In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.

Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV uptake can lead to transfer of functional mRNA and altered cellular behavior. However, similar in vivo experiments remain challenging because cells that take up EVs cannot be discriminated from non-EV-receiving cells. Here, we used the Cre-LoxP system to directly identify tumor cells that take up EVs in vivo. We show that EVs released by malignant tumor cells are taken up by less malignant tumor cells located within the same and within distant tumors and that these EVs carry mRNAs involved in migration and metastasis. By intravital imaging, we show that the less malignant tumor cells that take up EVs display enhanced migratory behavior and metastatic capacity. We postulate that tumor cells locally and systemically share molecules carried by EVs in vivo and that this affects cellular behavior.

Testing Fraternal Birth Order Effects and Antagonistic Effects for Homosexual Men: Power Comparison of Various Methods.

Research on the biological determinants of male homosexual preference has long realized that the older brother effect (FBOE, i.e., a higher fraternal birth rank of homosexuals) and the antagonist effect (AE, i.e., more fertile women have a higher chance of having a homosexual son) can both generate family data where homosexual men have more siblings and more older siblings than heterosexual men. Various statistical approaches were proposed in the recent literature to evaluate whether the action of FBOE or AE could be discriminated from empirical data, by controlling for the other effect. Here, we used simulated data to formally compare all the approaches that we could find in the relevant literature for their ability to reject the null hypothesis in the presence of a specified alternative hypothesis (tests based on regression, Bayesian modeling, or contingency tables). When testing for the FBOE, the relative performance of the different tests was different depending on the specific function generating the older brother effect. Even if no tests were found to always perform better than the others, some tests performed systematically poorly, and some tests displayed a systematic high rate of type-I error. For testing the AE, the relative performance of the tests was generally not changed across all parameter values assayed, providing a clear ranking of the various proposed approaches. Pros and cons for each candidate test are discussed, taking into consideration power and the rate of type-I error but also practicability, the possibility to control for confounding variables, and to consider alternative hypotheses.

Sexual Recidivism During Treatment: Impact on Therapists.

There are few studies of therapists' reactions to working with individuals who have committed sexual offenses, and almost none on reactions following sexual recidivism by a patient who is currently in treatment. Consequently, the aim of the current study was to analyze the cognitive and emotional reactions, as well as the intervention strategies, of therapists who have learned of the sexual recidivism of a patient. A total of 59 participants from the province of Quebec (Canada) completed a questionnaire on their reactions to this event. Participants' responses to their patient's recidivism varied as a function of gender, experience, and the way they learned of the recidivism. The most common cognitions reported were thinking of the victim and thinking about the consequences of further judicialization for the patient and those close to them. The most common emotions reported were sadness for the victim and fear that the patient would reoffend again. The most common intervention strategies were being sensitive to the experience of the patient and asking the patient what drove them to offend. Support measures for therapists working with individuals who have committed sexual offenses during treatment are discussed.

Can postfertile life stages evolve as an anticancer mechanism?

Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses. During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies. At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers. Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.

Handedness heritability in industrialized and nonindustrialized societies.

In modern societies, there is a decreased usage of traditional weapons to settle interpersonal or inter-group disputes compared to usage in traditional societies, possibly affecting the frequency-dependent selection on the handedness polymorphism. Another societal difference is the extensive automation of hard manual labour (including agriculture) in industrialized societies, relaxing the selection for hand specialization. Thus, selection of handedness is likely to differ between traditional and modern societies. As heritability determines the relative speed of evolutionary dynamics, handedness heritability was compared between industrialized and non-industrialized societies. First, individuals were sampled from a non-industrialized area in Indonesia, where violent conflicts are relatively frequent and tribal wars have been prevalent recently. Handedness was recorded directly or indirectly for 11,490 individuals belonging to 650 independent pedigrees, and handedness heritability was estimated using a pedigree-based animal model. Second, estimates of handedness heritability derived from published sources were collected to compare heritability estimates, accounting for various confounding variables. Non-industrialized countries displayed a significantly higher heritability value (h2 = 0.56) than that of industrialized countries (h2 = 0.20). Heritability decreased with time along the twentieth century in industrialized countries, independently of the frequency of left-handedness, and independently of the method used to measure handedness. In conclusion, the data are consistent with a decrease in handedness heritability following the industrialization process and/or the associated decrease in violence using traditional weapons. The difference in heritability between industrialized and non-industrialized countries suggests that selection of handedness is thus likely to differ between traditional and modern societies.

Speech Acoustic Features: A Comparison of Gay Men, Heterosexual Men, and Heterosexual Women.

Potential differences between homosexual and heterosexual men have been studied on a diverse set of social and biological traits. Regarding acoustic features of speech, researchers have hypothesized a feminization of such characteristics in homosexual men, but previous investigations have so far produced mixed results. Moreover, most studies have been conducted with English-speaking populations, which calls for further cross-linguistic examinations. Lastly, no studies investigated so far the potential role of testosterone in the association between sexual orientation and speech acoustic features. To fill these gaps, we explored potential differences in acoustic features of speech between homosexual and heterosexual native French men and investigated whether the former showed a trend toward feminization by comparing theirs to that of heterosexual native French women. Lastly, we examined whether testosterone levels mediated the association between speech acoustic features and sexual orientation. We studied four sexually dimorphic acoustic features relevant for the qualification of feminine versus masculine voices: the fundamental frequency, its modulation, and two understudied acoustic features of speech, the harmonics-to-noise ratio (a proxy of vocal breathiness) and the jitter (a proxy of vocal roughness). Results showed that homosexual men displayed significantly higher pitch modulation patterns and less breathy voices compared to heterosexual men, with values shifted toward those of heterosexual women. Lastly, testosterone levels did not influence any of the investigated acoustic features. Combined with the literature conducted in other languages, our findings bring new support for the feminization hypothesis and suggest that the feminization of some acoustic features could be shared across languages.

Probability of myopia in children with high refined carbohydrates consumption in France.

BACKGROUND: Evaluate risk factors for paediatric myopia in a contemporary French cohort taking into account consumption of refined carbohydrates (starches and sugars). METHODS: An epidemiological cross-sectional study was conducted between May 2017 and May 2018. Two hundred sixty-four children aged 4 to 18 years attending the Centre Hospitalier Universitaire Gui de Chauliac in Montpellier were recruited. Ophthalmologic or optometric cycloplegic refraction were measured. Evaluated risk factors for myopia were collected, including family history of myopia, outdoor time, reading time, screen time, physical activity, and consumption of refined carbohydrates. Association between the probability of at least one eye showing myopia (defined as < 0 D) and frequency of refined carbohydrates consumption adjusted for risk factors and control factors was tested. RESULTS: Overall, 86/264 (32.6%) children investigated showed myopia in at least one eye. We included 180 children exhibiting refraction < 3 D in both eyes: 88 (48.9%) girls and 92 (51.1%) boys. The consumption of refined carbohydrates significantly increased the probability of myopia for girls (odds ratio [OR] = 1.07; 95% confidence interval [CI], 1.02-1.13; P = 0.009) but decreased it for boys (OR = 0.94; 95% CI, 0.89-0.98; P = 0.011). The probability of myopia was marginally increased with increased screen time (OR = 2.32; 95% CI, 0.94-6.47; P = 0.083). Outdoor time seemed marginally protective (OR = 0.74; 95% CI, 0.54-1.01; P = 0.057). CONCLUSION: Refined carbohydrates consumption could be associated with child myopia, with increased probability for girls and unexpected reduced probability for boys, possibly due to the fact that frequency of carbohydrates consumption do not really capture boy's chronic hyperglycemia, boys being more physically active than girls at all ages. Some known risk/protective factors of myopia were marginally significant: screen time (risk) and outdoor time (protective). This study reinforces the belief that modifiable risk factors for myopia could be targets for future public health actions.

Refined carbohydrate-rich diet is associated with long-term risk of dementia and Alzheimer's disease in apolipoprotein E ε4 allele carriers.

INTRODUCTION: In animal models, refined carbohydrates (RF) worsen Alzheimer's disease (AD). However, the long-term effects of high RF intake on the risk of dementia and AD are poorly described in epidemiological studies. Moreover, the interaction between RF and the apolipoprotein E ε4 allele (APOE-ε4) is unknown. Our study investigated whether RF-rich diets are associated with the risk of dementia and AD. METHODS: The glycemic load (GL) was quantified in 2777 elderly participants from the French Three-City Study to estimate RF intake. Then, the associations between GL and risk of dementia and AD, and the interaction with APOE-ε4 over a 12-year period were assessed using proportional hazards models. RESULTS: After adjustment for potential confounders, high afternoon-snack GL was associated with increased dementia and AD risk in APOE-ε4 carriers (hazard ratio = 1.27 [1.03-1.56]). DISCUSSION: This study highlights that RF-rich diets are a risk factor for dementia and AD in APOE-ε4 carriers.

3D Bioprinting: from Benches to Translational Applications.

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high-resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.

Experimental evidence for the influence of group size on cultural complexity.

The remarkable ecological and demographic success of humanity is largely attributed to our capacity for cumulative culture. The accumulation of beneficial cultural innovations across generations is puzzling because transmission events are generally imperfect, although there is large variance in fidelity. Events of perfect cultural transmission and innovations should be more frequent in a large population. As a consequence, a large population size may be a prerequisite for the evolution of cultural complexity, although anthropological studies have produced mixed results and empirical evidence is lacking. Here we use a dual-task computer game to show that cultural evolution strongly depends on population size, as players in larger groups maintained higher cultural complexity. We found that when group size increases, cultural knowledge is less deteriorated, improvements to existing cultural traits are more frequent, and cultural trait diversity is maintained more often. Our results demonstrate how changes in group size can generate both adaptive cultural evolution and maladaptive losses of culturally acquired skills. As humans live in habitats for which they are ill-suited without specific cultural adaptations, it suggests that, in our evolutionary past, group-size reduction may have exposed human societies to significant risks, including societal collapse.

Grandmothering and cognitive resources are required for the emergence of menopause and extensive post-reproductive lifespan.

Menopause, the permanent cessation of ovulation, occurs in humans well before the end of the expected lifespan, leading to an extensive post-reproductive period which remains a puzzle for evolutionary biologists. All human populations display this particularity; thus, it is difficult to empirically evaluate the conditions for its emergence. In this study, we used artificial neural networks to model the emergence and evolution of allocation decisions related to reproduction in simulated populations. When allocation decisions were allowed to freely evolve, both menopause and extensive post-reproductive life-span emerged under some ecological conditions. This result allowed us to test various hypotheses about the required conditions for the emergence of menopause and extensive post-reproductive life-span. Our findings did not support the Maternal Hypothesis (menopause has evolved to avoid the risk of dying in childbirth, which is higher in older women). In contrast, results supported a shared prediction from the Grandmother Hypothesis and the Embodied Capital Model. Indeed, we found that extensive post-reproductive lifespan allows resource reallocation to increase fertility of the children and survival of the grandchildren. Furthermore, neural capital development and the skill intensiveness of the foraging niche, rather than strength, played a major role in shaping the age profile of somatic and cognitive senescence in our simulated populations. This result supports the Embodied Capital Model rather than the Grand-Mother Hypothesis. Finally, in simulated populations where menopause had already evolved, we found that reduced post-reproductive lifespan lead to reduced children's fertility and grandchildren's survival. The results are discussed in the context of the evolutionary emergence of menopause and extensive post-reproductive life-span.

Kin Selection and Male Homosexual Preference in Indonesia.

Male homosexual preference (MHP) challenges evolutionary thinking because the preference for male-male relationships is heritable, implies a fertility cost (lower offspring number), and is relatively frequent in some societies (2-6% in Western countries) for a costly trait. It has been proposed that individuals with a MHP counterbalance reproductive costs through the transfer of resources to kin, thereby improving their indirect reproduction through kin's reproductive success. This kin selection hypothesis is not supported in Western countries and Japan, although consistent evidence has been obtained in Samoa. In this study, data from Java (Indonesia) were obtained to assess the avuncular tendencies of men with contrasting sexual orientation to measure possible resource transfer. Consistent with the kin selection hypothesis, males with a homosexual orientation reported an increased willingness to transfer resources toward nephews and nieces and declared having transferred more money to nephews and nieces. We developed a method to quantitatively estimate the contribution of kin selection on inclusive reproduction associated to sexual orientation, taking into account various possible biases. Kin selection reduced the direct reproductive cost of homosexual men by 20%, so suggesting that kin selection alone is insufficient to explain the maintenance of male homosexuality. Other potential factors are discussed, as well as the limitations of the study and the social determinant operating for the expression of increased avuncular tendencies of homosexual men.

Emergence and maintenance of menopause in humans: A game theory model.

Menopause, the permanent cessation of ovulation, occurs in women well before the end of their expected life span. Several adaptive hypotheses have been proposed to solve this evolutionary puzzle, each based on a possible fitness benefit derived from an early reproductive senescence, but no consensus has emerged. The construction of a game theory model allowed us to jointly study the main adaptive hypotheses in emergence and maintenance of menopause. Four classical hypotheses on the benefits of menopause were considered (decreased maternal mortality, increased grandmothering, decreased conflict over reproductive resources between older and younger females, and changes in their relatedness) plus a fifth one derived from a possible pleiotropic trade-off. Interestingly, the conditions for the emergence of menopause are more restrictive than those for its maintenance due to the social and familial changes induced by the occurrence of non-reproductive older women.

Social learning and the replication process: an experimental investigation.

Human cultural traits typically result from a gradual process that has been described as analogous to biological evolution. This observation has led pioneering scholars to draw inspiration from population genetics to develop a rigorous and successful theoretical framework of cultural evolution. Social learning, the mechanism allowing information to be transmitted between individuals, has thus been described as a simple replication mechanism. Although useful, the extent to which this idealization appropriately describes the actual social learning events has not been carefully assessed. Here, we used a specifically developed computer task to evaluate (i) the extent to which social learning leads to the replication of an observed behaviour and (ii) the consequences it has for fitness landscape exploration. Our results show that social learning does not lead to a dichotomous choice between disregarding and replicating social information. Rather, it appeared that individuals combine and transform information coming from multiple sources to produce new solutions. As a consequence, landscape exploration was promoted by the use of social information. These results invite us to rethink the way social learning is commonly modelled and could question the validity of predictions coming from models considering this process as replicative.

Identification of visual paternity cues in humans.

Understanding how individuals identify their relatives has implications for the evolution of social behaviour. Kinship cues might be based on familiarity, but in the face of paternity uncertainty and costly paternal investment, other mechanisms such as phenotypic matching may have evolved. In humans, paternal recognition of offspring and subsequent discriminative paternal investment have been linked to father-offspring facial phenotypic similarities. However, the extent to which paternity detection is impaired by environmentally induced facial information is unclear. We used 27 portraits of fathers and their adult sons to quantify the level of paternity detection according to experimental treatments that manipulate the location, type and quantity of visible facial information. We found that (i) the lower part of the face, that changes most with development, does not contain paternity cues, (ii) paternity can be detected even if relational information within the face is disrupted and (iii) the signal depends on the presence of specific information rather than their number. Taken together, the results support the view that environmental effects have little influence on the detection of paternity using facial similarities. This suggests that the cognitive dispositions enabling the facial detection of kinship relationships ignore genetic irrelevant facial information.

Chronic and immediate refined carbohydrate consumption and facial attractiveness.

The Western diet has undergone a massive switch since the second half of the 20th century, with the massive increase of the consumption of refined carbohydrate associated with many adverse health effects. The physiological mechanisms linked to this consumption, such as hyperglycaemia and hyperinsulinemia, may impact non medical traits such as facial attractiveness. To explore this issue, the relationship between facial attractiveness and immediate and chronic refined carbohydrate consumption estimated by glycemic load was studied for 104 French subjects. Facial attractiveness was assessed by opposite sex raters using pictures taken two hours after a controlled breakfast. Chronic consumption was assessed considering three high glycemic risk meals: breakfast, afternoon snacking and between-meal snacking. Immediate consumption of a high glycemic breakfast decreased facial attractiveness for men and women while controlling for several control variables, including energy intake. Chronic refined carbohydrate consumption had different effects on attractiveness depending on the meal and/or the sex. Chronic refined carbohydrate consumption, estimated by the glycemic load, during the three studied meals reduced attractiveness, while a high energy intake increased it. Nevertheless, the effect was reversed for men concerning the afternoon snack, for which a high energy intake reduced attractiveness and a high glycemic load increased it. These effects were maintained when potential confounders for facial attractiveness were controlled such as age, age departure from actual age, masculinity/femininity (perceived and measured), BMI, physical activity, parental home ownership, smoking, couple status, hormonal contraceptive use (for women), and facial hairiness (for men). Results were possibly mediated by an increase in age appearance for women and a decrease in perceived masculinity for men. The physiological differences between the three meals studied and the interpretation of the results from an adaptive/maladaptive point of view in relation to our new dietary environment are discussed.

Associations between screen viewing at 2 and 3.5 years and drawing ability at 3.5 years among children from the French nationwide Elfe birth cohort.

The effect of screen viewing on children's cognitive development has been of concern among parents and researchers. This study investigated the association between children screen time, as reported by parents, and drawing ability, and the confounding effects of socioeconomic characteristics (such as parental education, household income, migration status) and children's competing activities (such as drawing practice, extracurricular activity, outdoor time, sleep time, time playing with parents). Participants included 7577 children aged 3.5 years (50% girls) who underwent the Draw-a-person test (McCarthy score [range = 0-12 points]) in the French nationwide Elfe birth cohort, initiated in 2011. Sex-stratified zero-inflated Poisson regression models were used. Increased screen time was associated with a higher likelihood to obtain a null score in boys (OR 1.15, 95% CI 1.07-1.23) and girls (1.13 [1.03-1.24]) and a lower score in girls only (ß = - 0.02, 95% CI - 0.04; - 0.01). After adjusting for SES, associations were no longer observed, indicating that the association between screen time and drawing abilities was confounded by socioeconomic characteristics.

Recommended distances for physical distancing during COVID-19 pandemics reveal cultural connections between countries.

During COVID-19 pandemic several public health measures were implemented by diverse countries to reduce the risk of COVID-19, including social distancing. Here we collected the minimal distance recommended by each country for physical distancing at the onset of the pandemic and aimed to examine whether it had an impact on the outbreak dynamics and how this specific value was chosen. Despite an absence of data on SARS-CoV-2 viral transmission at the beginning of the pandemic, we found that most countries recommended physical distancing with a precise minimal distance, between one meter/three feet and two meters/six feet. 45% of the countries advised one meter/three feet and 49% advised a higher minimal distance. The recommended minimal distance did not show a clear correlation with reproduction rate nor with the number of new cases per million, suggesting that the overall COVID-19 dynamics in each country depended on multiple interacting factors. Interestingly, the recommended minimal distance correlated with several cultural parameters: it was higher in countries with larger interpersonal distance between two interacting individuals in non-epidemic conditions, and it correlated with civil law systems, and with currency. This suggests that countries which share common conceptions such as civil law systems and currency unions tend to adopt the same public health measures.