer in birds: clutch size predicts cancer.

Cancer is a disease that affects nearly all multicellular life, including birds. However, little is known about what factors explain the variance in cancer prevalence among species. Litter size is positively correlated with cancer prevalence in managed species of mammals, and larger body size, but not incubation or nestling period, is linked to tumor prevalence in wild birds. Also, birds that produce more elaborate sexual traits are expected to have fewer resources for cancer defenses and thus higher cancer prevalence. In this study, we examined whether cancer prevalence is associated with a wide variety of life history traits (clutch size, incubation length, body mass, lifespan, and the extent of sexual dimorphism) across 108 species of managed birds in 25 different zoological facilities, sanctuaries, and veterinary clinics. We found that clutch size was positively correlated with cancer and neoplasia (both benign and malignant) prevalence, even after controlling for body mass. Cancer prevalence was not associated with incubation length, body mass, lifespan, or sexual dimorphism. The positive correlations of clutch size with cancer prevalence and neoplasia prevalence suggest that there may be life-history trade-offs between reproductive investment and somatic maintenance (in the form of cancer prevention mechanisms) in managed birds.

Cancer Prevalence Across Vertebrates.

Cancer is pervasive across multicellular species. Are there any patterns that can explain differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight and decreases with gestation time, contrary to Peto’s Paradox. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.

Cancer Prevalence Across Vertebrates.

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.

Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein.

The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein in Parkinson disease and multiple system atrophy, respectively; however, co-occurrence of α-synuclein with ß-amyloid (Aß) in human brain inclusions has been recently reported, suggesting the existence of mixed type pathologies that could result in obstacles in the correct diagnosis and treatment. Here we identified TPPP/p25 as an interacting partner of the soluble Aß oligomers as major risk factors for Alzheimer disease using ProtoArray human protein microarray. The interactions of oligomeric Aß with proteins involved in the etiology of neurological disorders were characterized by ELISA, surface plasmon resonance, pelleting experiments, and tubulin polymerization assay. We showed that the Aß(42) tightly bound to TPPP/p25 (K(d) = 85 nm) and caused aberrant protein aggregation by inhibiting the physiologically relevant TPPP/p25-derived microtubule assembly. The pair-wise interactions of Aß(42), α-synuclein, and tubulin were found to be relatively weak; however, these three components formed soluble ternary complex exclusively in the absence of TPPP/p25. The aggregation-facilitating activity of TPPP/p25 and its interaction with Aß was monitored by electron microscopy with purified proteins by pelleting experiments with cell-free extracts as well as by confocal microscopy with CHO cells expressing TPPP/p25 or amyloid. The finding that the interaction of TPPP/p25 with Aß can produce pathological-like aggregates is tightly coupled with unusual pathology of the Alzheimer disease revealed previously; that is, partial co-localization of Aß and TPPP/p25 in the case of diffuse Lewy body disease with Alzheimer disease.

[Wording and content of national anthems -- preliminary findings from a transcultural investigation of suicide]. / Nemzeti himnuszok szóhasználata és tartalomelemzése - elozetes eredmények egy transzkulturális szuicidium vizsgálatból.

Suicide is still a major health concern, although suicide rates widely differ among different countries and cultures. Thus, besides biological and clinical studies, there is an increasing transcultural research activity on suicidal behaviour. We are presenting here some important transcultural aspects of suicidal behaviour and report some preliminary findings of our transcultural suicide research. Based on the previous data and on our investigations it is likely that the national character and the attitudes toward self-harm are reflecting in some major cultural, historical texts of a nation.