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1.
PLoS Comput Biol ; 20(3): e1011888, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38446830

RESUMO

Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.


Assuntos
Fenômenos Genéticos , Neoplasias , Humanos , Avaliação Pré-Clínica de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/patologia
2.
Neuroimage ; 249: 118894, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35007717

RESUMO

Ample studies have reported a strong association between emotion and subcortical volumes; still, the underlying mechanism regarding this relation remains unclear. Using a twin design, the current study aimed to explore the intrinsic association between emotion and subcortical volumes by examining their phenotypic, genetic, and environmental correlations. We used a group dataset of 960 individuals from the Human Connectome Project (234 monozygotic twins, 145 dizygotic twins, 581 not twins, males = 454, age = 22-37 years). We found that both emotion and subcortical volumes were heritable. Of the 17 emotional traits, 13 were significantly phenotypically correlated with the volumes of multiple subcortical regions. There was no environmental correlation between emotion and subcortical volumes; however, we found a genetic overlap between overall emotional traits and caudate volume. Taken together, our results showed that emotion and subcortical volumes were heritable and closely related. Although the caudate has been often studied with execution of movement, given that the caudate volume is genetically associated with diverse emotional domains, such as negative affect, psychological well-being, and social relationships, it may suggest that the caudate volume might also be an important factor when studying the brain basis of emotion.


Assuntos
Núcleo Caudado/anatomia & histologia , Emoções/fisiologia , Fenômenos Genéticos/fisiologia , Satisfação Pessoal , Personalidade/genética , Interação Social , Adulto , Núcleo Caudado/diagnóstico por imagem , Feminino , Humanos , Masculino , Adulto Jovem
3.
Neuroimage ; 245: 118700, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34740793

RESUMO

Imaging genetics analyses use neuroimaging traits as intermediate phenotypes to infer the degree of genetic contribution to brain structure and function in health and/or illness. Coefficients of relatedness (CR) summarize the degree of genetic similarity among subjects and are used to estimate the heritability - the proportion of phenotypic variance explained by genetic factors. The CR can be inferred directly from genome-wide genotype data to explain the degree of shared variation in common genetic polymorphisms (SNP-heritability) among related or unrelated subjects. We developed a central processing and graphics processing unit (CPU and GPU) accelerated Fast and Powerful Heritability Inference (FPHI) approach that linearizes likelihood calculations to overcome the ∼N2-3 computational effort dependency on sample size of classical likelihood approaches. We calculated for 60 regional and 1.3 × 105 voxel-wise traits in N = 1,206 twin and sibling participants from the Human Connectome Project (HCP) (550 M/656 F, age = 28.8 ± 3.7 years) and N = 37,432 (17,531 M/19,901 F; age = 63.7 ± 7.5 years) participants from the UK Biobank (UKBB). The FPHI estimates were in excellent agreement with heritability values calculated using Genome-wide Complex Trait Analysis software (r = 0.96 and 0.98 in HCP and UKBB sample) while significantly reducing computational (102-4 times). The regional and voxel-wise traits heritability estimates for the HCP and UKBB were likewise in excellent agreement (r = 0.63-0.76, p < 10-10). In summary, the hardware-accelerated FPHI made it practical to calculate heritability values for voxel-wise neuroimaging traits, even in very large samples such as the UKBB. The patterns of additive genetic variance in neuroimaging traits measured in a large sample of related and unrelated individuals showed excellent agreement regardless of the estimation method. The code and instruction to execute these analyses are available at www.solar-eclipse-genetics.org.


Assuntos
Conectoma/métodos , Fenômenos Genéticos , Neuroimagem/métodos , Adulto , Algoritmos , Bancos de Espécimes Biológicos , Biologia Computacional , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único
5.
Chem Commun (Camb) ; 57(61): 7517-7520, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34235521

RESUMO

We demonstrate that a recombinase ribozyme achieves multiple functions in the same reaction network: self-reproduction, iterative elongation and circularization of other RNAs, leading to synthesis of diverse products predicted by a kinetic model. This shows that key mechanisms can be integrated and controlled toward Darwinian evolution in RNA reaction networks.


Assuntos
RNA Bacteriano/genética , RNA Catalítico/genética , RNA/genética , Azoarcus/enzimologia , Biocatálise , Fenômenos Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Sequências Repetidas Invertidas , Cinética , RNA/química , RNA Bacteriano/química , RNA Catalítico/química , Recombinases/química , Recombinases/genética
6.
Cancer Med ; 10(14): 4977-4993, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34076361

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD), as the most common subtype of lung cancer, is the leading cause of cancer deaths in the world. The accumulation of driver gene mutations enables cancer cells to gradually acquire growth advantage. Therefore, it is important to understand the functions and interactions of driver gene mutations in cancer progression. METHODS: We obtained gene mutation data and gene expression profile of 506 LUAD tumors from The Cancer Genome Atlas (TCGA). The subtypes of tumors with driver gene mutations were identified by consensus cluster analysis. RESULTS: We found 21 significantly mutually exclusive pairs consisting of 20 genes among 506 LUAD patients. Because of the increased transcriptomic heterogeneity of mutations, we identified subtypes among tumors with non-silent mutations in driver genes. There were 494 mutually exclusive pairs found among driver gene mutations within different subtypes. Furthermore, we identified functions of mutually exclusive pairs based on the hypothesis of functional redundancy of mutual exclusivity. These mutually exclusive pairs were significantly enriched in nuclear division and humoral immune response, which played crucial roles in cancer initiation and progression. We also found 79 mutually exclusive triples among subtypes of tumors with driver gene mutations, which were key roles in cell motility and cellular chemical homeostasis. In addition, two mutually exclusive triples and one mutually exclusive triple were associated with the overall survival and disease-specific survival of LUAD patients, respectively. CONCLUSIONS: We revealed novel mutual exclusivity and generated a comprehensive functional landscape of driver gene mutations, which could offer a new perspective to understand the mechanisms of cancer development and identify potential biomarkers for LUAD therapy.


Assuntos
Adenocarcinoma de Pulmão/genética , Progressão da Doença , Neoplasias Pulmonares/genética , Mutação/genética , Transcriptoma/genética , Adenocarcinoma de Pulmão/mortalidade , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Heterogeneidade Genética , Fenômenos Genéticos , Humanos , Neoplasias Pulmonares/mortalidade , Mutação/fisiologia
7.
Artif Life ; 26(3): 366-390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32772858

RESUMO

This article introduces GeMS, a system for music composition informed by synthetic biology. GeMS generates music with simulations of genetic processes, such as transcription, translation, and protein folding, with which biological systems render chains of amino acids from DNA strands. The system comprises the following components: the Miranda machine, the rhythmator, and the pitch processor. The Miranda machine is an abstract Turing-machine-like processor, which manipulates a sequence of DNA symbols according to a set of programming instructions. This process generates a pool of new DNA strands, which are subsequently translated into rhythms. GeMS represents the musical equivalent of amino acids in terms of rhythms, referred to as rhythmic codons. This enables the rhythmator to convert DNA sequences into rhythmic sequences. The pitch processor generates pitches for such rhythmic sequences. It is inspired by the phenomenon of protein folding. The pitch processor considers orientation information of DNA instructions yielded by the Miranda machine in order to activate algorithms for generating pitches. A musical composition, entitled Artibiotics, for percussion ensemble and electronic instruments, is presented to demonstrate the system.


Assuntos
DNA , Fenômenos Genéticos , Música , Biologia Sintética , Simulação por Computador , Biossíntese de Proteínas , Dobramento de Proteína , Transcrição Gênica
8.
Ned Tijdschr Geneeskd ; 1642020 06 04.
Artigo em Holandês | MEDLINE | ID: mdl-32613788

RESUMO

The central dogma in molecular biology states that genetic information is transmitted from DNA to RNA to proteins, but not the other way round. Thanks to a recent technological revolution - the 'RNAissance' - it has, however, become clear that RNA is not solely a messenger for passing on the genetic information necessary for protein synthesis, but that RNA also plays an important role in sickness and health. In the past 5 years alone more than 100 therapies with (complementary) RNA molecules have been investigated in Phase 1 trials, and a quarter of these have also been investigated in Phase 2 or 3 trials. The dramatic increase in the number of pharmaceutical companies that are developing RNA therapeutics illustrates the enormous potential of these medicines. Once the toxicity and the costs of RNA therapeutics can be limited, these medicines - personalized or not - could soon be prescribed for patients with a wide range of chronic conditions.


Assuntos
Doença Crônica/terapia , Terapia Genética/métodos , Medicina de Precisão , RNA , Fenômenos Genéticos , Humanos , Biologia Molecular/tendências
9.
Public Health Genomics ; 23(3-4): 149-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516789

RESUMO

Rising prices for new, transformative therapies are challenging health systems around the world, leading many payers and providers to begin rationing access to treatments, even in the countries that have been most resistant to doing so. This is the case for direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV). However, little attention has been paid to the increasing role that human genetics might play in rationing decisions. Researchers have already proposed that genetic markers associated with spontaneous HCV clearance could be used to restrict DAA access for some patients, although treatment would be medically beneficial for those patients. Would such forms of rationing present a form of genetic discrimination? And what of the public health implications of these approaches? Here we present an ethical analysis of such proposals for "precision rationing" and raise 4 key areas of concern. We argue that ethical issues arising in this area are not substantively different from the pressing ethical issues regarding rationing and discrimination more broadly, but provide important impetus for motivating broad public debate to find ethically sound ways of managing genomics and new expensive medications.


Assuntos
Fenômenos Genéticos , Hepatite C , Genética Humana , Seleção de Pacientes , Antivirais/economia , Antivirais/uso terapêutico , Testes Genéticos/métodos , Alocação de Recursos para a Atenção à Saúde/ética , Alocação de Recursos para a Atenção à Saúde/métodos , Acesso aos Serviços de Saúde , Hepatite C/tratamento farmacológico , Hepatite C/economia , Hepatite C/genética , Genética Humana/métodos , Genética Humana/tendências , Humanos
10.
Evol Comput ; 28(4): 677-708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357077

RESUMO

For the first time, a field programmable transistor array (FPTA) was used to evolve robot control circuits directly in analog hardware. Controllers were successfully incrementally evolved for a physical robot engaged in a series of visually guided behaviours, including finding a target in a complex environment where the goal was hidden from most locations. Circuits for recognising spoken commands were also evolved and these were used in conjunction with the controllers to enable voice control of the robot, triggering behavioural switching. Poor quality visual sensors were deliberately used to test the ability of evolved analog circuits to deal with noisy uncertain data in realtime. Visual features were coevolved with the controllers to automatically achieve dimensionality reduction and feature extraction and selection in an integrated way. An efficient new method was developed for simulating the robot in its visual environment. This allowed controllers to be evaluated in a simulation connected to the FPTA. The controllers then transferred seamlessly to the real world. The circuit replication issue was also addressed in experiments where circuits were evolved to be able to function correctly in multiple areas of the FPTA. A methodology was developed to analyse the evolved circuits which provided insights into their operation. Comparative experiments demonstrated the superior evolvability of the transistor array medium.


Assuntos
Robótica/instrumentação , Transistores Eletrônicos , Algoritmos , Inteligência Artificial/estatística & dados numéricos , Aprendizagem da Esquiva , Simulação por Computador , Desenho de Equipamento , Fenômenos Genéticos , Humanos , Redes Neurais de Computação , Robótica/estatística & dados numéricos , Interface para o Reconhecimento da Fala , Transistores Eletrônicos/estatística & dados numéricos
11.
Artigo em Inglês | MEDLINE | ID: mdl-32218770

RESUMO

Background: Height is considered an indicator of health and well-being of an individual and population. Height variation results from a complex interaction of genetic, environmental, socioeconomic, and cultural influences. In order to understand the contribution of environmental stress associated with the child's growth, we correlated indicators of a stressful environment with adult height. Methods: We utilized seven equally weighted indicators of a stressful environment: homicide rates, GDP per capita, income inequality (GINI index), corruption perception index (CPI), unemployment rate, urban air pollution, and life expectancy (LE). Data on male and female height by country from 1992 to 1996 were obtained from the NCD Risk Factor Collaboration dataset. We assessed separately data from the 31 member countries of the Organization for Economic Co-operation and Development (OECD). In order to establish whether the indicators reflected a single conceptual dimension, we conducted an exploratory analysis and principal component analysis (PCA) with orthogonal transformation of the original variables. The relationships between male and female heights and the z-transformed principal components: Quality of life (QoL) and the Social factor (SF) that were derived after the PCA was assessed. Results: Male and female heights strongly correlated (p < 0.0001) with each of the seven indicators. In the PCA, the indicators clustered into "Quality of Life" factors (QoL), which comprised the CPI, GDP, air pollution, LE, and "Social factors" (SF), which comprised homicide rate and GINI index. For males and females, the average height by country strongly correlated with QoL (p < 0.0001) and SF (p < 0.0001). Within OECD countries, male and female height strongly and negatively correlated with the SF, but not with QoL. Conclusion: Growth attenuation is a tradeoff adaptive response: a calorie used for growth cannot be used for fighting stress. Here we show that: (1) Adult height, when used as a measure of child's growth, is an indicator of a stressful environment in context with the genetic background and spatial factors; (2) Stressful QoL factors and the SF exert a greater effect on men's height than women's height; and (3) The ranking of the indicators of short stature are income inequality > air pollution > GDP > CPI > homicide rate > LE > unemployment.


Assuntos
Estatura , Desenvolvimento Infantil/fisiologia , Meio Ambiente , Adulto , Estatura/genética , Estatura/fisiologia , Criança , Países em Desenvolvimento/estatística & dados numéricos , Feminino , Fenômenos Genéticos/fisiologia , Geografia , Homicídio/psicologia , Homicídio/estatística & dados numéricos , Humanos , Renda/estatística & dados numéricos , Expectativa de Vida , Masculino , Qualidade de Vida , Meio Social , Fatores Socioeconômicos , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Populações Vulneráveis
12.
Evol Comput ; 28(4): 643-675, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101028

RESUMO

We present a study demonstrating how random walk algorithms can be used for evolutionary image transition. We design different mutation operators based on uniform and biased random walks and study how their combination with a baseline mutation operator can lead to interesting image transition processes in terms of visual effects and artistic features. Using feature-based analysis we investigate the evolutionary image transition behaviour with respect to different features and evaluate the images constructed during the image transition process. Afterwards, we investigate how modifications of our biased random walk approaches can be used for evolutionary image painting. We introduce an evolutionary image painting approach whose underlying biased random walk can be controlled by a parameter influencing the bias of the random walk and thereby creating different artistic painting effects.


Assuntos
Algoritmos , Arte , Viés , Fenômenos Genéticos , Humanos , Processamento de Imagem Assistida por Computador , Pinturas , Distribuição Aleatória
13.
PLoS Comput Biol ; 16(1): e1007643, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004314

RESUMO

For a genetically identical microbial population, multi-gene expression in various environments requires effective allocation of limited resources and precise control of heterogeneity among individual cells. However, it is unclear how resource allocation and cell-to-cell variation jointly shape the overall performance. Here we demonstrate a Simpson's paradox during overexpression of multiple genes: two competing proteins in single cells correlated positively for every induction condition, but the overall correlation was negative. Yet this phenomenon was not observed between two competing mRNAs in single cells. Our analytical framework shows that the phenomenon arises from competition for translational resource, with the correlation modulated by both mRNA and ribosome variability. Thus, heterogeneity plays a key role in single-cell multi-gene expression and provides the population with an evolutionary advantage, as demonstrated in this study.


Assuntos
Regulação Bacteriana da Expressão Gênica/genética , Expressão Gênica/genética , Genes Bacterianos/genética , Biologia Computacional , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fenômenos Genéticos/genética , Modelos Estatísticos , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Neurosci Biobehav Rev ; 109: 78-89, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31899301

RESUMO

Twin studies have shown that a substantial proportion of the variance for sleep variables is due to genetic factors. However, there is still considerable heterogeneity among research reports. Our main objectives were to: 1) Review the twin literature regarding sleep quality and duration, as well as their behavioural correlates; 2) Estimate the mean heritability of subjective sleep quality and sleep duration; 3) Assess heterogeneity among studies on these topics; and 4) Search for moderator variables. Two parallel meta-analyses were carried out for sleep quality and sleep duration. Seventeen articles were included in the meta-analysis. Mean MZ correlations were consistently higher than DZ correlations. A mean heritability of 0.31 (95% CI: 0.20, 0.41) was found for subjective sleep quality (range: 0-0.43) and 0.38 (95% CI: 0.16, 0.56) for sleep duration (range: 0-1). Heterogeneity indexes were significant for both sleep quality (I2 = 98.77, p < .001) and sleep duration (I2 = 99.73, p < .001). The high heterogeneity warrants further research considering possible moderators that may affect heritability.


Assuntos
Fenômenos Genéticos/fisiologia , Sono/fisiologia , Estudos em Gêmeos como Assunto/estatística & dados numéricos , Humanos
15.
Child Obes ; 16(1): 59-64, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31596604

RESUMO

Background/Objective: Understanding the influence of genetically determined ancestry may give insight into the disparities of obesity seen in different ethnic groups beginning at a very early age. Aim: To investigate the relationship between children's ancestral genetic proportions and excess weight at 12 months of age. Methods: Eight hundred twenty-one 12-month-old children were included in this cross-sectional study. Their genetic admixture was estimated using the ancestry and kinship tool kit by projecting the samples into the 1000 Genomes principal component database. Weight-for-length percentile (WFLP) at 12 months of age was categorized as <95th percentile or ≥95th percentile. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association of admixture proportions, including European (EUR), admixed American (AMR), African (AFR), South Asian (SAS), and East Asian (EAS) populations, with WFLP categories, adjusting for maternal education, birth weight, frequency of breastfeeding, and juice consumption. Results: Eight hundred twenty-one children were included; WFLP <95th percentile = 671 (81.7%) and WFLP ≥95th percentile = 150 (18.3%). Crude ORs showed that the EUR admixture was protective [OR 0.45 (95% CI 0.27-0.74)], whereas AMR [OR 3.85 (95% CI 1.92-7.70)] and AFR [OR 5.70 (95% CI 2.19-14.85)] admixtures were positively associated with excess weight. After adjusting for confounding variables, only the AFR admixture was associated with WFLP ≥95th percentile [OR 7.38 (95% CI 2.31-23.59)]. Conclusions: AFRs remain associated with early excess weight after accounting for confounding variables, suggesting that this ancestral genetic background may contribute to the differences seen in early childhood obesity.


Assuntos
Peso Corporal/genética , Obesidade Pediátrica/genética , Grupos Raciais/genética , Estatura/genética , Estudos Transversais , Feminino , Fenômenos Genéticos/genética , Genoma Humano/genética , Humanos , Lactente , Masculino , Fatores de Risco
16.
Evol Comput ; 28(4): 531-561, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31599651

RESUMO

Clustering is a difficult and widely studied data mining task, with many varieties of clustering algorithms proposed in the literature. Nearly all algorithms use a similarity measure such as a distance metric (e.g., Euclidean distance) to decide which instances to assign to the same cluster. These similarity measures are generally predefined and cannot be easily tailored to the properties of a particular dataset, which leads to limitations in the quality and the interpretability of the clusters produced. In this article, we propose a new approach to automatically evolving similarity functions for a given clustering algorithm by using genetic programming. We introduce a new genetic programming-based method which automatically selects a small subset of features (feature selection) and then combines them using a variety of functions (feature construction) to produce dynamic and flexible similarity functions that are specifically designed for a given dataset. We demonstrate how the evolved similarity functions can be used to perform clustering using a graph-based representation. The results of a variety of experiments across a range of large, high-dimensional datasets show that the proposed approach can achieve higher and more consistent performance than the benchmark methods. We further extend the proposed approach to automatically produce multiple complementary similarity functions by using a multi-tree approach, which gives further performance improvements. We also analyse the interpretability and structure of the automatically evolved similarity functions to provide insight into how and why they are superior to standard distance metrics.


Assuntos
Algoritmos , Análise por Conglomerados , Mineração de Dados/métodos , Simulação por Computador , Mineração de Dados/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Fenômenos Genéticos , Modelos Estatísticos , Software
17.
Drug Discov Today ; 25(2): 438-445, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31562982

RESUMO

Large-scale biobanks can yield unprecedented insights into our health and provide discoveries of new and potentially targetable biomarkers. Several protective loss-of-function alleles have been identified, including variants that protect against cardiovascular disease, obesity, type 2 diabetes, and asthma and allergic diseases. These alleles serve as indicators of efficacy, mimicking the effects of drugs and suggesting that inhibiting these genes could provide therapeutic benefit, as has been observed for PCSK9. We provide a context for these findings through a multifaceted review covering the use of genetics in drug discovery efforts through genome-wide and phenome-wide association studies, linking deep mutation scanning data to molecular function and highlighting some additional tools that might help in the interpretation of newly discovered variants.


Assuntos
Bancos de Espécimes Biológicos , Descoberta de Drogas , Fenômenos Genéticos , Animais , Desenvolvimento de Medicamentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
18.
J Psychosom Obstet Gynaecol ; 41(1): 62-68, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31023109

RESUMO

Introduction: A lot of attention has been given to the quest of parents, children and donors to find donor siblings (= half siblings who share the same donor gametes but who are born in different families). However, literature is scarce about the use of the same sperm donor for subsequent children in the same family.Methods: This study included 68 lesbian and heterosexual (aspiring) parents, recruited at the Department of Reproductive Medicine of Ghent University Hospital (Belgium). The in-depth semi-structured couple interviews were performed between October 2012 and October 2013. Data were analyzed through step-by-step inductive thematic analysis.Results: The couples showed a clear preference to use the same sperm donor for their children. The most common reasons for this preference were related to the family or sibling relationships and medical reasons. Uncertainty about the availability of the same donor over time seeped through in their stories. Most lesbian aspiring parents decided that both partners should have a genetic link with at least one child.Conclusion: The use of the same sperm donor for subsequent conceptions appeared quasi unambiguously in the interviews of the lesbian and heterosexual (aspiring) parents in our study.


Assuntos
Fenômenos Genéticos , Poder Familiar/psicologia , Pais/psicologia , Técnicas de Reprodução Assistida/psicologia , Relações entre Irmãos , Irmãos , Doadores de Tecidos , Adulto , Feminino , Heterossexualidade , Humanos , Masculino , Relações Pais-Filho , Pesquisa Qualitativa , Minorias Sexuais e de Gênero , Doadores de Tecidos/psicologia , Doadores de Tecidos/estatística & dados numéricos
19.
Econ Hum Biol ; 36: 100826, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865267

RESUMO

Whether individuals perceive their income as being fair has far-reaching consequences in the labor market and beyond. Yet we know little about the determinants of variation in perceived income justice across individuals. In this paper, we ask to what extent differences in genes are related to variation in individuals' perceived income justice, and whether there is a gene-environment component. Analyzing data from the German TwinLife study, we find that more than 30% of individuals' perceived income justice can be attributed to genes. The rest is mostly related to an idiosyncratic environment.


Assuntos
Interação Gene-Ambiente , Fenômenos Genéticos , Renda/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Fatores Socioeconômicos
20.
Cell ; 179(5): 1129-1143.e23, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31730854

RESUMO

Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.


Assuntos
Comportamento Alimentar/fisiologia , Fenômenos Genéticos , Células Receptoras Sensoriais/fisiologia , Nervo Vago/fisiologia , Proteína Relacionada com Agouti/metabolismo , Animais , Encéfalo/fisiologia , Trato Gastrointestinal/inervação , Marcadores Genéticos , Mecanorreceptores/metabolismo , Camundongos , Nervo Vago/anatomia & histologia , Vísceras/inervação
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