Ground State Energy of the Polaron in the Relativistic Quantum Electrodynamics

We consider the polaron model in the relativistic quantum electrodynamics( QED). We prove that the ground state energy of the model is finite for all values of the fine-structure constant and the ultraviolet cutoff $\Lambda$. Moreover we give an upper bound and a lower bound of the ground state energy

Comparison and nuclearity of spaces of differential forms on topological vector spaces

Two types of fundamental spaces of differential forms on infinite dimensional topological vector spaces are considered; one is a fundamental space of Hida's type and the other is one of Malliavin's. It is proven that the former space is smaller than the latter. Moreover, it is shown that, under some conditions, the fundamental space of Hida's type is nuclear as a complete countably normed space, while that of Malliavin's in the L2 sense is not

Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse

GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-autho

One-year follow-up for the therapeutic efficacy of pregabalin in patients with leg symptoms caused by lumbar spinal stenosis

AbstractBackground Pregabalin is a well-accepted treatment option for patients with neuropathic pain. However, the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery to treat leg symptoms in patients with lumbar spinal stenosis remains unknown. The purpose of this study was to analyze the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery for leg symptoms in patients with lumbar spinal stenosis during the first year of treatment.Methods Consecutive patients diagnosed with lumbar spinal stenosis at our hospital from January to June 2009 were treated with nonsteroidal anti-inflammatory drug monotherapy and formed the control group (n = 47; 22 males, 25 females). Patients diagnosed with lumbar spinal stenosis at our hospital between August 2010 and October 2011 were treated with a nonsteroidal anti-inflammatory drug and pregabalin combination therapy and formed the pregabalin group (n = 49; 27 males, 22 females). The proportions of patients who underwent spinal surgery during the first year of treatment were assessed and compared between the two groups using the Mann-Whitney U test. In addition, the periods in which patients decided to undergo spinal surgery were compared using the Kaplan-Meier method.Results Six patients (12.2 %) in the pregabalin group and 22 patients (46.8 %) in the control group underwent spinal surgery during the first year of treatment (P = 0.0035). The period in which patients decided to undergo spinal surgery was significantly delayed in the pregabalin group compared with the control group in those for whom spinal surgery was necessary (P = 0.0128).Conclusions Nonsteroidal anti-inflammatory drug and pregabalin combination therapy may result in a lower incidence of spinal surgery during the first year of treatment or a delayed period before undergoing spinal surgery if necessary compared with nonsteroidal anti-inflammatory drug monotherapy in patients with leg symptoms caused by lumbar spinal stenosis

Chemical labelling for visualizing native AMPA receptors in live neurons

The location and number of neurotransmitter receptors are dynamically regulated at postsynaptic sites. However, currently available methods for visualizing receptor trafficking require the introduction of genetically engineered receptors into neurons, which can disrupt the normal functioning and processing of the original receptor. Here we report a powerful method for visualizing native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) which are essential for cognitive functions without any genetic manipulation. This is based on a covalent chemical labelling strategy driven by selective ligand-protein recognition to tether small fluorophores to AMPARs using chemical AMPAR modification (CAM) reagents. The high penetrability of CAM reagents enables visualization of native AMPARs deep in brain tissues without affecting receptor function. Moreover, CAM reagents are used to characterize the diffusion dynamics of endogenous AMPARs in both cultured neurons and hippocampal slices. This method will help clarify the involvement of AMPAR trafficking in various neuropsychiatric and neurodevelopmental disorders

Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains

生きた動物脳内で発現する神経伝達物質受容体に目印を付ける新手法を開発 --遺伝子操作を伴わず、生体内でたんぱく質の機能解析が可能に--. 京都大学プレスリリース. 2024-02-05.Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because the spatiotemporal expression profiles and dynamics of neurotransmitter receptors involved in many functions are delicately governed in the brain, in vivo research tools with high spatiotemporal resolution for receptors in intact brains are highly desirable. Covalent labeling by chemical reaction (chemical labeling) of proteins without genetic manipulation is now a powerful method for analyzing receptors in vitro. However, selective target receptor labeling in the brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes to target endogenous receptors in living mouse brains. The reactive LDAI reagents with negative charges were found to diffuse well over the whole brain and could selectively label target endogenous receptors, including AMPAR, NMDAR, mGlu1, and GABAAR. This simple and robust labeling protocol was then used for various applications: three-dimensional spatial mapping of endogenous receptors in the brains of healthy and disease-model mice; multi-color receptor imaging; and pulse–chase analysis of the receptor dynamics in postnatal mouse brains. Here, results demonstrated that bioorthogonal receptor modification in living animal brains may provide innovative molecular tools that contribute to the in-depth understanding of complicated brain functions

Interfacial fracture strength property of micro-scale SiN/Cu components

AbstractThe strength against fracture nucleation from an interface free-edge of silicon-nitride (SiN)/copper (Cu) micro-components is evaluated. A special technique that combines a nano-indenter specimen holder and an environmental transmission electron microscope (E-TEM) is employed. The critical load at the onset of fracture nucleation from a wedge-shaped free-edge (opening angle: 90°) is measured both in a vacuum and in a hydrogen (H2) environment, and the critical stress distribution is evaluated by the finite element method (FEM). It is found that the fracture nucleation is dominated by the near-edge elastic singular stress field that extends about a few tens of nanometers from the edge. The fracture nucleation strength expressed in terms of the stress intensity factor (K) is found to be eminently reduced in a H2 environment

Structural aging of human neurons is the opposite of the changes in schizophrenia

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 x 10^(-4)). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 x 10^(-4)), indicating that neurite structure is relevant to brain function. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia. This nano-CT paper is the result of our decade-long analysis and is unprecedented in terms of number of cases.Comment: 24 pages, 5 figures. arXiv admin note: text overlap with arXiv:2007.0021