The cause of most hypertensive disease is unclear, but inflammation appears critical in disease progression. However, how elevated blood pressure initiates inflammation is unknown, as are the effects of high blood pressure on innate and adaptive immune responses. We now report that hypertensive mice have increased T cell responses to antigenic challenge and develop more severe T cell-mediated immunopathology. A root cause for this is hypertension-induced erythrocyte adenosine 5′-triphosphate (ATP) release, leading to an increase in plasma ATP levels, which begins soon after the onset of hypertension and stimulates P2X7 receptors on antigen-presenting cells (APCs), increasing APC expression of CD86. Hydrolyzing ATP or blocking the P2X7 receptor eliminated hypertension-induced T cell hyperactivation. In addition, pharmacologic or genetic blockade of P2X7 receptor activity suppressed the progression of hypertension. Consistent with the results in mice, we also found that untreated human hypertensive patients have significantly elevated plasma ATP levels compared with treated hypertensive patients or normotensive controls. Thus, a hypertension-induced increase in extracellular ATP triggers augmented APC and T cell function and contributes to the immune-mediated pathologic changes associated with hypertensive disease.
Objective: To examine the shared familial contribution to hippocampal and extrahippocampal morphological abnormalities in patients with sporadic temporal lobe epilepsy (TLE) and their unaffected siblings. Methods: We collected clinical, electrophysiological, and T1-weighted magnetic resonance imaging (MRI) data of 18 sporadic patients with TLE without lesions other than hippocampal sclerosis (12 right, 6 left), their 18 unaffected full siblings, and 18 matched healthy volunteers. We compared between-group differences in cortical thickness and volumes of five subcortical areas (hippocampus, amygdala, thalamus, putamen, and pallidum). We determined the subregional extent of hippocampal abnormalities using surface shape analysis. All our imaging results were corrected for multiple comparisons using random field theory. Results: We detected smaller hippocampal volumes in patients (right TLE: median right hippocampus 1.92 mL, interquartile range [IQR] 1.39-2.62, P < .001; left TLE: left hippocampus 2.05 mL, IQR 1.99-2.33, P = .01) and their unaffected siblings (right hippocampus 2.65 mL, IQR 2.32-2.80, P < .001; left hippocampus 2.39 mL, IQR 2.18-2.53, P < .001) compared to healthy controls (right hippocampus 2.94 mL, IQR 2.77-3.24; left hippocampus 2.71 mL, IQR 2.37-2.89). Surface shape analysis showed that patients with TLE had bilateral subregional atrophy in both hippocampi (right > left). Similar but less-pronounced subregional atrophy was detected in the right hippocampus of unaffected siblings. Patients with TLE had reduced cortical thickness in bilateral premotor/prefrontal cortices and the right precentral gyrus.Siblings did not show abnormalities in cortical or subcortical areas other than the hippocampus. Significance: Our results demonstrate a shared vulnerability of the hippocampus in both patients with TLE and their unaffected siblings, pointing to a contribution of familial factors to hippocampal atrophy. This neuroimaging trait could represent an endophenotype of TLE, which might precede the onset of epilepsy in some individuals. |LONG et aL.
In this paper, for an intensity wavelength division multiplexing (IWDM)-based multipoint fiber Bragg grating (FBG) sensor network, an effective strain sensing signal measurement method, called a long short-term memory (LSTM) machine learning algorithm, integrated with data de-noising techniques is proposed. These are considered extremely accurate for the prediction of very complex problems. Four ports of an optical coupler with distinct output power ratios of 70%, 60%, 40%, and 30% have been used in the proposed distributed IWDM-based FBG sensor network to connect a number of FBG sensors for strain sensing. In an IWDM-based FBG sensor network, distinct power ratios of coupler ports can contain distinct powers or intensities. However, unstable output power in the sensor system due to random noise, harsh environments, aging of the equipment, or other environmental factors can introduce fluctuations and noise to the spectra of the FBGs, which makes it hard to distinguish the sensing signals of FBGs from the noise signals. As a result, noise reduction and signal processing methods play a significant role in enhancing the capability of strain sensing. Thus, to reduce the noise, to improve the signal-to-noise ratio, and to accurately measure the sensing signal of FBGs, we proposed a long short-term memory (LSTM) deep learning algorithm integrated with discrete waveform transform (DWT) data smoother (de-noising) techniques. The DWT data de-noising methods are important techniques for analyzing and de-noising the sensor signals, and it further improves the strain sensing signal measurement accuracy of the LSTM model. Thus, after de-noising the sensor data, these data are fed into the LSTM model to measure the sensing signal of each FBG. The experimental results prove that the integration of LSTM with the DWT data de-noising technique achieved better sensing signal measurement accuracy, even in noisy data or environments. Therefore, the proposed IWDM-based FBG sensor network can accurately sense the signal of strain, even in bad or noisy environments; can increase the number of FBG sensors multiplexed in the sensor system; and can enhance the capacity of the sensor system.
The Teosinte branched 1/Cycloidea/Proliferating cell factor (TCP) domain is an evolutionarily conserved DNA binding domain unique to the plant kingdom. To date, the functions of TCPs have been well studied, but the threedimensional structure of the TCP domain is lacking. Here, we have determined the crystal structure of the TCP domain from OsPCF6. The structure reveals that the TCP domain adopts three short b-strands followed by a helix-loop-helix structure, distinct from the canonical basic helix-loop-helix structure. This folded domain shows high structural similarity to the ribbonhelix-helix (RHH) transcriptional repressors, a family of DNA binding proteins with a conserved 3D structural motif (RHH fold), indicating that TCPs could be reclassified as RHH proteins. Our work will provide insight toward a better understanding of the mechanisms underlying TCP protein function.
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