1,081 research outputs found

    APC/C–Cdc20-mediated degradation of cyclin B participates in CSF arrest in unfertilized Xenopus eggs

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    AbstractIn vertebrates, unfertilized eggs are arrested at meiotic metaphase II (meta-II) by cytostatic factor (CSF), with Cdc2 activity maintained at a constant, high level. CSF is thought to suppress cyclin B degradation through the inhibition of the anaphase-promoting complex/cyclosome (APC/C)-Cdc20 while cyclin B synthesis continues in unfertilized eggs. Thus, it is a mystery how Cdc2 activity is kept constant during CSF arrest. Here, we show that the APC/C–Cdc20 can mediate cyclin B degradation in CSF-arrested Xenopus eggs and extracts, in such a way that when Cdc2 activity is elevated beyond a critical level, APC/C–Cdc20-dependent cyclin B degradation is activated and Cdc2 activity consequently declines to the critical level. This feedback control of Cdc2 activity is shown to be required for keeping Cdc2 activity constant during meta-II arrest. We have also shown that Mos/MAPK pathway is essential for preventing the cyclin B degradation from inactivating Cdc2 below the critical level required to sustain meta-II arrest. Our results indicate that under CSF arrest, Mos/MAPK activity suppresses cyclin B degradation, preventing Cdc2 activity from falling below normal meta-II levels, whereas activation of APC/C–Cdc20-mediated cyclin B degradation at elevated levels of Cdc2 activity prevents Cdc2 activity from reaching excessively high levels

    Altered connectivity of the right anterior insula drives the pain connectome changes in chronic knee osteoarthritis

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    Resting-state functional connectivity (FC) has proven a powerful approach to understand the neural underpinnings of chronic pain, reporting altered connectivity in three main networks: the default mode (DMN), central executive (CEN), and the salience network (SN). The interrelation and possible mechanisms of these changes are less well understood in chronic pain. Based on emerging evidence of its role to drive switches between network states, the right anterior insula (rAI, an SN hub) may play a dominant role in network connectivity changes underpinning chronic pain. To test this hypothesis, we used seed-based resting-state FC analysis including dynamic and effective connectivity metrics in 25 people with chronic osteoarthritis (OA) pain and 19 matched healthy volunteers. Compared to controls, participants with painful knee OA presented with increased anticorrelation between the right anterior insula (SN) and DMN regions. Also, the left dorsal prefrontal cortex (CEN hub) showed more negative FC with the right temporal gyrus. Granger causality analysis revealed increased negative influence of the right anterior insula on the posterior cingulate (DMN) in OA patients in line with the observed enhanced anticorrelation. Moreover, dynamic FC was lower in the DMN of patients and thus more similar to temporal dynamics of the SN. Together, these findings evidence a widespread network disruption in patients with persistent osteoarthritis pain, and point toward a driving role of the rAI

    Outside interference or Hong Kong embracing its unique identity? : The Chinese Universities Shakespeare Festival

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    Ongoing clashes between Hong Kong citizens and its government have foregrounded questions about outside interference in Hong Kong’s politics (largely from the government and media of People’s Public of China), as well as debate about what institutions in Hong Kong are neo-colonial, heavily inflected with nostalgia for British colonialism, or in the process of being ‘colonised’ by the People’s Republic of China. This article looks at Shakespeare in Hong Kong (and, to some extent, greater Chinese) theatre and education as one of those contested institutions, using the particular case of the now-defunct Chinese Universities Shakespeare Festival. The author probes their initial, surface impression of the festival as a simple outpouring of colonial sentiment and impulse, using its sizeable archives to realise a reading of the institution that highlights the complexities of international and intra-regional politics, culture and identity in Hong Kong and greater China. It builds on the Hong Kong literary critic Michael Ingham’s call for attention to Hong Kong’s quest – sometimes overt (as in the demonstrations of 2019), sometimes implicit (in the body of literature Ingham explores in his cultural and literary history) – for a unique, post-colonial identity that is inspired – but, critically, not confined – by its Chinese and British histories. The article briefly outlines the origins and set-up of the festival before juxtaposing the dominance of English language and culture in it with the opportunities it presents (seized by several teams) for intra-regional cooperation, competition and sharing diverse, greater Chinese cultures. The article offers a model for critically appraising other institutions and cultural products in Hong Kong in ways that resist easy binaries of British or Chinese, colonial or indigenous

    Multiplication and Composition in Weighted Modulation Spaces

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    We study the existence of the product of two weighted modulation spaces. For this purpose we discuss two different strategies. The more simple one allows transparent proofs in various situations. However, our second method allows a closer look onto associated norm inequalities under restrictions in the Fourier image. This will give us the opportunity to treat the boundedness of composition operators.Comment: 49 page

    Effect of intersubband scattering on weak localization in 2D systems

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    The theory of weak localization is generalized for multilevel 2D systems taking into account intersubband scattering. It is shown that weak intersubband scattering which is negligible in a classical transport, affects strongly the weak-localization correction to conductivity. The anomalous magnetoresistance is calculated in the whole range of classically low magnetic fields. This correction to conductivity is shown to depend strongly on the ratios of occupied level concentrations. It is demonstrated that at relatively low population of the excited subband, it is necessary to use the present theory because the high-field limit asimptotics is shown to be achieved only in classical magnetic fields.Comment: 18 pages, 4 figures. Accepted to Phys. Rev. B 6

    Application of PDT for Uterine Cervical Cancer

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    We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL)

    Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain?

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    Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10 ”g/50 ”l; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1 mg/50 ”l; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7 T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72 mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5 g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats
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