1,405 research outputs found

    Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.

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    In this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued

    Molecules for memory: modelling CaMKII

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    Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire

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    We provide a detailed description of the rutting vocalisations of free-ranging male Iberian deer (Cervus elaphus hispanicus, Hilzheimer 1909), a geographically isolated and morphologically differentiated subspecies of red deer Cervus elaphus. We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies. Iberian stags give bouts of roars (and more rarely, short series of barks) that are typically composed of two different types of calls. Long Common Roars are mostly given at the beginning or at the end of the bout, and are characterised by a high fundamental frequency (F0) resulting in poorly defined formant frequencies but a relatively high amplitude. In contrast, Short Common Roars are typically given in the middle or at the end of the bout, and are characterised by a lower F0 resulting in relatively well defined vocal tract resonances, but low amplitude. While we did not identify entirely Harsh Roars (as described in the Scottish red deer subspecies (Cervus elaphus scoticus), a small percentage of Long Common Roars contained segments of deterministic chaos. We suggest that the evolution of two clearly distinct types of Common Roars may reflect divergent selection pressures favouring either vocal efficiency in high pitched roars or the communication of body size in low-pitched, high spectral density roars highlighting vocal tract resonances. The clear divergence of the Iberian red deer vocal repertoire from those of other documented European red deer populations reinforces the status of this geographical variant as a distinct subspecies

    Post radiation chylous ascites: a case report

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    We report a 64 years old gentleman with unresectable right-sided retroperitoneal liposarcoma, who underwent radiotherapy & subsequently developed chylous ascites. He failed conservative management of chylous ascites and this was successfully managed with a peritoneovenous shunt. The pathophysiology and management of post radiational chylous ascites is discussed

    The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

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    Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21 , p16 , and p15 and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS

    Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

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    Abstract Background Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. Methods We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. Results and conclusions We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier

    Controlling spin relaxation with a cavity

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    Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the spontaneous emission rate can be strongly enhanced by placing the quantum system in a resonant cavity -an effect which has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, underpinning single-photon sources. Here we report the first application of these ideas to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity of high quality factor and small mode volume, we reach for the first time the regime where spontaneous emission constitutes the dominant spin relaxation mechanism. The relaxation rate is increased by three orders of magnitude when the spins are tuned to the cavity resonance, showing that energy relaxation can be engineered and controlled on-demand. Our results provide a novel and general way to initialise spin systems into their ground state, with applications in magnetic resonance and quantum information processing. They also demonstrate that, contrary to popular belief, the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point where quantum fluctuations have a dramatic effect on the spin dynamics; as such our work represents an important step towards the coherent magnetic coupling of individual spins to microwave photons.Comment: 8 pages, 6 figures, 1 tabl

    Normalising the conversation: a qualitative analysis of player and stakeholder perceptions of menstrual health support within elite female soccer

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    Purpose: This qualitative study explores player and stakeholder perceptions of menstrual health support in elite female soccer. Methods: Semi-structured interviews were conducted with 47 participants including players (n = 12), parents (n = 9), coaches (n = 9), sport scientists (n = 7), nutritionists (n = 5) and medical staff (n = 5). Results: Via thematic analysis, data demonstrate that elite female soccer players experience a range of physical and psychological symptoms primarily at the onset of and during menses (as also perceived by stakeholders), with most participants perceiving these symptoms to impact performance. Nonetheless, menstrual health support is perceived as minimal and although players have their menstrual status tracked, they report little understanding as to why or how this information is used. This confusion was also present among stakeholders, often as a result of uncertainty about the evidence supporting the need for menstrual health support. The perceived lack of support may also be reflective of a culture where conversations about the menstrual cycle are not normalised. Overall, this may result in failure to identify and treat menstrual irregularities despite non-coaching staff members perceiving them to be common amongst players. Conclusion: These data support the need for individualised support based on the lived experiences of individual players and support staff. Furthermore, our research identifies the need for organisational, stakeholder, and player centred education programmes (led by experts in female athlete health) that create an environment where players receive personalised menstrual health support

    Carbohydrate fear, skinfold targets and body image issues: a qualitative analysis of player and stakeholder perceptions of the nutrition culture within elite female soccer

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    Purpose: This qualitative study explores player and stakeholder perceptions of the role of nutrition in supporting player development and performance in elite female soccer. Methods: Semi-structured interviews (36 ± 18 mins in length) were conducted with 47 participants, including players (n = 12), parents (n = 9), coaches (n = 9), sport scientists (n = 7), nutritionists (n = 5) and medical staff (n = 5). Via thematic analysis, data provided an insight into the nutrition culture within elite women’s soccer. Results and conclusions: Data demonstrate that considerable confusion and misconceptions exist amongst players and stakeholders regarding the theoretical underpinning and practical application of meeting energy requirements. As such, it is perceived that players ‘under-fuel’, which is likely caused by misunderstandings about the impact of carbohydrate intake on body composition, a fear of weight gain and the associated impacts upon body image. The ‘carbohydrate fear’ that is experienced by players is exacerbated by external pressures arising from social media, key stakeholders (e.g., coaches) and the skinfold culture surrounding measurement of body composition. Such cultural issues are amplified by the lack of full-time professionally accredited nutritionists overseeing the provision of nutrition support. Indeed, the infrastructure supporting the women’s game (e.g. staffing resource, on-site food provision, player education programmes, etc.) was considered incomparable to the men’s game. When taken together, our data provide a platform for which to develop organisational, stakeholder and player centred education and behaviour change interventions that strive to promote a positive performance nutrition culture within the women’s game
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