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Regulation of striatal dopamine release by PLC??1 in dopamine neurons: Involvement of VMAT2 and Synapsin III
No full textDopamine neurons play a pivotal role in voluntary movement, reward learning, and motivation, whose dysfunction is closely related to various psychological and neurodegenerative diseases. Therefore, comprehending the detailed signaling mechanisms that functionally regulate dopamine neurons is indispensable for the development of more effective therapeutic strategies against dopamine-related disorders. In this study, we investigate the physiological role of phospholipase C??1 (PLC??1), one of the key effector enzymes involved in intracellular signaling, on regulating dopaminergic function in vivo. Our findings indicate that cell type-specific deletion of PLC??1 does not adversely affect the morphology and structure of midbrain dopamine neurons. However, it does facilitate dopamine release from dopaminergic axon terminals in the striatum. Elevated dopamine release was accompanied by increased vesicular monoamine transporter 2 (VMAT2) co-localization at dopaminergic axons. Notably, dopamine neuron-specific knockout of PLC??1 also leads to the heightened expression and co-localization of synapsin III, a protein involved in the regulation of synaptic vesicle trafficking. Our findings suggest that PLC??1 in dopamine neurons could play a crucial role in modulating dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III
Efficient finite element reliability analysis employing surrogate model for seismic fragility curve derivation
No full textProbabilistic prediction of structural response of cable bridges based on structural health monitoring data
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Distinct modes of dopaminergic modulation on striatopallidal transmission in health and Parkinsonism
No full textDopamine (DA) and its GPCR receptors control willed movement through the D1-direct pathway and D2-indirect pathway within the basal ganglia. In a classical model, excessive activity in the indirect pathway is one of the circuit mechanisms underlying parkinsonism. Although striatopallidal synapses serve as a critical gateway of the indirect pathway, the physiological functions of dopamine on striatopallidal transmission remain poorly understood. Here, we sought to understand how DA through the nigropallidal pathway modulates striatopallidal transmission. We found that DA is directly released onto the GPe and there is a marked regional heterogeneity of dopaminergic innervation to the GPe. In addition, striatopallidal transmission is physiologically different within the subregions of the GPe defined by the dorsal-ventral and lateral-medial axes. We further showed that dopamine D2-Like receptors modulate striatopallidal transmission via regionally distinct modes of action in the GPe. We also revealed that the differences in subcellular expression and sensitivity of dopamine D2 and D4 receptors expressed on striatopallidal terminals and postsynaptic GPe neurons are likely to make a contribution to the diversity of dopaminergic modulation on striatopallidal transmission throughout the GPe subregions. Notably, nigropallidal dopaminergic innervations to the GPe subregions exhibit differential susceptibility to 6-OHDA. Moreover, 6-OHDA-induced DA depletion particularly promotes D2R-mediated presynaptic inhibition in VL and DM subregions of the GPe. To sum up, these results demonstrate that synaptic information conveyed by the indirect pathway can be differentially regulated by DA via distinct modes of action in the GPe subregions, which can be determined by anatomical locations of striatopallidal synapses
DiffCSP: Finding Browser Bugs in Content Security Policy Enforcement through Differential Testing
No full textA novel approach to measure carbonate alkalinity in aqueous solutions using a total organic carbon analyzer
No full textCarbonate alkalinity is crucial in regulating the pH and buffering capacity of natural water systems. Thus, its accurate measurement is essential to understand various water environments that affect water quality and ecosystem health. However, conventional potentiometric titration has some limitations. It results in inaccurate measurements of carbonate alkalinity when the alkalinity levels are low or when high dissolved organic matter or inorganic ion levels exist. Herein, we propose a novel approach to accurately measure carbonate alkalinity using a total organic carbon (TOC) analyzer. An extensive study comparing the accuracy and reliability of the conventional potentiometric titration method with those of the newly developed TOC method was conducted to develop and verify highly accurate measurements of carbonate alkalinity. The TOC method has several advantages over the conventional potentiometric titration methods, such as its ability to accurately measure carbonate alkalinity in the presence of high dissolved organic matter or inorganic ion levels and its ability to provide rapid and automated measurements with high reproducibility. Because, the limit of detection, limit of quantification, and the variation coefficient of the measurements was 0.016 mM (0.2 mgC/L), 0.050 mM (0.6 mgC/L), and 3.68 % respectively. Thus, the development of a novel TOC method has significant environmental implications as it provides a reliable and accurate means to measure carbonate alkalinity in solutions containing various organic matter types
Electrifying H2O2 synthesis with g-C3N4-based single atom catalysts
No full textThis article highlights the recent work of Zhang, Peng et al. (Nanoscale Horiz., 2023, 8, 695, https://doi.org/10.1039/D2NH00564F) on transition metal single atom embedded graphitic carbon nitride nanosheets for the neutral electrosynthesis of hydrogen peroxide
Poracle: Testing Patches Under Preservation Conditions to Combat the Overfitting Problem of Program Repair
No full textTo date, the users of test-driven program repair tools suffer from the overfitting problem; a generated patch may pass all available tests without being correct. In the existing work, users are treated as merely passive consumers of the tests. However, what if they are willing to modify the test to better assess the patches obtained from a repair tool? In this work, we propose a novel semi-automatic patch-classification methodology named Poracle. Our key contributions are three-fold. First, we design a novel lightweight specification method that reuses the existing test. Specifically, the users extend the existing failing test with a preservation condition???the condition under which the patched and pre-patched versions should produce the same output. Second, we develop a fuzzer that performs differential fuzzing with a test containing a preservation condition. Once we find an input that satisfies a specified preservation condition but produces different outputs between the patched and pre-patched versions, we classify the patch as incorrect with high confidence. We show that our approach is more effective than the four state-of-the-art patch classification approaches. Lastly, we show through a user study that the users find our semi-automatic patch assessment method more effective and preferable than the manual assessment