In this paper, we prove the unique existence of global strong solutions and decay estimates for the simplified Ericksen–Leslie system describing compressible nematic liquid crystal flows in RN, ...3≤N≤7. Firstly, we rewrite the system in Lagrange coordinates, and secondly, we prove the global well-posedness for the transformed system, which is the main task in this paper. The proof is based on the maximal Lp-Lq regularity and the Lp-Lq decay estimates to the linearized problem.
We consider the uniqueness of ground states for combined power-type nonlinear scalar field equations involving the Sobolev critical exponent at high frequencies. The uniqueness of ground states at ...high frequencies in five and higher dimensions has been proved in Akahori et al. (Calc. Var. Partial Differential Equations 58:32, 2019). Moreover, that in three dimensions can be obtained from the result of Coles and Gustafson (Publ. Res. Inst. Math. Sci. 56:647–699, 2020). On the other hand, the uniqueness in four dimensions has not been completely revealed. The aim in this paper is to prove the uniqueness in three and four dimensions in a unified way. Thus, we obtain a complete answer to the uniqueness problem for ground states at high frequencies. From the point of view of limiting profile of ground states at infinite frequency which is known to be the Aubin–Talenti function, the uniqueness problem in three and four dimensions is more difficult than that in higher dimensions. In this paper, we employ the fixed-point argument developed in Coles and Gustafson (Publ. Res. Inst. Math. Sci. 56:647–699, 2020). Since the application of the argument of Coles and Gustafson (Publ. Res. Inst. Math. Sci. 56:647–699, 2020) to four dimensions is by no means straightforward, we need to construct some estimates for the perturbed resolvents which fit the fixed-point argument (see Proposition
1.2
and (
1.17
)).
In this paper, we prove the global well posedness and the decay estimates for a
Q
-tensor model of nematic liquid crystals in
R
N
,
N
≥
3
. This system is a coupled system by the Navier–Stokes ...equations with a parabolic-type equation describing the evolution of the director fields
Q
. The proof is based on the maximal
L
p
–
L
q
regularity and the
L
p
–
L
q
decay estimates to the linearized problem.
Long-term treatment of Parkinson's disease (PD) by levodopa leads to motor complication "wearing-off". Zonisamide is a nondopaminergic antiparkinsonian drug that can improve "wearing-off" although ...response to the treatment varies between individuals. To clarify the genetic basis of zonisamide responsiveness, we conducted a genome-wide association study (GWAS) on 200 PD patients from a placebo-controlled clinical trial, including 67 responders whose "off" time decreased ≥1.5 h after 12 weeks of zonisamide treatment and 133 poor responders. We genotyped and evaluated the association between 611,492 single nucleotide polymorphisms (SNPs) and "off" time reduction. We also performed whole-genome imputation, gene- and pathway-based analyses of GWAS data. For promising SNPs, we examined single-tissue expression quantitative trait loci (eQTL) data in the GTEx database. SNP rs16854023 (Mouse double minute 4, MDM4) showed genome-wide significant association with reduced "off" time (P
= 4.85 × 10
). Carriers of responsive genotype showed >7-fold decrease in mean "off" time compared to noncarriers (1.42 h vs 0.19 h; P = 2.71 × 10
). In silico eQTL data indicated that zonisamide sensitivity is associated with higher MDM4 expression. Among the 37 pathways significantly influencing "off" time, calcium and glutamate signaling have also been associated with anti-epileptic effect of zonisamide. MDM4 encodes a negative regulator of p53. The association between improved motor fluctuation and MDM4 upregulation implies that p53 inhibition may prevent dopaminergic neuron loss and consequent motor symptoms. This is the first genome-wide pharmacogenetics study on antiparkinsonian drug. The findings provide a basis for improved management of "wearing-off" in PD by genotype-guided zonisamide treatment.
To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from ...Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 × 10−12) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 × 10−9). We also detected strong associations at SNCA on 4q22 (P = 7.35 × 10−17) and LRRK2 on 12q12 (P = 2.72 × 10−8), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and consequent motor dysfunction. Zonisamide ...(1,2‐benzisoxazole‐3‐methanesulfonamide), which was originally developed as an antiepileptic drug, has been found to have therapeutic benefits for PD. However, the pharmacological mechanisms behind the beneficial actions of zonisamide in PD are not fully understood. Here, we investigated the neuroprotective effects of zonisamide on nigrostriatal dopaminergic neurons of the Engrailed mutant mouse, a genetic model of PD. Chronic administration of zonisamide in Engrailed mutant mice was shown to improve the survival of nigrostriatal dopaminergic neurons compared with that under saline treatment. In addition, dopaminergic terminals in the striatum and the motor function were improved in zonisamide‐treated Engrailed mutant mice to the levels of those in control mice. To clarify the mechanism behind the neuroprotective effects of zonisamide, the contents of neurotrophic factors were determined after chronic administration of zonisamide. Brain‐derived neurotrophic factor content was increased in the striatum and ventral midbrain of the zonisamide‐treated mice compared to saline‐treated mice. These findings imply that zonisamide reduces nigrostriatal dopaminergic cell death through brain‐derived neurotrophic factor signaling and may have similar beneficial effects in human parkinsonian patients as well.
Zonisamide (ZNS), an antiepileptic drug, has therapeutic benefits for Parkinson's disease. Chronic ZNS administration improved the survival of dopaminergic neurons and motor function in a genetic mouse model of Parkinson's disease, and increased brain‐derived neurotrophic factor (BDNF) in the brain. ZNS reduces dopaminergic cell death probably through BDNF signaling and may have similar beneficial effects in human parkinsonian patients.
Zonisamide (ZNS), an antiepileptic drug, has therapeutic benefits for Parkinson's disease. Chronic ZNS administration improved the survival of dopaminergic neurons and motor function in a genetic mouse model of Parkinson's disease, and increased brain‐derived neurotrophic factor (BDNF) in the brain. ZNS reduces dopaminergic cell death probably through BDNF signaling and may have similar beneficial effects in human parkinsonian patients.
Purpose
The aim of this multicenter trial was to generate a
123
IFP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan.
Methods
This study included 510 sets of ...SPECT data from 256 healthy controls (116 men and 140 women; age range, 30–83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom.
Results
The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30–39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70–79 age group.
Conclusions
This study provided a large-scale quantitative database of
123
IFP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.
Resting-state functional connectivity magnetic resonance imaging (rsfcMRI) of rapid eye movement (REM) sleep behavior disorder (RBD) may provide an early biomarker of α-synucleinopathy. However, few ...rsfcMRI studies have examined cognitive networks. To elucidate brain network changes in RBD, we performed rsfcMRI in patients with polysomnography-confirmed RBD and healthy controls (HCs), with a sufficiently large sample size in each group.
We analyzed rsfcMRI data from 50 RBD patients and 70 age-matched HCs. Although RBD patients showed no motor signs, some exhibited autonomic and cognitive problems. Several resting-state functional networks were extracted by group independent component analysis from HCs, including the executive-control (ECN), default-mode (DMN), basal ganglia (BGN), and sensory-motor (SMN) networks. Functional connectivity (FC) was compared between groups using dual regression analysis. In the RBD group, correlation analysis was performed between FC and clinical/cognitive scales.
Patients with RBD showed reduced striatal-prefrontal FC in ECN, consistent with executive dysfunctions. No abnormalities were found in DMN. In the motor networks, we identified reduced midbrain-pallidum FC in BGN and reduced motor and somatosensory cortex FC in SMN.
We found abnormal ECN and normal DMN as a possible hallmark of cognitive dysfunctions in early α-synucleinopathies. We replicated abnormalities in BGN and SMN corresponding to subclinical movement disorder of RBD. RsfcMRI may provide an early biomarker of both cognitive and motor network dysfunctions of α-synucleinopathies.
•RBD patients show decreased connectivity in the executive-cognitive network in fMRI.•Motor-network dysfunctions were re-addressed in a large prodromal PD cohort.•Connectivity between basal ganglia and frontal pole correlates with non-motor symptom.
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