Genetic architecture of craniofacial shape in the house mouse: a genetic and morphological perspective

Morphological diversity in nature is astounding. A remarkable example of such diversity is the vertebrate cranium. This structure is developmentally, anatomically, and functionally integrated with the many other tissues and sensory systems of the head. Because of this, it is under strong constrains to achieve an adult form (size and shape) compatible with the functional requirements of the individual. The genetic basis of craniofacial diversity has been traditionally studied from a macro-evolutionary perspective (i.e. at the between-species level), with special focus on adaptive radiation and domestication. The work presented in this thesis is an attempt to understand the genetic basis of craniofacial shape variation in the house mouse. By using between-subspecies and within population variation, I address the question from a micro-evolutionary perspective. In this thesis I also explore the genetic architecture of the traits (i.e. number, effect size, and genomic distribution of the causal loci), and the extent to which phenotypic variation can be explained by genetic variation – i.e. heritability of the traits. The first two chapters of this thesis are the first genome-wide approximation to the genetic architecture of craniofacial shape and size in mice. I combine highly recombinant mouse populations –wild hybrid mice and outbred lab mice- with dense marker coverage of the genome to map the loci underlying phenotypic variation. I identify genes previously known to be involved in craniofacial formation, and provide a list of genomic regions that contain new candidate genes for craniofacial development. Regarding the genetic architecture, I show that craniofacial traits are highly polygenic and highly heritable, with many loci of very small effect distributed uniformly along the genome. The last chapter of the thesis is an assessment of the morphological transition associated with the degree of admixture between two subspecies of the house mouse, Mus musculus musculus and Mus musculus domesticus. I show that craniofacial shape changes, but not size changes, are correlated with the level of admixture. The transition from M. m. musculus to M. m. domesticus is continuous, such mode would be expected from a trait with polygenic architecture, and therefore these results are in line with the genetic results obtained in previous chapters. Overall the work presented in this thesis is the first genome-wide analyses of the genetic basis and genetic architecture of craniofacial shape variation in the house mouse. It is also the first time shape variation is explored in a close-to-natural context; previous work used crosses between inbred 10 mouse strains. Therefore, the results reported here are directly relevant to the understanding of complex traits evolution

Fractoluminescence characterization of the energy dissipated during fast fracture of glass

Fractoluminescence experiments are performed on two kinds of silicate glasses. All the light spectra collected during dynamic fracture reveal a black body radiator behaviour, which is interpreted as a crack velocity-dependent temperature rise close to the crack tip. Crack velocities are estimated to be of the order of 1300 m.s$^{-1}$ and fracture process zones are shown to extend over a few nanometers.Comment: Accepted for publication in Europhysics Letters; 5 pages; 4 figure

The New (Old) Genetics, Version 1.0

The field of Genetics started flourishing after the rediscovery of the Mendelian laws of inheritance at the beginning of the 20th century. These laws are based on a discrete classification of phenotypes and their causative genes. Such a Mendelian way of thinking forms the foundation of modern molecular biology, with its experimental paradigm that a gene function is inferred from the knock-out of the gene. However, most phenotypes are not discrete. Human height, for example, is a continuous phenotype and height measures approximate a Gaussian distribution. The statistical foundation for the genetics of human height was worked out by GALTON at the end of the 19th century. He established the basis of quantitative genetics, a field that has driven the agricultural and breeding programs in the past century. It is not until very recently that the technical developments behind the human genome project have paved the way to reconcile the two contrasting ways of genetic thinking – Mendelian genetics and statistical genetics – through genome-wide analyses. It has now become clear that most phenotypes are rarely determined by single Mendelian genes, but instead, many genes contribute to their determination and variation. It has even been suggested in the omnigenic model that all genes that are expressed at the appropriate time contribute to any given phenotype. These insights are stimulating a major rethinking of how the linear genetic information laid down in the deoxyribonucleic acid (DNA) is converted into the threedimensional structure of an individual. The new conceptual and experimental paradigms have already revolutionized animal and plant breeding. In the field of human genetics, the realization that common diseases also have a polygenic basis is raising new challenges for treatment. And finally, in basic sciences like molecular and evolutionary biology, researchers are starting to revisit traditional, but oversimplified concepts on how genes act and how evolutionary adaptation works

Use of a natural hybrid zone for genome-wide association mapping of craniofacial traits in the house mouse

The identification of the genes involved in morphological variation in nature is still a major challenge. Here we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~145K SNPs) to identify loci underlying craniofacial shape variation. Due to the long history of recombination in the hybrid zone, high mapping resolution is anticipated. The combination of genomes from subspecies allows the mapping of both, variation within subspecies and intersubspecific differences, thereby increasing the overall amount of causal genetic variation than can be detected. Skull and mandible shape were measured using 3D landmarks and geometric morphometrics. Using principle component axes as phenotypes, and a linear mixed model accounting for genetic relatedness in the mapping populations, we identified 9 genomic regions associated with skull and 10 with mandible shape. High mapping resolution (median size of significant regions = 148 kb) enabled identification of single or few candidate genes in most cases. Some of the genes act as regulators or modifiers of signaling pathways relevant for morphological development and bone formation, including several with known craniofacial phenotypes in mice and humans. The significant associations combined explain 13% and 7% of the skull and mandible shape variation. In addition, a positive correlation was found between chromosomal length and proportion of variation explained. Our results suggest a complex genetic architecture for shape traits, and support a polygenic model

Human biomonitoring of t-2 toxin, t-2 toxin-3-glucoside and their metabolites in urine through high-resolution mass spectrometry

The metabolic profile of T-2 toxin (T-2) and its modified form T-2-3-glucoside (T-2-3-Glc) remain unexplored in human samples. Therefore, the present study aimed to investigate the presence of T-2, T-2-3-Glc and their respective major metabolites in human urine samples (n = 300) collected in South Italy through an ultra-high performance liquid chromatography (UHPLC) coupled to Q-Orbitrap-HRMS methodology. T-2 was quantified in 21% of samples at a mean concentration of 1.34 ng/mg Crea (range: 0.22–6.54 ng/mg Crea). Almost all the major T-2 metabolites previously characterized in vitro were tentatively found, remarking the occurrence of 3′-OH-T-2 (99.7%), T-2 triol (56%) and HT-2 (30%). Regarding T-2-3-Glc, a low prevalence of the parent mycotoxin (1%) and its metabolites were observed, with HT-2-3-Glc (17%) being the most prevalent compound, although hydroxylated products were also detected. Attending to the large number of testing positive for T-2 or its metabolites, this study found a frequent exposure in Italian population

Patrones de aprendizaje, rasgos de personalidad y perfil motivacional de los estudiantes de la modalidad de aprendizaje dual

The aim of this research article is to identify the profile of students enrolled in dual learning model and standard learning model based on personality traits, learning patterns and motivational orientation. Participants included 212 freshmen enrolled dual learning model (N=97) and standard model (N=115) in the Primary Education Degree. The participants completed 3 questionnaires: (1) Learning Combination In-ventory (Johnston & Dainton, 1996), (2) Big-Five Personality Inventory (Bermúdez, 1995), and (3) Motivational Profile Inventory (Corral, Arribas & Fernández, 2010). The results showed that the students who enrolled in dual learning modality tend to be less open, more emotionally stable and take care of their relationships to a greater extent. The two later characteristics are essential for the typology of the learning modality because it is more complex to work and learn in two different environ-ments than one as standard learning. Despite these results, the groups of both learning modalities are similar and therefore possible future lines are considered. Future studies should be conducted with much larger samples and longitudinal de-sign that allows corroborating (or not) that the students who study in dual learning modality are different or can vary their motivational orientations or improve their learning patterns during the course of their training.El objetivo de este estudio es identificar cual es el perfil de los estudiantes que se matriculan en una modalidad de aprendizaje dual o tradicional teniendo en cuenta los rasgos de personalidad, patrones de aprendizaje y orientaciones motivacionales. Participaron 212 estudiantes de primer año matriculados en la modalidad de aprendizaje dual (N=97) y tradicional (N=115) del grado de Educación Primaria. Los participantes completaron 3 cuestionarios: (1) Learning Combination Inventory (Johnston & Dainton, 1996), (2) Big-Five Personality Inventory (Bermúdez, 1995) y (3) Motivational Profile Inventory (Corral, Arribas & Fernández, 2010). Los resultados mostraron que los estudiantes matriculados en la modalidad de aprendizaje dual tienden a ser menos abiertos, más estables emocionalmente y cuidan sus relaciones. Estas dos últimas características son esenciales para la tipología de modalidad de aprendizaje, ya que requiere más complejidad para trabajar y aprender en dos entornos a diferencia de un único entorno como el aprendizaje tradicional. A pesar de estos resultados, los grupos de ambas modalidades de aprendizaje son similares y por consiguiente se plantean posibles líneas de futuro. Estudios futuros deberían ampliar la muestra incluyendo diseños de tipo longitudinal que permitan corroborar (o no) que los estudiantes que estudian en modalidad de aprendizaje dual pueden son diferentes o pueden variar sus orientaciones motivacionales o mejorar sus patrones de aprendizaje durante el transcurso de su formación

ENOBIO - First tests of a dry electrophysiology electrode using carbon nanotubes

We describe the development and first tests of Enobio, a dry electrode sensor concept for biopotential applications. In the proposed electrodes, the tip of the electrode is covered with a forest of multi-walled CNTs that can be coated with Ag/AgCl to provide ionic-electronic transduction. The CNT brush-like structure is to penetrate the outer layers of the skin improving electrical contact as well as increae the contact surface area. In this paper, we report the results of the first tests of this concept -- immersion on saline solution and pig skin signal detection. These indicate performance on a par with state of the art research-oriented wet electrodes.Comment: Submitted and accepted at the 28th IEEE EMBS International Conference, New York City, August 31st-September 3rd, 2006. Figures updated with proper filtering and averagin

Fluorescence sensing of protein-DNA interactions using conjugated polyelectrolytes and graphene oxide

© 2018 Protein-DNA binding, particularly transcription factor-DNA binding, is one of the main molecular interactions involved in gene regulation. These interactions are sequence-specific, play a key role in many fundamental biological processes, and are deregulated in the pathogenesis of several diseases. In this study, a robust analytical bioassay to characterize protein-DNA binding was built by combining the optical properties of water soluble conjugated polyelectrolytes, and graphene oxide's superquenching capabilities. Cationic conjugated polyelectrolytes bind strongly to double stranded DNA through electrostatic interactions, and provide fluorescent signals to track the DNA without any chemical modification. In addition, the labeled DNA retains its protein binding ability. An important oncogenic transcription factor (i.e. estrogen receptor α) was used to demonstrate the concept, and two collaborative factors involved in the estrogen gene transcription (i.e. forkhead box A1 and activating enhancer binding protein 2 gamma) were employed as controls. This method overcame the main limitations of previous nanomaterial-based bioassays, while keeping the sensitivity and precision of the gold standard techniques. These benefits, combined with the high versatility and low-costs, could lead this bioassay to be used in several fundamental biomedical research lines, such as large scale protein-DNA binding studies and drug discovery

An evaluation of management strategies for Atlantic tuna stocks

International agreements for the International Commission for the Conservation of Atlantic Tunas (ICCAT) convention area imply that Atlantic tuna stocks should be managed by strategies based on maximum sustainable yield (MSY); however, there is concern whether this will actually ensure sustainability with sufficiently high probability consistent with the principals of the precautionary approach. Therefore, the performance of MSY management strategies based on current assessment procedures was evaluated using a computer simulation framework. The framework includes the data collection, assessment, prediction, and management processes, as well as the implementation of management regulations. It therefore provides an integrated way to evaluate the relative importance of and the interactions between each component of the system with regard to the overall success of the management strategy. The study elucidates guidelines about assessment and management that are general enough to be applied to all tunas in the Atlantic Ocean. It does so by comparing different hypotheses about management and assessment for three stocks (North Atlantic albacore, Atlantic bigeye and East Atlantic skipjack), which are representative of the variety encountered (i.e. from data rich to poor and tropical to temperate waters) in ICCAT stocks. Management performance was especially sensitive to the carrying capacity of the stock. The type of proxy used for MSY was more important to the success of the procedure than the frequency of assessment or the number of indices used in the assessment. Whilst the procedure was successful at achieving the management objectives for albacore, it was only partially successful for bigeye and was too conservative for skipjack.No disponibl