8,220 research outputs found

    Bardet-Biedl syndrome proteins control cilia length through regulation of actin polymerisation.

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    Primary cilia are cellular appendages important for signal transduction and sensing the environment. Bardet-Biedl syndrome proteins form a complex that is important for several cytoskeleton-related processes such as ciliogenesis, cell migration and division. However, the mechanisms by which BBS proteins may regulate the cytoskeleton remain unclear. We discovered that Bbs4 and Bbs6 deficient renal medullary cells display a characteristic behaviour comprising poor migration, adhesion and division with an inability to form lamellipodial and filopodial extensions. Moreover, fewer mutant cells were ciliated (48% ± 6 for wild-type cells vs 23% ± 7 for Bbs4 null cells; P-value < 0.0001) and their cilia were shorter (2.55&emsp14;μm ± 0.41 for wild-type cells vs 2.16&emsp14;μm ± 0.23 for Bbs4 null cells; P-value < 0.0001). Whilst the microtubular cytoskeleton and cortical actin were intact, actin stress fibre formation was severely disrupted, forming abnormal apical stress fibre aggregates. Furthermore, we observed over-abundant focal adhesions in Bbs4, Bbs6 and Bbs8-deficient cells. In view of these findings and the role of RhoA in regulation of actin filament polymerisation, we showed that RhoA-GTP levels were highly upregulated in the absence of Bbs proteins. Upon treatment of Bbs4-deficient cells with chemical inhibitors of RhoA, we were able to restore cilia length and number as well as the integrity of the actin cytoskeleton. Together these findings indicate that Bbs proteins play a central role in the regulation of the actin cytoskeleton and control cilia length through alteration of RhoA levels

    P2X receptors as targets for the treatment of status epilepticus.

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    Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate Îł-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection

    Environmental changes and radioactive traces

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    Active galactic nuclei synapses: X-ray versus optical classifications using artificial neural networks

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    (Abridged) Many classes of active galactic nuclei (AGN) have been defined entirely throughout optical wavelengths while the X-ray spectra have been very useful to investigate their inner regions. However, optical and X-ray results show many discrepancies that have not been fully understood yet. The aim of this paper is to study the "synapses" between the X-ray and optical classifications. For the first time, the new EFLUXER task allowed us to analyse broad band X-ray spectra of emission line nuclei (ELN) without any prior spectral fitting using artificial neural networks (ANNs). Our sample comprises 162 XMM-Newton/pn spectra of 90 local ELN in the Palomar sample. It includes starbursts (SB), transition objects (T2), LINERs (L1.8 and L2), and Seyferts (S1, S1.8, and S2). The ANNs are 90% efficient at classifying the trained classes S1, S1.8, and SB. The S1 and S1.8 classes show a wide range of S1- and S1.8-like components. We suggest that this is related to a large degree of obscuration at X-rays. The S1, S1.8, S2, L1.8, L2/T2/SB-AGN (SB with indications of AGN), and SB classes have similar average X-ray spectra within each class, but these average spectra can be distinguished from class to class. The S2 (L1.8) class is linked to the S1.8 (S1) class with larger SB-like component than the S1.8 (S1) class. The L2, T2, and SB-AGN classes conform a class in the X-rays similar to the S2 class albeit with larger fractions of SB-like component. This SB-like component is the contribution of the star-formation in the host galaxy, which is large when the AGN is weak. An AGN-like component seems to be present in the vast majority of the ELN, attending to the non-negligible fraction of S1-like or S1.8-like component. This trained ANN could be used to infer optical properties from X-ray spectra in surveys like eRosita.Comment: 15 pages, 7 figures, accepted for publication in A&A. Appendix B only in the full version of the paper here: https://dl.dropboxusercontent.com/u/3484086/AGNSynapsis_OGM_online.pd

    Bioremoval of Phenol from Aqueous Solutions Using Native Caribbean Seaweed

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    Among several Puerto Rican algae, Sargassum sp. (SG) and Chaetomorpha (CM) showed the highest phenol adsorption capacity from aqueous solutions and were used in optimized adsorption batch experiments at room temperature. The effects of pH, adsorbent dose, phenol concentration, salinity and presence of interfering substances were evaluated. Initial solution pH exhibited a strong effect, mainly on the phenol aqueous chemistry; showing the maximum adsorption at pH 10. Sorption isotherm results were modelled according to the Langmuir, Tempkin and Freundlich equations. Isotherm modelling indicated a maximum adsorption capacity (qmax) of 82.10 and 17.7 mg of phenol per gram of SG and CM, respectively. Salinity and presence of detergent in the matrix solution showed a positive effect on the adsorption, suggesting that adsorption of phenol was mostly driven by polar forces and not by ionic exchange. On the other hand, presence of heavy metals like copper, lead and cobalt had a negative effect on the adsorption. According to these results, the potential formation of hydrogen bonds between the algae and phenol is proposed as the main adsorption mechanism. These results provide further insight into the adsorption mechanism of phenol and their use as inexpensive adsorbents for the treatment of phenol-containing wastewaters

    Bluetooth Mesh Analysis, Issues, and Challenges

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    BLE is a widely used short-range technology which has gained a relevant position inside the Internet-of-Things (IoT) paradigm development thanks to its simplicity, low-power consumption, low-cost and robustness. New enhancements over BLE have focused on supporting mesh network topology. Compared to other mesh networks, BLE mesh has only considered a managed flooding protocol in its first version. Managed flooding may generally seem inefficient in many contexts, but it is a high desirable option when data transmission is urgent, the network is small or its configuration changes in a very dynamic way. Knowing the interest to many application contexts, this paper analyses the impact of tweaking several features over the reliability and efficiency of the mesh network. These features are configured and controlled in different layers: message repetition schemes, the transmission randomization, the election of a scheme based on an acknowledged or unacknowledged transmission, etc. In order to estimate the real performance of a mesh network deployment, this paper evaluates the effects of the interaction of the chosen parameters, their appropriate adjustment in relation with the characteristics of real implementations and the true overhead related to the whole protocol stack. The paper identifies configuration challenges, proposes network tuning criteria and outlines possible standard improvements. For this purpose, a detailed assessment on the implementation and execution of real devices has been performed with their chipset limitations
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