41,548 research outputs found

    Building body identities - exploring the world of female bodybuilders

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    This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances

    Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole

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    Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates

    Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder.

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    Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome

    Investigating the potential role for RBMY in cancer

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    Introduction: Head and neck squamous cell carcinoma (HNSCC), is a major healthcare concern with a high male prevalence. We hypothesise that the testis specific mRNA splicing regulator, Y-linked RBMY gene, is aberrantly expressed in HNSCC in part promoting HNSCC through ZFY-short splicing. RBMY has been shown to enhance tumour development in male hepatocellular carcinoma (human tissue specimens and transgenic-mouse models) whilst ZFY-short is predicted to have anti-apoptotic properties and the deletion of RBMY locus on Y-chromosome resulted in lowered ZFY-short expression. Thus, we hypothesize that ZFY-short is generated by RBMY and exerts its anti-apoptotic effects to promote male HNSCC. Methods: Due to the coronavirus lockdown, bench work was restricted to 6 months, therefore, I conducted an extended analysis of RBMY expression in human cancer, including a computational analysis of RBMY gene expression with data from the cBioPortal database. In my bench-work, I attempted to establish GFP- RBMY expressing cell lines and conducted fluorescence microscopy, RT- PCR and qPCR to analyse RBMY expression in HNSCC cell lines and its impact on ZFY-short expression. Results: RBMY is expressed in several cancers, with no driver mutations. RBMY has nuclear localisation and is expressed in 93-UV-147T and UM-SCC-104 cell lines (both HPV16-positive HNSCC cell lines), with increased ZFY-short expression observed in UM- SCC-104. Discussion: Despite RBMY having been shown to be an oncogene in male liver cancer, our analysis of cBioPortal data suggests this activity may be restricted to the small minority of tumours of different cancer types that express RBMY. The paralleled expression of RBMY and ZFY-short in our cell lines indicate an association. UMSCC104 cell line originates from a highly an aggressive and recurrent tumour, RBMY is associated with tumour stemness, thus it is possible that via ZFY-short, RBMY could have promoted the aggressive phenotype in this, and in other HNSCCs

    Modificaciones de la variabilidad de la frecuencia cardíaca producidas en un modelo experimental de síndrome metabólico

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    Antecedentes: El síndrome metabólico (SM) se define como el conjunto de al menos tres de las siguientes condiciones: obesidad central, elevación de triglicéridos, disminución de lipoproteínas de alta densidad, hipertensión sistémica e intolerancia a la glucosa. El SM está relacionado con una alta prevalencia de enfermedades cardiovasculares, muerte súbita cardíaca y arritmias auriculares, eventos que pueden ser consecuencia de cambios relacionados con la estructura, función y control del corazón. Uno de los mecanismos subyacentes podría ser la alteración de la automaticidad del nodo sinusal por alteraciones del sistema nervioso autónomo qué pueden evaluarse analizando los componentes de la variabilidad de la frecuencia cardíaca (VFC). Objetivo: Examinar las modificaciones de la VFC, su evolución y su posible relación con los diferentes componentes del síndrome metabólico en un modelo experimental en conejo, inducido por la administración de una dieta alta en grasa y azúcar. Métodos: Se asignaron al azar conejos machos NZW al grupo control (n = 10) o al grupo SM (n = 10), alimentados con una dieta rica en grasas (10% de aceite de coco y 5% de manteca de cerdo) y alta en sacarosa (15% disuelta en agua). durante 28 semanas. Se registró un ECG durante 15 minutos antes de la administración de la dieta, en las semanas 14 y 28. En la semana 28, se realizó un registro de ECG de 24 horas (eMotion Faros 180, Mega Electronics®, 1 kHz). Luego se aislaron estos corazones, se estabilizaron durante 15 minutos y se registraron electrogramas de 15 minutos de duración en un sistema de tipo Languendorff. Analizamos las oscilaciones RR in vivo de corta y larga duración, y en corazón aislado, en los dominios del tiempo, la frecuencia y el análisis no lineal. Para el análisis estadístico se utilizó el análisis multivariado de varianza (MANOVA, modelo factorial) (p <0,05). Resultados análisis de corta duración: El análisis del dominio de la frecuencia de la VFC mostró un aumento en el componente de HF en los animales con SM en la semana 28 (p 0,05) en MSE mínimo y máximo, así como en el CI1-20 con predominio en la semana 14. Los demás parámetros del análisis no lineal no mostraron cambios estadísticamente significativos. Resultados análisis de larga duración: El análisis en el dominio del tiempo mostró una disminución en el intervalo RR y el Ti geométrico (p>0,005) en animales con SM, indicativo de un aumento de la FC. El resto de parámetros en el dominio del tiempo analizados no se modificaron. En el dominio de la frecuencia en el espectro FFT, encontramos una disminución significativa en la banda LF (p = 0.032) en animales SM. El resto de los parámetros del dominio de la frecuencia (índice VLF, HF y LF / HF) se mantuvo sin cambios. El análisis de Poincaré mostró un aumento del índice SD1 / SD2 en animales con SM durante el día y la noche en comparación con los controles (p = 0.043). Además, encontramos una disminución de DFAα1 (p = 0.021) y DFAα2 (p = 0.002) en animales SM. Se encontró la misma tendencia en MSEmax (p = 0.014) para el grupo SM. No se observaron cambios significativos en el resto de componentes de los análisis no lineales. Resultados análisis en corazón aislado: En el dominio de la frecuencia, encontramos un aumento en el componente LF de VFC en animales con SM y la relación LF / HF (p <0.05), pero el resto de los parámetros del dominio de la frecuencia permanecieron sin cambios. Con respecto al análisis no lineal, la ApEn; (p <0.05) y el mínimo de entropía multiescala (p <0.05) disminuyó en grupo SM. No se encontraron diferencias en ninguno de los parámetros estándar del dominio del tiempo. Conclusiones: El SM produjo cambios significativos en el análisis de la VFC de corta duración, en el dominio del tiempo y la frecuencia, lo que sugiere aumento de la actividad simpática y alteración barorefleja respectivamente, aspectos que podrían predisponer a un mayor riesgo cardiometabolico y muerte súbita. Con respecto al análisis de larga duración observamos aumentos de la FC tanto en el dia como en la noche, lo que indica la perdida del equilibrio autonómico y se asocia a patrones arrítmicos. Además, el análisis no lineal muestra una coactivación aleatoria y perdida del equilibrio simpático-vagal, reflejado en el descenso de DFAα-1, DFAα-2, y la entropía. Finalmente, el análisis de la VFC en el corazón aislado mostró un descenso de la concentración espectral, indicativo de una mayor heterogeneidad de altas y bajas frecuencias y permitió observar el aumento de la entropía que apunta a una mayor irregularidad del control intrínseco cardiaco

    Nuclear spatial organization influences centromere identity

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    Centromeres are specialized chromosomal domains that provide the attachment site for spindle microtubules emanating from opposite spindle pole bodies (SPBs; centrosome equivalent). Centromere identity is epigenetically defined by the histone H3-variant, CENP-A. Both genetic and epigenetic factors influence the de novo assembly of CENP-A. In the fission yeast, Schizosaccharomyces pombe, CENP-ACnp1 (Cnp1, ortholog of human CENP-A) chromatin prefers to establish on centromere central domain DNA, but it also can assemble on non-centromeric DNA in rare situations. Adjacent heterochromatin, formed over flanking outer repeats, is required to establish CENP-ACnp1 chromatin on central domain, but overexpression of CENP-ACnp1 can bypass this requirement. All constitutive heterochromatic loci (centromeres, telomeres and mating-type regions and synthetic heterochromatin) preferentially localize to the nuclear envelope (NE) or SPB. Newly synthesized CENP-ACnp1 replaces S-phase deposited placeholder H3 when it is incorporated during the subsequent G2 phase into centromeric central domain chromatin which is transcribed by RNAPII (RNA polymerase II). These observations suggest that heterochromatin might influence CENP-ACnp1 chromatin establishment by modifying central domain chromatin properties or exposing it to favorable nuclear locations for CENP-ACnp1 assembly. All three centromeres are clustered at the SPBs and centromere-associated CENP-ACnp1 assembly factors including HJURPScm3, RbAP46/48Mis16, Mis18, Eic1/Mis19 are all concentrated at this location in G2 when new CENP-ACnp1 is incorporated. The aim of my thesis is to investigate the influence of nuclear positioning of heterochromatin on CENP-ACnp1 establishment in fission yeast. I show that minichromosomes carrying heterochromatic outer repeats are located close to SPBs during interphase, consistent with this location influencing CENP-ACnp1 incorporation. CENP-ACnp1 is established on central domain inserted in cis close to, but not far away from, functional endogenous centromeres or neocentromeres. Neocentromeres also join the centromere cluster at SPBs during interphase. CENP-ACnp1 establishment is not dependent on the local chromatin context or DNA sequence at insertion sites. Moreover, direct tethering of central domain-bearing plasmids in trans to SPBs promotes de novo CENP-ACnp1 and kinetochore proteins assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation. Heterochromatin is not required for the establishment of CENP-ACnp1 on central domain placed in cis or trans close to the SPB-centromere clusters. Collectively, I conclude that heterochromatin mediates the association of adjacent central domain with SPBs thus exposing it to high concentrations of CENP-ACnp1 and associated assembly factors to promote de novo CENP-ACnp1 chromatin and kinetochores assembly. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity

    Modelling extraterrestrial habitability, biomass and biosignatures through the bioenergetic lens

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    In order to survive, evolve and thrive, life requires a biologically useful supply of energy and nutrients. While there is evidence for both throughout the solar system and beyond, quantifying the energetic threshold at which a given environment can be described as habitable remains difficult. This thesis explores how power (energy per unit time) can be used as a habitability predictor in extraterrestrial environments. The behaviour of life is simplified into a series of chemical processes which use energy and nutrients to create and maintain complexity — order from disorder — all while obeying the fundamental laws of thermodynamics. Crucially, the underlying thermodynamics of biology is split into two clear habitability-defining terms: the available power supply and the power demand posed by the environment. We developed a new computational model for assessing the energetic and nutrient availability of the weakly constrained environments that are typical of astrobiology, astronomy and planetary science. NutMEG [Nutrients, Maintenance, Energy and Growth] can be used to estimate how much biomass an environment could provide were it exposed to life and how a microbial community might affect the local chemistry. We used the model to characterise the behaviour of methanogens in optimal conditions, and examine how the predictions change in energy- or nutrient-limited settings. For this application, NutMEG was configured to replicate methanogen growth behaviour from laboratory data available in the literature. As temperature rises from 280 to 330 K, NutMEG predicts exponential drops in final biomass (109–106 cells/L) and total methane production from a growth cycle (62–3 μM) despite an increase in peak growth rates (0.007–0.14 /hr). This owes to the increasing cost of survival diverting energy away from growth processes. Restricting energy and nutrients exacerbates this trend. With minimal assumptions NutMEG can reliably replicate microbial growth behaviour, but better understanding of the synthesis and maintenance costs life must overcome in different extremes is required to improve its results further. We used NutMEG to examine the habitability of Enceladus’ subsurface ocean. The oceanic composition is difficult to characterise with current data and estimates are highly dependent on model-based interpretations, informed by Cassini measurements, which are also not yet tightly constrained. In light of these ambiguities, we considered a wide selection of parameter spaces to quantify the available energy for putative methanogens on Enceladus. We estimated the spontaneous power supply their metabolism could provide and compared it to expected power demands in order to map the icy moon’s habitability. On the one hand, Enceladus’ parameter space contains pockets in which life could thrive. On the other, there are swathes of the parameter space which appear uninhabitable. Enceladean habitability appears to be a delicate balance between the ocean’s temperature, pH, salinity and concentrations of carbonates, nutrients and dissolved gases (particularly H2); many of which are co-dependent. Variation in any one of these can tip the balance into uninhabitable conditions. These results do not aim to be pessimistic, but reflect how astrobiologists should be cautiously pragmatic in their approach to calculating the theoretical habitability of bodies which are not yet well characterised. Finally, we extend this to explore the energetic controls on possible biomass and biosignatures on Enceladus. Peak methanogenic growth rates and biomass estimates for the ocean’s parameter space are defined, ranging from completely devoid of life to bustling with biology. We then consider hydrothermal activity as a source of hydrogen and carbon dioxide and quantify how this could improve methanogens’ chances of survival in Enceladus’ ocean. Using measurements from the Cassini mission and predictions of hydrothermal productivity we constrain the levels of biomass which could be supported in the bulk ocean in a steady state and discuss whether associated biosignatures could be detectable with future instruments. Much of the ocean is inflexible to small changes in biological behaviour, implying that methanogens fitting neatly into such conditions is improbable. However, some pockets of the parameter space at pH 8.5–9 are flexible, and tantalisingly coincide with the current best estimate of bulk ocean pH. In such regions, methanogens could occupy habitable niches in an ocean which behaves as-observed with biomasses of up to ∼10^10 cells/L, but this requires such life to be near the H2 source. Whether biosignatures could be detectable via an amino acid chirality analysis depends on the temperature of the habitat and the flow of material through the ocean, neither of which are understood well enough to draw concrete conclusions yet. At hydrothermal temperatures >370 K these biosignatures decay within months, but in the cool bulk ocean they could be preserved for millennia
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