1,579 research outputs found

    p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

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    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours

    Pseudomonas aeruginosa Cystic Fibrosis isolates of similar RAPD genotype exhibit diversity in biofilm forming ability in vitro

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    <p>Abstract</p> <p>Background</p> <p><it>Pseudomonas aeruginosa </it>is considered to grow in a biofilm in cystic fibrosis (CF) chronic lung infections. Bacterial cell motility is one of the main factors that have been connected with <it>P. aeruginosa </it>adherence to both biotic and abiotic surfaces. In this investigation, we employed molecular and microscopic methods to determine the presence or absence of motility in <it>P. aeruginosa </it>CF isolates, and statistically correlated this with their biofilm forming ability <it>in vitro</it>.</p> <p>Results</p> <p>Our investigations revealed a wide diversity in the production, architecture and control of biofilm formation. Of 96 isolates, 49% possessed swimming motility, 27% twitching and 52% swarming motility, while 47% were non-motile. Microtitre plate assays for biofilm formation showed a range of biofilm formation ability from biofilm deficient phenotypes to those that formed very thick biofilms. A comparison of the motility and adherence properties of individual strains demonstrated that the presence of swimming and twitching motility positively affected biofilm biomass. Crucially, however, motility was not an absolute requirement for biofilm formation, as 30 non-motile isolates actually formed thick biofilms, and three motile isolates that had both flagella and type IV pili attached only weakly. In addition, CLSM analysis showed that biofilm-forming strains of <it>P. aeruginosa </it>were in fact capable of entrapping non-biofilm forming strains, such that these 'non-biofilm forming' cells could be observed as part of the mature biofilm architecture.</p> <p>Conclusions</p> <p>Clinical isolates that do not produce biofilms in the laboratory must have the ability to survive in the patient lung. We propose that a synergy exists between isolates <it>in vivo</it>, which allows "non biofilm-forming" isolates to be incorporated into the biofilm. Therefore, there is the potential for strains that are apparently non-biofilm forming <it>in vitro </it>to participate in biofilm-mediated pathogenesis in the CF lung.</p

    Nanofiber fabrication in a temperature and humidity controlled environment for improved fibre consistency

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    To fabricate nanofibers with reproducible characteristics, an important demand for many applications, the effect of controlled atmospheric conditions on resulting electrospun cellulose acetate (CA) nanofibers was evaluated for temperature ranging 17.5 - 35&#xb0;C and relative humidity ranging 20% - 70%. With the potential application of nanofibers in many industries, especially membrane and filter fabrication, their reproducible production must be established to ensure commercially viability.&#xd;&#xa;Cellulose acetate (CA) solution (0.2 g/ml) in a solvent mixture of acetone/DMF/ethanol (2:2:1) was electrospun into nonwoven fibre mesh with the fibre diameter ranging from 150nm to 1&#xb5;m.&#xd;&#xa;The resulting nanofibers were observed and analyzed by scanning electron microscopy (SEM), showing a correlation of reducing average fibre diameter with increasing atmospheric temperature. A less pronounced correlation was seen with changes in relative humidity regarding fibre diameter, though it was shown that increased humidity reduced the effect of fibre beading yielding a more consistent, and therefore better quality of fibre fabrication.&#xd;&#xa;Differential scanning calorimetry (DSC) studies observed lower melt enthalpies for finer CA nanofibers in the first heating cycle confirming the results gained from SEM analysis. From the conditions that were explored in this study the temperature and humidity that gave the most suitable fibre mats for a membrane purpose were 25.0&#xb0;C and 50%RH due to the highest level of fibre diameter uniformity, the lowest level of beading while maintaining a low fibre diameter for increased surface area and increased pore size homogeneity. This study has highlighted the requirement to control the atmospheric conditions during the electrospinning process in order to fabricate reproducible fibre mats

    Revealing emergent magnetic charge in an antiferromagnet with diamond quantum magnetometry

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    Whirling topological textures play a key role in exotic phases of magnetic materials and are promising for logic and memory applications. In antiferromagnets, these textures exhibit enhanced stability and faster dynamics with respect to their ferromagnetic counterparts, but they are also difficult to study due to their vanishing net magnetic moment. One technique that meets the demand of highly sensitive vectorial magnetic field sensing with negligible backaction is diamond quantum magnetometry. Here we show that an archetypal antiferromagnet—haematite—hosts a rich tapestry of monopolar, dipolar and quadrupolar emergent magnetic charge distributions. The direct read-out of the previously inaccessible vorticity of an antiferromagnetic spin texture provides the crucial connection to its magnetic charge through a duality relation. Our work defines a paradigmatic class of magnetic systems to explore two-dimensional monopolar physics, and highlights the transformative role that diamond quantum magnetometry could play in exploring emergent phenomena in quantum materials

    Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis

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    MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE

    Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10–14 year old schoolchildren: the HAPPY study

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    Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness

    Breast imaging technology: Application of magnetic resonance imaging to early detection of breast cancer

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    Since its first introduction approximately 10 years ago, there has been extensive progress in the application of magnetic resonance imaging (MRI) to the detection and diagnosis of breast cancer. Contrast-enhanced MRI has been shown to have value in the diagnostic work-up of women who present with mammogram or clinical abnormalities. In addition, it has been demonstrated that MRI can detect mammogram occult multifocal cancer in patients who present with unifocal disease. Advances in risk stratification and limitations in mammography have stimulated interest in the use of MRI to screen high-risk women for cancer. Several studies of MRI high-risk screening are ongoing. Preliminary results are encouraging

    Constructing living buildings: a review of relevant technologies for a novel application of biohybrid robotics

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    Biohybrid robotics takes an engineering approach to the expansion and exploitation of biological behaviours for application to automated tasks. Here, we identify the construction of living buildings and infrastructure as a high-potential application domain for biohybrid robotics, and review technological advances relevant to its future development. Construction, civil infrastructure maintenance and building occupancy in the last decades have comprised a major portion of economic production, energy consumption and carbon emissions. Integrating biological organisms into automated construction tasks and permanent building components therefore has high potential for impact. Live materials can provide several advantages over standard synthetic construction materials, including self-repair of damage, increase rather than degradation of structural performance over time, resilience to corrosive environments, support of biodiversity, and mitigation of urban heat islands. Here, we review relevant technologies, which are currently disparate. They span robotics, self-organizing systems, artificial life, construction automation, structural engineering, architecture, bioengineering, biomaterials, and molecular and cellular biology. In these disciplines, developments relevant to biohybrid construction and living buildings are in the early stages, and typically are not exchanged between disciplines. We, therefore, consider this review useful to the future development of biohybrid engineering for this highly interdisciplinary application.publishe

    Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

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    The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success
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