51 research outputs found

    Glial Processes at the Drosophila Larval Neuromuscular Junction Match Synaptic Growth

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    Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ), we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non-synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    The role of complex cues in social and reproductive plasticity

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    Phenotypic plasticity can be a key determinant of fitness. The degree to which the expression of plasticity is adaptive relies upon the accuracy with which information about the state of the environment is integrated. This step might be particularly beneficial when environments, e.g. the social and sexual context, change rapidly. Fluctuating temporal dynamics could increase the difficulty of determining the appropriate level of expression of a plastic response. In this review, we suggest that new insights into plastic responses to the social and sexual environment (social and reproductive plasticity) may be gained by examining the role of complex cues (those comprising multiple, distinct sensory components). Such cues can enable individuals to more accurately monitor their environment in order to respond adaptively to it across the whole life course. We briefly review the hypotheses for the evolution of complex cues and then adapt these ideas to the context of social and sexual plasticity. We propose that the ability to perceive complex cues can facilitate plasticity, increase the associated fitness benefits and decrease the risk of costly ‘mismatches’ between phenotype and environment by (i) increasing the robustness of information gained from highly variable environments, (ii) fine-tuning responses by using multiple strands of information and (iii) reducing time lags in adaptive responses. We conclude by outlining areas for future research that will help to determine the interplay between complex cues and plasticity

    Morphological studies of nitric oxide synthase in hamster retina

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    Acta Physiologica Scandinavia, 1999, v. 167 n.2 - Proceedings of the Scandinavian Physiological Society meeting in Umea, 28-30 May 1999

    John Moulder and the Evolution of Model-Based Quantitative Eddy Current NDE

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    John Moulder’s lifetime coincided with a period of exceptionally creative innovation in the theory and practice of eddy current testing (ECT). But, as an unusually gifted experimentalist arriving on the scene at the ideal moment, he contributed far more than his share to the advances made during this period

    Urban regeneration without local government: a case study of post-colonial Hong Kong

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    The near coincidence of the guided wave modes of a plate with zeroes of the reflection coefficient has been used often in the past [1–4] to estimate the plate’s guided wave mode spectrum. Schoch [5] in his quantitative treatment of acoustic reflection from plates expresses the reflected field as a one-dimensional spectral integral over the incident field weighted by the reflection coefficient (RC) and by a propagator term which accounts for diffraction in the incident plane. Bertoni and Tamir [6] later evaluated this integral approximately for an incident Gaussian beam in their analysis of leaky Rayleigh waves. This procedure was later extended to reflection from plates, by Pitts, et al. [7]. Comparisons between numerical or analytical evaluations of this integral formulation of the reflected field and experimental measurements have been made by several authors. A missing element in essentially all these prior treatments, however, is a rigorous analysis of the influence of the receiving transducer

    The role of Id1 in prostate carcinogenesis

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    Nonspecular reflection effects of a bounded ultrasonic beam incident from a liquid onto an elastic structure have been the subject of a great deal of interest during last decades for material characterization [1–10]. It refers to phenomena where the reflected beam has an intensity profile different from that of the incident beam, including a lateral beam displacement, one or several minimum intensity area and a trailing field (Fig. 1). This phenomena occurs when the incident beam is phase-matched to one of the leaky waves supported by the structure. Numerous theoretical studies, based on the calculation of the reflection coefficient, have successfully explained the nonspecular reflection profile of a bounded beam incident at a critical angle [1, 3, 6–10]. In this paper, we present a mode theory for analyzing these nonspecular reflection effects. This approach, which gives a good physical insight, has been recently used to study the excitation of Lamb waves by the a bounded beam [11]

    Structure activity relationships of human galactokinase inhibitors

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    Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDP-galactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibito
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