Mcphersonchristoffersen0796

Decreased expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is implicated in the pathophysiology of Parkinson's disease (PD). However, our understanding of the mechanism regulating the PGC-1α expression is still limited. We sought to determine whether the epigenetic modification of PPARGC1A (the gene encoding PGC-1α) could account for its diminished expression. We performed a study of PPARGC1A risk-SNP genotypes, methylation level, and the expression in blood from 171 subjects. The mean DNA methylation level of PPARGC1A intron 1 in patients with PD was higher than that in the controls (7.18 ± 1.74 vs. 6.36 ± 1.28, P = 0.007). A detailed comparison of the DNA methylation level at each CpG site showed that CpG_1, CpG_13.14, CpG_17.18, and CpG_20 were significantly hypermethylated in patients with PD. There was a significant negative correlation between PPARGC1A methylation and expression level (R = -0.404, P less then 0.001). We found no correlations between the PPARGC1A methylation level and the clinical features, while the CpG_13.14 site methylation level was positively correlated with H&Y stage (R = 0.246, P = 0.020) and was increased in people carrying the rs2970848 AA genotype compared with that in carriers of the AG/GG genotype (7.27 ± 1.86 vs. 6.65 ± 1.92, P = 0.032). Our results support a link between PPARGC1A methylation, gene expression, and variability, which indicated that a novel epigenetic regulatory mechanism controlling PPARGC1A expression influences PD pathogenesis. Copyright © 2020 Yang, Xu, Qian, He, Chen and Xiao.The development of highly integrated electrophysiological devices working in direct contact with living neuron tissue opens new exciting prospects in the fields of neurophysiology and medicine, but imposes tight requirements on the power dissipated by electronics. Tween 80 On-chip preprocessing of neuronal signals can substantially decrease the power dissipated by external data interfaces, and the addition of embedded non-volatile memory would significantly improve the performance of a co-processor in real-time processing of the incoming information stream from the neuron tissue. Here, we evaluate the parameters of TaO x -based resistive switching (RS) memory devices produced by magnetron sputtering technique and integrated with the 180-nm CMOS field-effect transistors as possible candidates for on-chip memory in the hybrid neurointerface under development. The electrical parameters of the optimized one-transistor-one-resistor (1T-1R) devices, such as the switching voltage (approx. ±1 V), uniformity of the R off/R on ratio (∼10), read/write speed ( less then 40 ns), and the number of the writing cycles (up to 1010), are satisfactory. The energy values for writing and reading out a bit ∼30 and ∼0.1 pJ, respectively, are also suitable for the desired in vitro neurointerfaces, but are still far too high once the prospective in vivo applications are considered. Challenges arising in the course of the prospective fabrication of the proposed TaO x -based RS devices in the back-end-of-line process are identified. Copyright © 2020 Zhuk, Zarubin, Karateev, Matveyev, Gornev, Krasnikov, Negrov and Zenkevich.Development of spiking neural networks (SNNs) controlling mobile robots is one of the modern challenges in computational neuroscience and artificial intelligence. Such networks, being replicas of biological ones, are expected to have a higher computational potential than traditional artificial neural networks (ANNs). The critical problem is in the design of robust learning algorithms aimed at building a "living computer" based on SNNs. Here, we propose a simple SNN equipped with a Hebbian rule in the form of spike-timing-dependent plasticity (STDP). The SNN implements associative learning by exploiting the spatial properties of STDP. We show that a LEGO robot controlled by the SNN can exhibit classical and operant conditioning. Competition of spike-conducting pathways in the SNN plays a fundamental role in establishing associations of neural connections. It replaces the irrelevant associations by new ones in response to a change in stimuli. Thus, the robot gets the ability to relearn when the environment changes. The proposed SNN and the stimulation protocol can be further enhanced and tested in developing neuronal cultures, and also admit the use of memristive devices for hardware implementation. Copyright © 2020 Lobov, Mikhaylov, Shamshin, Makarov and Kazantsev.Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clght © 2020 Zawilska, Kacela and Adamowicz.Background The astrocytic phospholipase A2 (PLA2)-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer's disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive. Objective To investigate the effect of MA on the astrocytic PLA2-AA pathway in SAMP8 mice hippocampi. Methods SAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 μg/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory.