In this paper, we introduce the “coupled Ricci iteration”, a dynamical system related to the Ricci operator and twisted Kähler–Einstein metrics as an approach to the study of coupled Kähler–Einstein ...(CKE) metrics. For negative 1st Chern class, we prove the smooth convergence of the iteration. For positive 1st Chern class, we also provide a notion of coercivity of the Ding functional and show its equivalence to the existence of CKE metrics. As an application, we prove the smooth convergence of the iteration on CKE Fano manifolds assuming that the automorphism group is discrete.
We study the line bundle mean curvature flow on Kähler surfaces under the hypercritical phase and a certain semipositivity condition. We naturally encounter such a condition when considering the ...blowup of Kähler surfaces. We show that the flow converges smoothly to a singular solution to the deformed Hermitian–Yang–Mills equation away from a finite number of curves of negative self-intersection on the surface. As an application, we obtain a lower bound of a Kempf–Ness type functional on the space of potential functions satisfying the hypercritical phase condition.
Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's ...disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc.
We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology.
The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model.
These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.
Parkinson’s disease is a neurodegenerative disorder that involves movement discloses, degeneration of dopaminergic neurons, and presence of cytoplasmic inclusion bodies. Various animal models have ...been developed and small fish including zebrafish and medaka fish have recently been employed as a new model for Parkinson disease. In this review, we summarize fish models of Parkinson’s disease mainly using our own findings and explain two major hypotheses of PD: lysosome dysfunction theory and mitochondrial dysfunction theory. Finally, we discuss the potential for future application of small fish model.
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. Foxp3
regulatory T (Treg) cells are reduced in frequency and dysfunctional in patients with MS, but the ...underlying mechanisms of this deficiency are unclear. Here, we show that induction of human IFN-γ
IL-17A
Foxp3
CD4
T cells is inhibited in the presence of circulating exosomes from patients with MS. The exosomal miRNA profile of patients with MS differs from that of healthy controls, and let-7i, which is markedly increased in patients with MS, suppresses induction of Treg cells by targeting insulin like growth factor 1 receptor (IGF1R) and transforming growth factor beta receptor 1 (TGFBR1). Consistently, the expression of IGF1R and TGFBR1 on circulating naive CD4
T cells is reduced in patients with MS. Thus, our study shows that exosomal let-7i regulates MS pathogenesis by blocking the IGF1R/TGFBR1 pathway.
•Cerebral hypoperfusion may induce upregulation of NLRP3, AIM2-inflammasomes.•NLRP3 could have a role in the sterile inflammatory responses in astrocytes, and AIM2 in microglia cells.•IL-1β and IL-18 ...were upregulated in BCAS mice, together with increased expression of the inflammasome.•NLRP3, AIM2-inflammasomes may correlate with neuroinflammation in chronic cerebral ischemia.
Inflammation plays an important role in acute and chronic cerebral ischemia. Recent reports indicate that the inflammatory response triggered by tissue damage is mediated by a multiple-protein complex called the inflammasome. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasome complex triggers caspase 1-mediated maturation of interleukin (IL)-1β and IL-18. This study tested the hypothesis that chronic cerebral hypoperfusion activates inflammasomes in the white matter of the brain. To induce cerebral hypoperfusion, C57BL/6J mice were subjected to a sham or bilateral common carotid artery stenosis (BCAS) operation using microcoils with an internal diameter of 0.18 mm. At 2 and 4 weeks after BCAS, the mice were sacrificed (n = 5 in each group). Coronal sections were stained with anti-NLRP3 and anti-AIM2 antibodies. Activation of the inflammasome and cytokines was assessed using immunohistochemistry and cell counting. IL-18 and IL-1β levels were determined by ELISA. Cell counting revealed an increase in NLRP3 and AIM2 inflammasomes at 2 and 4 weeks after BCAS. Immunoreactivity was observed in glial cells in the white matter and corpus callosum. IL-18 and IL-1β concentrations were significantly increased compared with those in the sham operation group. Expression of NLRP3 and AIM2 was upregulated in glial cells in the autopsied brains of patients with cerebral infarction in the chronic phase. These results suggest that chronic cerebral hypoperfusion induces upregulation of NLRP3 and AIM2 inflammasomes; therefore, inflammasomes may play an important role in the sterile inflammatory response in astrocytes and microglia during chronic cerebral hypoperfusion.
This study aimed to evaluate the efficacy of preemptive middle glenohumeral ligament (MGHL) release in arthroscopic rotator cuff repair (ARCR) to reduce postoperative stiffness.
Patients who ...underwent ARCR were enrolled and allocated into two groups retrospectively: the preemptive MGHL release group (n = 44) and the preemptive MGHL non-release group (n = 42). Clinical outcomes were assessed and compared between the two groups, including the range of motion, Japanese Orthopedic Association Shoulder Score, Constant Shoulder Score, and the University of California, Los Angeles Score preoperatively and 3 months, 6 months, and 12 months postoperatively and complications. The integrity of the repaired tendon was assessed at the 12-month follow-up using magnetic resonance imaging.
There were no significant differences between the groups in all range of motion and all functional scores at any of the assessed time points. There was also no significant difference in the healing failure rate 2.3% in the preemptive MGHL group and 2.4% in the preemptive MGHL non-release group (p = .97), and postoperative stiffness was 2.3% in the preemptive MGHL group and 7.1% in the preemptive MGHL non-release group (p = .28). There was no postoperative instability in both group.
ARCR effectively facilitates the recovery of range of motion and function in patients with a rotator cuff tear. However, preemptive MGHL release could not be an effective method to reduce postoperative stiffness.
A new type of thiadiazole-based acceptor unit and its donor–acceptor copolymers were synthesized and characterized to develop the high-performance semiconducting polymers for organic field-effect ...transistors (OFETs) and organic photovoltaics (OPVs). We successfully synthesized an anthra1,2-c:5,6-c′bis(1,2,5thiadiazole) (ATz) core and ATz-quaterthiophene copolymers. These copolymers possess a wide energy gap of ca. 1.8 eV and a deeper HOMO energy levels around −5.4 eV than that of typical thiadiazole–oligothiophene copolymers. Such weak electron-accepting nature may be due to the decreased electron affinity of the ATz core by an existence of alkoxy groups with strong electron-donating ability. The ATz copolymers exhibited good semiconducting properties with hole mobility of up to 0.03 cm2 V–1 s–1 and photovoltaic response with PCE of up to 5.7%, despite the unfavorable molecular orders, thin-film structure, and/or amorphous structure.
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