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Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interac...
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Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families.
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In this paper, we study the queue-overflow probability of wireless scheduling algorithms. In wireless networks operated under queue-length-based scheduling algorithms, there often exists a tight coupling between the service-rate p...
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In this paper, we study the queue-overflow probability of wireless scheduling algorithms. In wireless networks operated under queue-length-based scheduling algorithms, there often exists a tight coupling between the service-rate process, the system backlog process, the arrival process, and the stochastic process governing channel variations. Although one can use sample-path large-deviation techniques to form an estimate of the queue-overflow probability, the formulation leads to a difficult multidimensional calculus-of-variations problem. In this paper, we present a new technique to address this complexity issue. Using ideas from the Lyapunov function approach in control theory, this technique maps the complex multidimensional calculus-of-variations problem to a 1-D calculus-of-variations problem, and the latter is often much easier to solve. Further, under appropriate conditions, we show that when a scheduling algorithm minimizes the drift of a Lyapunov function at each point of every fluid sample path, the algorithm will be optimal in the sense that it maximizes the asymptotic decay rate of the probability that the Lyapunov function value exceeds a given threshold. We believe that these results can potentially be used to study the queue-overflow probability of a large class of wireless scheduling algorithms and to design new scheduling algorithms with optimal overflow probabilities.
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Intestinal immunity exists as a complex relationship among immune cells, epithelial cells, and microbiota. CCR6 and its ligand–CCL20 are highly expressed in intestinal mucosal tissues, such as Peyer’s patches (PPs) and isolated ...
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Intestinal immunity exists as a complex relationship among immune cells, epithelial cells, and microbiota. CCR6 and its ligand–CCL20 are highly expressed in intestinal mucosal tissues, such as Peyer’s patches (PPs) and isolated lymphoid follicles (ILFs). In this study, we investigated the role of the CCR6–CCL20 axis in intestinal immunity under homeostatic conditions. CCR6 deficiency intrinsically affects germinal center reactions in PPs, leading to impairments in IgA class switching, IgA affinity, and IgA memory B cell production and positioning in PPs, suggesting an important role for CCR6 in T-cell-dependent IgA generation. CCR6 deficiency impairs the maturation of ILFs. In these follicles, group 3 innate lymphoid cells are important components and a major source of IL-22, which stimulates intestinal epithelial cells (IECs) to produce antimicrobial peptides (AMPs). We found that CCR6 deficiency reduces IL-22 production, likely due to diminished numbers of group 3 innate lymphoid cells within small-sized ILFs. The reduced IL-22 levels subsequently decrease the production of AMPs, suggesting a critical role for CCR6 in innate intestinal immunity. Finally, we found that CCR6 deficiency impairs the production of IgA and AMPs, leading to increased levels of Alcaligenes in PPs, and segmented filamentous bacteria in IECs. Thus, the CCR6–CCL20 axis plays a crucial role in maintaining intestinal symbiosis by limiting the overgrowth of mucosa-associated commensal bacteria.
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One- and two-way communication with digital compressed visual signals is now an integral part of the daily life of millions. Such commonplace use has been realized by decades of advances in visual signal compression. The design of...
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One- and two-way communication with digital compressed visual signals is now an integral part of the daily life of millions. Such commonplace use has been realized by decades of advances in visual signal compression. The design of effective, efficient compression and transmission strategies for visual signals may benefit from proper incorporation of human visual system (HVS) characteristics. This paper overviews psychophysics and engineering associated with the communication of visual signals. It presents a short history of advances in perceptual visual signal compression, and describes perceptual models and how they are embedded into systems for compression and transmission, both with and without current compression standards.
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Global Navigation Satellite Systems (GNSSs), such as the Global Positioning System (GPS) and Global Navigation Satellite System (GLONASS), are the primary sensors for localization of most unmanned helicopters. However, GNSS signal...
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Global Navigation Satellite Systems (GNSSs), such as the Global Positioning System (GPS) and Global Navigation Satellite System (GLONASS), are the primary sensors for localization of most unmanned helicopters. However, GNSS signals cannot be tracked reliably due to geographic restrictions or deliberate jamming, and this has been an unsolved problem for a long time to localize the position of helicopters robustly and accurately when the GNSS signals are lost. A new algorithm is presented for this unsolved problem based on the unscented Kalman filter (UKF) using measurement data of inertial sensors. The proposed algorithm localizes the position of an unmanned helicopter using three new techniques. First, it models noises of acceleration measurement of inertial sensors by the white noise bias in addition to the commonly used random walking process. Then, this algorithm prioritizes the propagations of states in the UKF. Third, it leverages the time-varying GNSS dilution of precision in line with adjustments of the measurement noise covariances. The combination of these techniques makes it possible to localize the position of unmanned helicopters that are equipped with two-stroke engines, which generate large vibrations that result in noisy acceleration data. To facilitate automated tuning of the filter parameters, we further develop a population-based tuning method. The proposed algorithm with the auto-tuning method enables the positioning of unmanned helicopters and prompt reaction in the case of a GNSS outage without requiring tedious manual calibrations. The performance of this algorithm is experimentally validated on a fully instrumented model-sized helicopter.
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The domain Archaea is composed of several subdomains, and prominent among them are the Crenarchaeota and the Euryarchaeota. Biochemically characterized archaeal family Y DNA polymerases (Pols) or DinB homologs, to date, are all fr...
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The domain Archaea is composed of several subdomains, and prominent among them are the Crenarchaeota and the Euryarchaeota. Biochemically characterized archaeal family Y DNA polymerases (Pols) or DinB homologs, to date, are all from crenarchaeal organisms, especially the genus Sulfolobus. Here, we demonstrate that archaeal family Y Pols fall into five clusters based on phylogenetic analysis. MacDinB-1, the homolog from the euryarchaeon Methanosarcina acetivorans that is characterized in this study, belongs to cluster II. Therefore, MacDinB-1 is different from the Sulfolobus DinB proteins, which are members of cluster I. In addition to translesion DNA synthesis activity, MacDinB-1 synthesized unusually long products ( approximately 7.2 kb) in the presence of its cognate proliferating cell nuclear antigen (PCNA). The PCNA-interacting site in MacDinB-1 was identified by mutational analysis in a C-terminally located heptapeptide akin to a PIP (PCNA-interacting protein) box. In vitro assays from the present report suggested that MacDinB-1 works in an error-free mode to repair cyclobutane pyrimidine dimers. This study on a euryarchaeal DinB homolog provides important insights into the functional diversity of the family Y Pols, and the availability of a genetic system for this archaeon should allow subsequent elucidation of the physiological significance of this enzyme in M. acetivorans cells.
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Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other are...
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Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca2+-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses. We found that the NMDA glutamatergic antagonist D,L-2-amino-5-phosphonovaleric acid (APV; 50 μM) reduced both the area and duration of the bursts at both proximal and distal synapses by about half. The L-type Ca2+ channel blocker nimodipine (10 μM) and the R- and T-type Ca2+ channel blocker NiCl2 (200 μM) decreased the area of the bursts to a lesser extent; none of these effects appeared to be location-dependent. Remarkably, the perfusion of flufenamic acid (FFA; 100 μM), to block Ca2+-activated non-selective cation currents (ICAN) mediated by transient receptor potential (TRP) channels, had a location-dependent effect, by abolishing burst firing and switching the suprathreshold response to a single action potential (AP) for proximal stimulation, but only minimally affecting the bursts evoked by distal stimulation. A similar outcome was found when FFA was pressure-applied locally around the proximal dendrite of the recorded neurons and in the presence of a selective blocker of melastatin TRP (TRPM) channels, 9-phenanthrol (100 μM), whereas a selective blocker of canonical TRP (TRPC) channels, SKF 96365, did not affect the bursts. These results indicate that different mechanisms might contribute to the initiation of hyperexcitability in layer V neurons at proximal and distal synapses and could shed light on the initiation of epileptiform activity in the entorhinal cortex.
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L-type calcium channels play an essential role in synaptic activity-dependent gene expression and are implicated in long-term alterations in synaptic efficacy underlying learning and memory in the hippocampus. The two principal po...
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L-type calcium channels play an essential role in synaptic activity-dependent gene expression and are implicated in long-term alterations in synaptic efficacy underlying learning and memory in the hippocampus. The two principal pore-forming subunits of L-type Ca2+ channels expressed in neurons are the Ca(v)1.2 (alpha(1C)) or Ca(v)1.3 (alpha(1D)) subtypes. Experimental evidence suggests that calcium entry through Ca(v)1.2 and Ca(v)1.3 Ca2+ channels occurs in close proximity to key signalling molecules responsible for triggering signalling pathways leading to transcriptional responses. Determining the subcellular distribution of Ca(v)1.2 and Ca(v)1.3 L-type channels in neurons is clearly important for unravelling the molecular mechanisms underlying long-term alterations in neuronal function. In this study, we used immunogold-labelling techniques and electron-microscopy (EM) to analyse the subcellular distribution and density of both Ca(v)1.2 and Ca(v)1.3 Ca2+ channels in rat hippocampal CA1 pyramidal cells in vivo. We confirm that both Ca(v)1.2 and Ca(v)1.3 channel subtypes are predominantly but not exclusively located in postsynaptic dendritic processes and somata. Both Ca(v)1.2 and Ca(v)1.3 are distributed throughout the dendritic tree. However, the smallest (distal) dendritic processes and spines have proportionally more calcium channels inserted into their plasma membrane than located within cytoplasmic compartments indicating the potential targeting of calcium channels to microdomains within neurons. Ca(v)1.2 and Ca(v)1.3 Ca2+ channels are located at the postsynaptic density and also at extra-synaptic sites. The location of L-type Ca(v)1.2 and Ca(v)1.3 channels in distal dendrites and spines would thus place them at appropriate sites where they could initiate synapse to nucleus signalling.
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Malignant astrocytoma is the most commonly occurring brain tumour in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumour suppressive effect in basic researc...
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Malignant astrocytoma is the most commonly occurring brain tumour in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumour suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumours. Here we analysed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients. SOD1 expression, SOD1 activity, and SOD1 protein level were lower in Grade IV astrocytomas. SOD2 expression was lower in low-grade (Grades I and II) and Grade III astrocytomas than in controls, but SOD2 expression and SOD2 protein level were higher in Grade IV astrocytomas than in Grade III astrocytomas. Although there was no change in SOD2 activity and a lower activity of citrate synthase (CS), the MnSOD:CS ratio increased in Grade IV astrocytomas compared with controls and low-grade astrocytomas. Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy. Lower SOD2:CS ratio was associated with poor outcomes for Grade IV astrocytomas. This is the first study to quantify changes of various primary antioxidant enzymes in different grades of astrocytomas at different levels concurrently in human astrocytomas. ?2018, ?2018 Informa UK Limited, trading as Taylor & Francis Group.
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Mitochondrial dysfunction and oxidative stress are underlying contributors to Parkinsons disease (PD). The reduction of aberrant proteins and dysfunctional mitochondria through constitutive autophagy is essential for neuronal surv...
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Mitochondrial dysfunction and oxidative stress are underlying contributors to Parkinsons disease (PD). The reduction of aberrant proteins and dysfunctional mitochondria through constitutive autophagy is essential for neuronal survival. We investigated the neuroprotective effects of the natural red wine extract, resveratrol, on the Complex I inhibitor, rotenone-induced oxidative stress SH-SY5Y cellular model. With rotenone exposure, cellular reactive oxygen species (ROS), apoptosis and cell death increased at both 6 and 18 h; at the same time, mitochondrial membrane potential (敤m) and the balance of mitochondrial dynamic proteins were disrupted, resulting with fragmented mitochondria. Rotenone was also noted to elevate autophagy initiation but downregulate the autophagy flux. Pretreatment with resveratrol to rotenone exposed cells lowered cellular ROS, apoptosis, and increased survival rates. Resveratrol administration also recovered rotenone induced 敤m, mitochondria dynamics alteration, and elongated fragmented mitochondria. Both autophagic induction and autophagic flux were enhanced with resveratrol pre-treatment which is compatible with cellular survival. The mitogen-activated protein kinase (MEK) inhibitor, U0126, abolished the rescuing effect of resveratrol on rotenone treated neurons through the inhibition of autophagy flux. Thus, our work implies that the neuroprotective effect of resveratrol works in part through modulation of mitochondria dynamics and upregulating autophagic flux via the MEK/extracellular signal-regulated kinase (ERK) signalling pathway. ?2019, ?2019 Informa UK Limited, trading as Taylor & Francis Group.
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