"Nem tão doentes, nem tão livres de doença": narrativas de mulheres com câncer de mama sobre a investigação da herança genética em um instituto oncológico de pesquisa / "Ni tan enfermas, ni tan libres de la enfermidad": relatos de mujeres con cáncer de mama sobre la investigación de la herencia genética en un instituto de investigación oncológica / "Not so sick, not so disease-free": narratives of women with breast cancer about the investigation of genetic inheritance in an oncological research institute

A tese versa sobre a susceptibilidade hereditária para o câncer de mama sob um olhar socioantropológico. O tema apresenta relevância em função da atual valorização da genética na área da oncologia e dos impactos que esse campo da medicina produz na vida das pessoas e famílias envolvidas. A partir de uma produção etnográfica, buscou-se compreender como a prática do aconselhamento genético interfere em diversos planos da vida de mulheres com câncer de mama hereditário, como o psicoafetivo, social e familiar, atendidas por um instituto oncológico de pesquisa, pertencente ao setor privado de saúde. Para investigação metodológica, utilizou-se um conjunto de dados empíricos: entrevistas semiestruturadas com mulheres com (suspeita de) câncer de mama hereditário, observação de consultas com o serviço de genética e documentos online relativos à hereditariedade da doença na mama. Como resultados, constatou-se de que modos às percepções biomédicas acerca da noção de risco atravessaram a produção de subjetividades, identidades e coletividades das interlocutoras. Outros pontos explorados nas narrativas foram: as repercussões, individuais e coletivas, ocasionadas pela experiência do aconselhamento genético e o entrelaçamento da doença e da hereditariedade a outras vivências de cunho individual. O estudo visou contribuir a dar visibilidade às experiências e as demandas das mulheres investigadas e somar aos estudos risco, biotecnologias e subjetividades.AU

This thesis is about hereditary susceptibility to breast cancer from a socio-anthropological perspective. The theme is relevant due to the current appreciation of the genetics field in the oncological area and the impact on the lives of people and families involved. From an ethnographical starting point, how genetic counselling interferes with the life planning of women with hereditary breast cancer breast in areas such as psycho-affective, social and familiar. The search was conducted in an oncological research institute that belongs to the private healthcare system. For the methodological research, it was used a set of empirical data: semi-structured interviews with (suspected) hereditary breast cancer; participant observation of genetic consultations and online documents related to the heredity of the disease in the breast. As result, it has been noticed how the biomedical perceptions about the notion of risk cross through to the interlocutors' subjective productions, identities and sense of collective. Another aspect of the narratives is the relationship of genetics with oncological illness. It also stands out the individual and collective repercussions caused by the experience of genetic counselling and the intertwining of the disease and heredity with other individual experiences. The study aimed to contribute to giving visibility to the experiences and demands of the women investigated and also to add studies of the risk, biotechnologies and subjectivities.AU

La tesis aborda la susceptibilidad hereditaria al cáncer de mama desde una perspectiva socio-antropológica. El tema es relevante debido a la actual valorización de la genética en el área de la oncología y a los impactos que ese campo de la medicina tiene en la vida de las personas y familias. Con base en una producción etnográfica, buscamos comprender cómo la práctica del asesoramiento genético interfiere en diferentes áreas de la vida de mujeres con cáncer de mama hereditario, como el psicoafectivo, social y familiar, asistidas por un instituto de investigación oncológica, perteneciente al sector privado del cuidado de la salud. La investigación se fundamenta en un conjunto de datos empíricos: entrevistas semiestructuradas con mujeres con (sospecha de) cáncer de mama hereditario, observación de consultas en el servicio de genética y documentos en línea relacionados con la herencia familiar de la enfermedad. Como resultado, se constató como las percepciones sobre la biomedicina sobre la noción de riesgo atraviesan la producción de subjetividades, identidades y colectividades de las interlocutoras. Otros puntos explorados en las narrativas fueron: las repercusiones individuales y colectivas provocadas por la experiencia de la consejería genética y el entrelazamiento de la enfermedad y la herencia con otras experiencias de carácter individual. El estudio pretendió dar visibilidad a las experiencias y demandas de las mujeres investigadas y contribuir a los estudios sobre riesgo, biotecnologías y subjetividades. AU

Heritable consequences of paternal nicotine exposure: from phenomena to mechanisms†.

Our understanding of the interactions between genetic and environmental factors in shaping behavioral phenotypes has expanded to include environment-induced epigenetic modifications and the intriguing possibility of their association with heritable behavioral phenotypes. The molecular basis of heritability of phenotypes arising from environment-induced epigenetic modifications is not well defined yet. However, phenomenological evidence in favor of it is accumulating rapidly. The resurgence of interest has led to focus on epigenetic modification of germ cells as a plausible mechanism of heritability. Perhaps partly because of practical reasons such as ease of access to male germ cells compared to female germ cells, attention has turned toward heritable effects of environmental influences on male founders. Public health implications of heritable effects of paternal exposures to addictive substances or to psycho-social factors may be enormous. Considering nicotine alone, over a billion people worldwide use nicotine-containing products, and the majority are men. Historically, the adverse effects of nicotine use by pregnant women received much attention by scientists and public policy experts alike. The implications of nicotine use by men for the physical and mental well-being of their children were not at the forefront of research until recently. Here, we review progress in the emerging field of heritable effects of paternal nicotine exposure and its implications for behavioral health of individuals in multiple generations.

Ancient genomes provide insights into family structure and the heredity of social status in the early Bronze Age of southeastern Europe.

Twenty-four palaeogenomes from Mokrin, a major Early Bronze Age necropolis in southeastern Europe, were sequenced to analyse kinship between individuals and to better understand prehistoric social organization. 15 investigated individuals were involved in genetic relationships of varying degrees. The Mokrin sample resembles a genetically unstructured population, suggesting that the community's social hierarchies were not accompanied by strict marriage barriers. We find evidence for female exogamy but no indications for strict patrilocality. Individual status differences at Mokrin, as indicated by grave goods, support the inference that females could inherit status, but could not transmit status to all their sons. We further show that sons had the possibility to acquire status during their lifetimes, but not necessarily to inherit it. Taken together, these findings suggest that Southeastern Europe in the Early Bronze Age had a significantly different family and social structure than Late Neolithic and Early Bronze Age societies of Central Europe.

[Concern about liver disease in children].

With the economic development and living standards improvement, various chronic viral liver diseases in children is decreasing year by year, and the liver diseases related to heredity, environment and living habits is increasing. Although liver disease in children is relatively rare and is not the main cause of childhood mortality, chronic liver disease cannot be ignored for its effect on children's growth and development, mental health, quality of life and the economic burden to family or society. Therefore, more attention should be paid to the early screening, diagnosis and treatment of pediatric liver diseases, in order to delay or prevent its progression efficiently.

Different perspectives on non-genetic inheritance illustrate the versatile utility of the Price equation in evolutionary biology.

The diversity of genetic and non-genetic processes that make offspring resemble their parents are increasingly well understood. In addition to genetic inheritance, parent-offspring similarity is affected by epigenetic, behavioural and cultural mechanisms that collectively can be referred to as non-genetic inheritance. Given the generality of the Price equation as a description of evolutionary change, is it not surprising that the Price equation has been adopted to model the evolutionary implications of non-genetic inheritance. In this paper, we briefly introduce the heredity perspectives on which those models rely, discuss the extent to which these perspectives make different assumptions and place different emphases on the roles of heredity and development in evolution, and the types of empirical research programmes they motivate. The existence of multiple perspectives and explanatory aims highlight, on the one hand, the versatility of the Price equation and, on the other hand, the importance of understanding how heredity and development can be conceptualized in evolutionary studies. This article is part of the theme issue 'Fifty years of the Price equation'.

Are Moral Intuitions Heritable?

Two prominent theoretical frameworks in moral psychology, Moral Foundations and Dual Process Theory, share a broad foundational assumption that individual differences in human morality are dispositional and in part due to genetic variation. The only published direct test of heritability, however, found little evidence of genetic influences on moral judgments using instrumentation approaches associated with Moral Foundations Theory. This raised questions about one of the core assumptions underpinning intuitionist theories of moral psychology. Here we examine the heritability of moral psychology using the moral dilemmas approach commonly used in Dual Process Theory research. Using such measures, we find consistent and significant evidence of heritability. These findings have important implications not only for understanding which measures do, or do not, tap into the genetically influenced aspects of moral decision-making, but in better establishing the utility and validity of different intuitionist theoretical frameworks and the source of why people differ in those frameworks.

Inheritance and fitness costs of resistance to Bacillus thuringiensis toxin Cry2Ad in laboratory strains of the diamondback moth, Plutella xylostella (L.).

The diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae), is one of the main pests of Brassica crops worldwide. Management of P. xylostella is particularly challenging, as different field populations have readily acquired resistance to a wide range of insecticides, including Bacillus thuringiensis (Bt) toxins. In this study, a novel strain of P. xyllostela (Fuzhou-R2Ad) with 120-fold resistance to Bt Cry2Ad was selected in the laboratory, after screening for 66 generations from the susceptible strain Fuzhou-S. In the absence of Bt Cry2Ad toxin, the Fuzhou-R2Ad had significantly lower fitness as compared to the susceptible strain, which might be related to induced genetic changes to Bt toxins. We used several models to measure the dominance levels of insecticide resistance among different strains and found an incompletely recessive inheritance pattern of the Fuzhou-R2Ad resistance, which might be controlled by multiple genes. This study constitutes the first report of laboratory-acquired resistance to Cry2Ad toxin in P. xylostella. Our work presents further insights into the mechanism of Bt resistance and has immediate implications for the integrated pest management of P. xylostella globally.

Inheritance and fitness costs of sulfoxaflor resistance in Nilaparvata lugens (Stål).

BACKGROUND: Sulfoxaflor has been considered as a new tool for Nilaparvata lugens control in the field. In this study, a laboratory-selected resistant strain and a susceptible strain were used to evaluate the inheritance and fitness costs of sulfoxaflor resistance in N. lugens. RESULTS: The resistant strain (SFX-SEL) showed 123.63-fold resistance compared with the susceptible strain (SS). Progenies of reciprocal crosses (F1 RS and F1 SR) showed similar concentration-mortality responses (LC50 ) to sulfoxaflor and also exhibited a similar degree of dominance; -0.16 for F1 RS and -0.26 for F1 SR. Significant differences between the observed and expected mortalities of F2 individuals suggested that sulfoxaflor resistance is associated with multiple genes. The resistant strain had a relative fitness of 0.75 with substantially decreased female adult period, oviposition days, total fecundity, egg hatchability and female adult survival rate, and prolonged pre-adult period and total pre-oviposition period. CONCLUSION: Sulfoxaflor resistance in N. lugens was inherited as autosomal, incompletely recessive and multigene. The development of resistance may have a significant fitness cost for the resistant population. Current research provides valuable information for researchers to establish management strategies to delay the development of sulfoxaflor resistance and control N. lugens sustainably in the field. © 2019 Society of Chemical Industry.

School tracking and its role in social reproduction: reinforcing educational inheritance and the direct effects of social origin.

The degree of social reproduction varies considerably between industrialized countries, raising the question of which institutional regulations promote or restrict this process. Education is considered the main mediator of social reproduction. Because school tracking - the sorting of children according to ability and interest at different ages - is known to affect educational attainment and the degree of tracking varies strongly across countries, it may thus account for differences in social reproduction. However, empirical studies are scarce, and the total impact of tracking on social reproduction remains ambiguous. Using the European Social Survey (ESS) 2012 and 2014 from 24 countries, we demonstrate that school tracking is strongly associated with higher degrees of social reproduction. Decomposing the process of social reproduction into educational inheritance, educational returns and direct effects of social origin, we find that although all channels contribute to social reproduction, the impact of tracking seems to be exerted through educational inheritance and to a similar degree through direct effects of social origin, whereas educational returns do not seem to be affected. Even net of educational attainment, social origin thus has a stronger effect on social status in tracked systems. We ascribe this effect to differences in qualitative choices within educational tracks, such as fields of study.

Identification of novel mutations and risk assessment of Han Chinese patients with autosomal dominant polycystic kidney disease.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in humans and is caused by mutations in the PKD1 or PKD2 gene. ADPKD is heterogeneous with regard to locus and allele heterogeneity and phenotypic variability. METHODS: Using targeted capture associated with next generation sequencing (NGS), we performed a mutational analysis of Han Chinese patients with ADPKD from 62 unrelated families. Multivariate Cox proportional hazard modelling of their different clinical characteristics and mutation classes was performed. RESULTS: The detection rate for a PKD1 and PKD2 mutation in the Chinese ADPKD patients was 95.2% (59/62). We identified pathogenic mutations in 64.4% (38/59) of patients, including 32PKD1 mutations (15 nonsense mutations, 15 frameshift mutation, one splice mutation, and one large deletion) and six PKD2 mutations (three nonsense mutations and three frameshift mutations). Of the pathogenic variants we identified, 50% (19/38) were novel variants and 50% (19/38) were known variants. Patients with PKD2 mutations had milder and indistinguishable phenotypes. Significant phenotypic differences were observed among the various types of PKD1 mutations. CONCLUSION: Our results show that targeted capture associated with next-generation sequencing is an effective strategy for genetically testing ADPKD patients. This mutation analysis of ADPKD in Han Chinese extends our understanding of the genetic diversity of different ethnic groups, enriches the mutation database, and contributes to the genetic counselling of ADPKD patients.

Human progress by human effort: neo-Darwinism, social heredity, and the professionalization of the American social sciences, 1889-1925.

Prior to August Weismann's 1889 germ-plasm theory, social reformers believed that humans could inherit the effects of a salubrious environment and, by passing environmentally-induced modifications to their offspring, achieve continuous progress. Weismann's theory disrupted this logic and caused many to fear that they had little control over human development. As numerous historians have observed, this contributed to the birth of the eugenics movement. However, through an examination of the work of social scientists Lester Frank Ward, Richard T. Ely, Amos Griswold Warner, James Mark Baldwin, Simon Nelson Patten, Alfred Kroeber, Walter Robinson Smith, and Luther Lee Bernard, I demonstrate that Weismann's ideas also prompted scholars to create of theories of human progress in which the social environment had a central role and biological heredity had a diminished one. Furthermore, in creating a new theory of social progress based on a concept called "social heredity," the thinkers surveyed in this article separated biological and social thought and asserted the independence of the American social sciences. I argue that this represents an important moment in the maturation of the human sciences, and I suggest that the germ-plasm theory of heredity deserves a larger place in histories of the development of the American social scientific disciplines.

Genetic structure of pharmacogenetic biomarkers in Brazil inferred from a systematic review and population-based cohorts: a RIBEF/EPIGEN-Brazil initiative.

We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity issues, being social constructs pervasively used in Brazilian society and medical studies; (2) are associated with disparities in access to health services, as well as in their representation in genetic studies, and (3), as we report here, explain a larger portion of the variance of pharmaco-allele frequencies than geography. We integrated a systematic review of studies on healthy volunteers (years 1968-2017) and the analysis of allele frequencies on three population-based cohorts from northeast, southeast, and south, the most populated regions of Brazil. Cross-validation of results from these both approaches suggest that, despite methodological heterogeneity of the 120 studies conducted on 51,747 healthy volunteers, allele frequencies estimates from systematic review are reliable. We report differences in allele frequencies between color categories that persist despite the homogenizing effect of >500 years of admixture. Among clinically relevant variants: CYP2C9*2 (null), CYP3A5*3 (defective), SLCO1B1-rs4149056(C), and VKORC1-rs9923231(A) are more frequent in Whites than in Blacks. Brazilian Native Americans show lower frequencies of CYP2C9*2, CYP2C19*17 (increased activity), and higher of SLCO1B1-rs4149056(C) than other Brazilian populations. We present the most current and informative database of pharmaco-allele frequencies in Brazilian healthy volunteers.

Resistance selection of indoxacarb in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae): cross-resistance, biochemical mechanisms and associated fitness costs.

BACKGROUND: The cotton bollworm Helicoverpa armigera is a worldwide insect pest with the ability to develop resistance to many insecticides. Indoxacarb, a sodium channel blocker, is an important insecticide that is used to control H. armigera. Cross-resistance, metabolic mechanisms and life history traits were established for an indoxacarb-selected (IND-SEL) population of H. armigera. RESULTS: After 11 generations of selection, the susceptibility to indoxacarb was decreased by 4.43-fold and the estimated realized heritability (h2 ) was only 0.072. Interestingly, the IND-SEL population was more susceptible to methoxyfenozide and abamectin than the susceptible population. The activities of cytochrome P450 monooxygenase (P450) and carboxyl esterase (CarE) were significantly increased in IND-SEL H. armigera. Thus, susceptibility to indoxacarb was increased by piperonyl butoxide and S,S,S-tributyl phosphorothioate, showing synergistic ratios of 2.54- and 1.82-fold, respectively. Moreover, the IND-SEL population had a reduced relative fitness (0.67), with a lower growth rate and fecundity than the susceptible population. CONCLUSIONS: Evidence from this study suggests that decreased susceptibility to indoxacarb may be associated with fitness costs in H. armigera and enhanced activities of P450 and CarE may be important detoxification mechanisms in the development of indoxacarb resistance. Methoxyfenozide and abamectin can be rotationally used to manage indoxacarb resistance. © 2018 Society of Chemical Industry.

Sex Differences in Ischemic Heart Disease: Advances, Obstacles, and Next Steps.

Evolving knowledge of sex-specific presentations, improved recognition of conventional and novel risk factors, and expanded understanding of the sex-specific pathophysiology of ischemic heart disease have resulted in improved clinical outcomes in women. Yet, ischemic heart disease continues to be the leading cause of morbidity and mortality in women in the United States. The important publication by the Institute of Medicine titled "Women's Health Research-Progress, Pitfalls, and Promise," highlights the persistent disparities in cardiovascular disease burden among subgroups of women, particularly women who are socially disadvantaged because of race, ethnicity, income level, and educational attainment. These important health disparities reflect underrepresentation of women in research, with the resultant unfavorable impact on diagnosis, prevention, and treatment strategies in women at risk for cardiovascular disease. Causes of disparities are multifactorial and related to differences in risk factor prevalence, access to care, use of evidence-based guidelines, and social and environmental factors. Lack of awareness in both the public and medical community, as well as existing knowledge gap regarding sex-specific differences in presentation, risk factors, pathophysiology, and response to treatment for ischemic heart disease, further contribute to outcome disparities. There is a critical need for implementation of sex- and gender-specific strategies to improve cardiovascular outcomes. This review is tailored to meet the needs of a busy clinician and summarizes the contemporary trends, characterizes current sex-specific outcome disparities, delineates challenges, and proposes transformative solutions for improvement of the full spectrum of ischemic heart disease clinical care and research in women.

Estimating impacts of the nuclear family and heritability of nutritional outcomes in a boat-dwelling community.

OBJECTIVES: General health status is reflected in measures of height, weight, and BMI. Assessing sources of variation in these outcomes reveals population-specific variables of importance to health and nutrition. We characterize the impacts of socioeconomic variables related to the nuclear family on health outcomes of boat-dwelling Shodagor children, mothers, and fathers, and to estimate the proportion of variation in height, weight, and BMI influenced by both genetic variation and nongenetic variation among household environments. METHODS: Bayesian linear mixed models (LMMs) estimate heritability and household-effect variance components among the Shodagor. These models also assess the influences of specific socioeconomic predictor variables on different types of individuals within the household (children, mothers, and fathers). RESULTS: Overall, models explain 61.7% of variation in height, 59.4% in weight, and 65.8% in BMI for this sample of Shodagor. Mother's decision-making and household income have expected, positive associations with children's weight and BMI. Number of children has an unexpected positive relationship to children's height and a negative relationship to father's BMI. Genetic variation explains less than 26% of phenotypic variation for each of these traits on average. CONCLUSIONS: Our results show that resource flows and distributions within Shodagor households account for a significant amount of variance in nutritional outcomes. Problems commonly associated with increasing market integration may lead to negative outcomes for children, while mother's autonomy may lead to positive outcomes. Our models also indicate that environmental factors account for more variation in these outcomes than expected, relative to genetics, and we discuss the implications.