903 resultados para Human genome - Theses


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Previous research has characterized human mate poaching as a prevalent alternative mating strategy that entails risks and costs typically not present during general romantic courtship and attraction. This study is the first to experimentally investigate friendship between a poacher and poachee as a risk mitigation tactic. Participants (N = 382) read a vignette that differed by whether the poacher was male/female and whether the poacher and poachee were friends/acquaintances. Participants assessed the likelihood of the poacher being successful and incurring costs. They also rated the poacher and poachee on several personality and mate characteristics. Results revealed that friendship increased the perceived likelihood of success of a mate poaching attempt and decreased the perceived likelihood of several risks typically associated with mate poaching. However, friend-poachers were rated less favorably than acquaintance-poachers across measures of warmth, nurturance, and friendliness. These findings are interpreted using an evolutionary perspective. This study complements and builds upon previous findings and is the first experimental investigation of tactics mate poachers may use to mitigate risks inherent in mate poaching.

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Most primates live in highly complex social systems, and therefore have evolved similarly complex methods of communicating with each other. One type of communication is the use of manual gestures, which are only found in primates. No substantial evidence exists indicating that monkeys use communicative gestures in the wild. However, monkeys may demonstrate the ability to learn and/or use gestures in certain experimental paradigms since they¿ve been shown to use other visual cues such as gaze. The purpose of this study was to investigate if ten brown capuchin monkeys (Cebus apella) were able to use gestural cues from monkeys and a pointing cue from a human to obtain a hidden reward. They were then tested to determine if they could transfer this skill from monkeys to humans and from humans to monkeys. One group of monkeys was trained and tested using a conspecific as the cue giver, and was then tested with a human cue-giver. The second group of monkeys began training and testing with a human cue giver, and was then tested with a monkey cue giver. I found that two monkeys were able to use gestural cues from conspecifics (e.g., reaching) to obtain a hidden reward and then transfer this ability to a pointing cue from a human. Four monkeys learned to use the human pointing cue first, and then transferred this ability to use the gestural cues from conspecifics to obtain a hidden reward. However, the number of trials it took for each monkey to transfer the ability varied considerably. Some subjects spontaneously transferred in the minimum number of trials needed to reach my criteria for successfully obtaining hidden rewards (N = 40 trials), while others needed a large number of trials to do so (e.g. N = 190 trials). Two subjects did not perform successfully in any of the conditions in which they were tested. One subject successfully used the human pointing cue and a human pointing plus vocalization cue, but did not learn the conspecific cue. One subject learned to use the conspecific cue but not the human pointing cue. This was the first study to test if brown capuchin monkeys could use gestural cues from conspecifics to solve an object choice task. The study was also the first to test if capuchins could transfer this skill from monkeys to humans and from humans to monkeys. Results showed that capuchin monkeys were able to flexibly use communicative gestures when they were both unintentionally given by a conspecific and intentionally given by a human to indicate a source of food.

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The primary objective of this thesis is to demonstrate the pernicious impact that moral hierarchies have on our perception and subsequent treatment of non-human animals. Moral hierarchies in general are characterized by a dynamic in which one group is considered to be fundamentally superior to a lesser group. This thesis focuses specifically on the moral hierarchies that arise when humans are assumed to be superior to non-human animals in virtue of their advanced mental capabilities. The operative hypothesis of this thesis is essentially that moral hierarchies thwart the provision of justice to non-human animals in that they function as a justification for otherwise impermissible actions. When humans are assumed to be fundamentally superior to non-human animals then it becomes morally permissible for humans to kill non-human animals and utilize them as mere instrumentalities. This thesis is driven primarily by an in-depth analysis of the approaches to animal rights that are provided by Peter Singer, Tom Regan, and Gary Francione. Each of these thinkers claim that they overcome anthropocentrism and provide approaches that preclude the establishment of a moral hierarchy. One of the major findings of this thesis, however, is that Singer and Regan offer approaches that remain highly anthropocentric despite the fact that each thinker claims that they have overcome anthropocentrism. The anthropocentrism persists in these respective approaches in that each thinkers gives humans Regan and Singer have different conceptions of the criteria that are required to afford a being moral worth, but they both give preference to beings that have the cognitive ability to form desires regarding the future.. As a result, a moral hierarchy emerges in which humans are regarded to be fundamentally superior. Francione, however, provides an approach that does not foster a moral hierarchy. Francione creates such an approach by applying the principle of equal consideration of interests in a consistent manner. Moreover, Francione argues that mere sentience is both a necessary and sufficient condition for being eligible and subsequently receiving moral consideration. The upshot of this thesis is essentially that the moral treatment of animals is not compatible with the presence of a moral hierarchy. As a result, this thesis demonstrates that future approaches to animal rights must avoid the establishment of moral hierarchies. The research and analysis within this thesis demonstrates that this is not a possibility, however, unless all theories of justice that are to accommodate animals abandon the notion that cognition matters morally.

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Advances in novel molecular biological diagnostic methods are changing the way of diagnosis and study of metabolic disorders like growth hormone deficiency. Faster sequencing and genotyping methods require strong bioinformatics tools to make sense of the vast amount of data generated by modern laboratories. Advances in genome sequencing and computational power to analyze the whole genome sequences will guide the diagnostics of future. In this chapter, an overview of some basic bioinformatics resources that are needed to study metabolic disorders are reviewed and some examples of bioinformatics analysis of human growth hormone gene, protein and structure are provided.

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In this study, 231 strains of Yersinia enterocolitica, 25 strains of Y. intermedia, and 10 strains of Y. bercovieri from human and porcine sources (including reference strains) were analyzed using amplified fragment length polymorphism (AFLP), a whole-genome fingerprinting method for subtyping bacterial isolates. AFLP typing distinguished the different Yersinia species examined. Representatives of Y. enterocolitica biotypes 1A, 1B, 2, 3, and 4 belonged to biotype-related AFLP clusters and were clearly distinguished from each other. Y. enterocolitica biotypes 2, 3, and 4 appeared to be more closely related to each other (83% similarity) than to biotypes 1A (11%) and 1B (47%). Biotype 1A strains exhibited the greatest genetic heterogeneity of the biotypes studied. The biotype 1A genotypes were distributed among four major clusters, each containing strains from both human and porcine sources, confirming the zoonotic potential of this organism. The AFLP technique is a valuable genotypic method for identification and typing of Y. enterocolitica and other Yersinia spp.

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PURPOSE: Integration of high-risk papillomavirus DNA has been considered an important step in oncogenic progression to cervical carcinoma. Disruption of the human papillomavirus (HPV) genome within the E2 gene is frequently a consequence. This study investigated the influence of episomal viral DNA on outcome in patients with advanced cervical cancer treated with primary radiotherapy. METHODS AND MATERIALS: Paraffin-embedded biopsies of 82 women with locally advanced cervical cancer could be analyzed for HPV infection by multiplex polymerase chain reaction (PCR) by use of SPF1/2 primers. E2-gene intactness of HPV-16-positive samples was analyzed in 3 separate amplification reactions by use of the E2A, E2B, E2C primers. Statistical analyses (Kaplan-Meier method; log-rank test) were performed for overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS), and distant metastases-free survival (DMFS). RESULTS: Sixty-one (75%) of 82 carcinomas were HPV positive, 44 of them for HPV-16 (72%). Seventeen of the 44 HPV-16-positive tumors (39%) had an intact E2 gene. Patients with a HPV-16-positive tumor and an intact E2 gene showed a trend for a better DFS (58% vs. 38%, p = 0.06) compared with those with a disrupted E2 gene. A nonsignificant difference occurred regarding OS (87% vs. 66%, p = 0.16) and DMFS (57% vs. 48%, p = 0.15). CONCLUSION: E2-gene status may be a promising new target, but more studies are required to elucidate the effect of the viral E2 gene on outcome after radiotherapy in HPV-positive tumors.

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PURPOSE: To characterize the phenotype and map the locus responsible for autosomal recessive inherited ovine microphthalmia (OMO) in sheep. METHODS: Microphthalmia-affected lambs and their available relatives were collected in a field, and experimental matings were performed to obtain affected and normal lambs for detailed necropsy and histologic examinations. The matings resulted in 18 sheep families with 48 cases of microphthalmia. A comparative candidate gene approach was used to map the disease locus within the sheep genome. Initially, 27 loci responsible for the microphthalmia-anophthalmia phenotypes in humans or mice were selected to test for comparative linkage. Fifty flanking markers that were predicted from comparative genomic analysis to be closely linked to these genes were tested for linkage to the disease locus. After observation of statistical evidence for linkage, a confirmatory fine mapping strategy was applied by further genotyping of 43 microsatellites. RESULTS: The clinical and pathologic examinations showed slightly variable expressivity of isolated bilateral microphthalmia. The anterior eye chamber was small or absent, and a white mass admixed with cystic spaces extended from the papilla to the anterior eye chamber, while no recognizable vitreous body or lens was found within the affected eyes. Significant linkage to a single candidate region was identified at sheep chromosome 23. Fine mapping and haplotype analysis assigned the candidate region to a critical interval of 12.4 cM. This ovine chromosome segment encompasses an ancestral chromosomal breakpoint corresponding to two orthologue segments of human chromosomes 18, short and long arms. For the examined animals, we excluded the complete coding region and adjacent intronic regions of ovine TGIF1 to harbor disease-causing mutations. CONCLUSIONS: This is the first genetic localization for hereditary ovine isolated microphthalmia. It seems unlikely that a mutation in the TGIF1 gene is responsible for this disorder. The studied sheep represent a valuable large animal model for similar human ocular phenotypes.

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The growing knowledge on physiology, cell biology and biochemistry of the reproductive organs has provided many insights into molecular mechanisms that are required for successful reproduction. Research directed at the investigation of reproduction physiology in domestic animals was hampered in the past by a lack of species-specific genomic information. The genome sequences of dog, cattle and horse have become publicly available in 2005, 2006 and 2007 respectively. Although the gene content of mammalian genomes is generally very similar, genes involved in reproduction tend to be less conserved than the average mammalian gene. The availability of genome sequences provides a valuable resource to check whether any protein that may be known from human or mouse research is present in cattle and/or horse as well. Currently there are more than 200 genes known that are involved in the production of fertile sperm cells. Great progress has been made in the understanding of genetic aberrations that lead to male infertility. Additionally, the first genetic mechanisms are being discovered that contribute to the quantitative variation of fertility traits in fertile male animals. Here, I will review some selected aspects of genetic research in male fertility and offer some perspectives for the use of genomic sequence information.

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Gene duplication is one of the key factors driving genetic innovation, i.e., producing novel genetic variants. Although the contribution of whole-genome and segmental duplications to phenotypic diversity across species is widely appreciated, the phenotypic spectrum and potential pathogenicity of small-scale duplications in individual genomes are less well explored. This review discusses the nature of small-scale duplications and the phenotypes produced by such duplications. Phenotypic variation and disease phenotypes induced by duplications are more diverse and widespread than previously anticipated, and duplications are a major class of disease-related genomic variation. Pathogenic duplications particularly involve dosage-sensitive genes with both similar and dissimilar over- and underexpression phenotypes, and genes encoding proteins with a propensity to aggregate. Phenotypes related to human-specific copy number variation in genes regulating environmental responses and immunity are increasingly recognized. Small genomic duplications containing defense-related genes also contribute to complex common phenotypes.

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An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species approximately 141 thousand years ago (Kya), an exit out-of-Africa approximately 51 Kya, and a recent colonization of the Americas approximately 10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.

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Little is known about the genes and proteins involved in the process of human memory. To identify genetic factors related to human episodic memory performance, we conducted an ultra-high-density genome-wide screen at > 500 000 single nucleotide polymorphisms (SNPs) in a sample of normal young adults stratified for performance on an episodic recall memory test. Analysis of this data identified SNPs within the calmodulin-binding transcription activator 1 (CAMTA1) gene that were significantly associated with memory performance. A follow up study, focused on the CAMTA1 locus in an independent cohort consisting of cognitively normal young adults, singled out SNP rs4908449 with a P-value of 0.0002 as the most significant associated SNP in the region. These validated genetic findings were further supported by the identification of CAMTA1 transcript enrichment in memory-related human brain regions and through a functional magnetic resonance imaging experiment on individuals matched for memory performance that identified CAMTA1 allele-specific upregulation of medial temporal lobe brain activity in those individuals harboring the 'at-risk' allele for poorer memory performance. The CAMTA1 locus encodes a purported transcription factor that interfaces with the calcium-calmodulin system of the cell to alter gene expression patterns. Our validated genomic and functional biological findings described herein suggest a role for CAMTA1 in human episodic memory.

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Osteoarthritis (OA) is a debilitating disease that is becoming more prevalent in today’s society. OA affects approximately 28 million adults in the United States alone and when present in the knee joint, usually leads to a total knee replacement. Numerous studies have been conducted to determine possible methods to halt the initiation of OA, but the structural integrity of the menisci has been shown have a direct effect on the progression of OA. Menisci are two C-shaped structures that are attached to the tibial plateau and aid in facilitating proper load transmission within the knee. The meniscal cross-section is wedge-like to fit the contour of the femoral condyles and help attenuate stresses on the tibial plateau. While meniscal tears are common, only the outer 1/3 of the meniscus is vascularized and has the capacity to heal, hence tears of the inner 2/3rds are generally treated via meniscectomy, leading to OA. To help combat this OA epidemic, an effective biomimetric meniscal replacement is needed. Numerous mechanical and biochemical studies have been conducted on the human meniscus, but very little is known about the mechanical properties on the nano-scale and how meniscal constituents are distributed in the meniscal cross-section. The regional (anterior, central and posterior) nano-mechanical properties of the meniscal superficial layers (both tibial and femoral contacting) and meniscal deep zone were investigated via nanoindentation to examine the regional inhomogeneity of both the lateral and medial menisci. Additionally, these results were compared to quantitative histological values to better formulate a structure-function relationship on the nano-scale. These data will prove imperative for further advancements of a tissue engineered meniscal replacement.

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As water quality interventions are scaled up to meet the Millennium Development Goal of halving the proportion of the population without access to safe drinking water by 2015 there has been much discussion on the merits of household- and source-level interventions. This study furthers the discussion by examining specific interventions through the use of embodied human and material energy. Embodied energy quantifies the total energy required to produce and use an intervention, including all upstream energy transactions. This model uses material quantities and prices to calculate embodied energy using national economic input/output-based models from China, the United States and Mali. Embodied energy is a measure of aggregate environmental impacts of the interventions. Human energy quantifies the caloric expenditure associated with the installation and operation of an intervention is calculated using the physical activity ratios (PARs) and basal metabolic rates (BMRs). Human energy is a measure of aggregate social impacts of an intervention. A total of four household treatment interventions – biosand filtration, chlorination, ceramic filtration and boiling – and four water source-level interventions – an improved well, a rope pump, a hand pump and a solar pump – are evaluated in the context of Mali, West Africa. Source-level interventions slightly out-perform household-level interventions in terms of having less total embodied energy. Human energy, typically assumed to be a negligible portion of total embodied energy, is shown to be significant to all eight interventions, and contributing over half of total embodied energy in four of the interventions. Traditional gender roles in Mali dictate the types of work performed by men and women. When the human energy is disaggregated by gender, it is seen that women perform over 99% of the work associated with seven of the eight interventions. This has profound implications for gender equality in the context of water quality interventions, and may justify investment in interventions that reduce human energy burdens.

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The aging population has become a burning issue for all modern societies around the world recently. There are two important issues existing now to be solved. One is how to continuously monitor the movements of those people having suffered a stroke in natural living environment for providing more valuable feedback to guide clinical interventions. The other one is how to guide those old people effectively when they are at home or inside other buildings and to make their life easier and convenient. Therefore, human motion tracking and navigation have been active research fields with the increasing number of elderly people. However, motion capture has been extremely challenging to go beyond laboratory environments and obtain accurate measurements of human physical activity especially in free-living environments, and navigation in free-living environments also poses some problems such as the denied GPS signal and the moving objects commonly presented in free-living environments. This thesis seeks to develop new technologies to enable accurate motion tracking and positioning in free-living environments. This thesis comprises three specific goals using our developed IMU board and the camera from the imaging source company: (1) to develop a robust and real-time orientation algorithm using only the measurements from IMU; (2) to develop a robust distance estimation in static free-living environments to estimate people’s position and navigate people in static free-living environments and simultaneously the scale ambiguity problem, usually appearing in the monocular camera tracking, is solved by integrating the data from the visual and inertial sensors; (3) in case of moving objects viewed by the camera existing in free-living environments, to firstly design a robust scene segmentation algorithm and then respectively estimate the motion of the vIMU system and moving objects. To achieve real-time orientation tracking, an Adaptive-Gain Orientation Filter (AGOF) is proposed in this thesis based on the basic theory of deterministic approach and frequency-based approach using only measurements from the newly developed MARG (Magnet, Angular Rate, and Gravity) sensors. To further obtain robust positioning, an adaptive frame-rate vision-aided IMU system is proposed to develop and implement fast vIMU ego-motion estimation algorithms, where the orientation is estimated in real time from MARG sensors in the first step and then used to estimate the position based on the data from visual and inertial sensors. In case of the moving objects viewed by the camera existing in free-living environments, a robust scene segmentation algorithm is firstly proposed to obtain position estimation and simultaneously the 3D motion of moving objects. Finally, corresponding simulations and experiments have been carried out.

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Scaphoid is one of the 8 carpal bones found adjacent to the thumb supported proximally by Radius bone. During the free fall, on outstretched hand, the impact load gets transferred to the scaphoid at its free anterior end. Unique arrangement of other carpal bones in the palm is also one of the reasons for the load to get transferred to scaphoid. About half of the total load acting upon carpal bone gets transferred to scaphoid at its distal pole. There are about 10 to 12 clinically observed fracture pattern in the scaphoid due to free fall. The aim of the study is to determine the orientation of the load, magnitude of the load and the corresponding fracture pattern. This study includes both static and dynamic finite element models validated by experiments. The scaphoid model has been prepared from CT scans of a 27 year old person. The 2D slices of the CT scans have been converted to 3D model by using MIMICS software. There are four cases of loading studied which are considered to occur clinically more frequently. In case (i) the load is applied at the posterior end at distal pole whereas in case (ii), (iii) and (iv), the load is applied at anterior end at different directions. The model is given a fixed boundary condition at the region which is supported by Radius bone during the impact. Same loading and boundary conditions have been used in both static and dynamic explicit finite element analysis. The site of fracture initiation and path of fracture propagation have been identified by using max principal stress / gradient and max principal strain / gradient criterion respectively in static and dynamic explicit finite element analysis. Static and dynamic impact experiments were performed on the polyurethane foam specimens to validate the finite element results. Experimental results such as load at fracture, site of fracture initiation and path of fracture propagation have been compared with the results of finite element analysis. Four different types of fracture patterns observed in clinical studies have been identified in this study.