Georgewang5099

Neuronal nicotinic acetylcholine receptors (nAChRs) are prototypical cation-selective, ligand-gated ion channels that mediate fast neurotransmission in the central and peripheral nervous systems. nAChRs are involved in a range of physiological and pathological functions and hence are important therapeutic targets. Their subunit homology and diverse pentameric assembly contribute to their challenging pharmacology and limit their drug development potential. Toxins produced by an extensive range of algae, plants and animals target nAChRs, with many proving pivotal in elucidating receptor pharmacology and biochemistry, as well as providing templates for structure-based drug design. The crystal structures of these toxins with diverse chemical profiles in complex with acetylcholine binding protein (AChBP), a soluble homolog of the extracellular ligand-binding domain of the nAChRs and more recently the extracellular domain of human α9 nAChRs, have been reported. These studies have shed light on the diverse molecular mechanisms of ligand-binding at neuronal nAChR subtypes and uncovered critical insights useful for rational drug design. This review provides a comprehensive overview and perspectives obtained from structure and function studies of diverse plant and animal toxins and their associated inhibitory mechanisms at neuronal nAChRs.This paper attempts to explain some methodological issues regarding EEG signal analysis which might lead to misinterpretation and therefore to unsubstantiated conclusions. The so called "split-alpha," a "new phenomenon" in EEG spectral analysis described lately in few papers is such a case. We have shown that spectrum feature presented as a "split alpha" can be the result of applying improper means of analysis of the spectrum of the EEG signal that did not take into account the significant properties of the applied Fast Fourier Transform (FFT) method. Analysis of the shortcomings of the FFT method applied to EEG signal such as limited duration of analyzed signal, dependence of frequency resolution on time window duration, influence of window duration and shape, overlapping and spectral leakage was performed. Our analyses of EEG data as well as simulations indicate that double alpha spectra called as "split alpha" can appear, as spurious peaks, for short signal window when the EEG signal being studied shows multiple frequencies and frequency bands. These peaks have no relation to any frequencies of the signal and are an effect of spectrum leakage. Our paper is intended to explain the reasons underlying a spectrum pattern called as a "split alpha" and give some practical indications for using spectral analysis of EEG signal that might be useful for readers and allow to avoid EEG spectrum misinterpretation in further studies and publications as well as in clinical practice.A robust association between reduced visual acuity and cognitive function in older adults has been revealed in large population studies. The aim of this work was to assess the relation between stereoacuity, a key aspect of binocular vision, and inhibitory control, an important component of executive functions. Inhibition was tested using the antisaccade task in older adults with normal or reduced stereopsis (study 1), and in young adults with transiently reduced stereopsis (study 2). Older adults with reduced stereopsis made significantly more errors on the antisaccade task in comparison to those with normal stereopsis. Specifically, there was a significant correlation between stereoacuity and antisaccade errors (r = 0.27, p = 0.019). In contrast, there were no significant differences in antisaccade errors between the normal and reduced stereopsis conditions in the young group. Altogether, results suggest that the association between poorer stereopsis and lower inhibitory control in older adults might arise due to central nervous system impairment that affects the processing of binocular disparity and antisaccades. These results add to a growing body of literature, which highlights the interdependence of sensory and cognitive decline in older adults.Glioblastoma (GBM) is the most frequent and aggressive primary central nervous system tumor. Surgery followed by radiotherapy and chemotherapy with alkylating agents constitutes standard first-line treatment of GBM. Complete resection of the GBM tumors is generally not possible given its high invasive features. Although this combination therapy can prolong survival, the prognosis is still poor due to several factors including chemoresistance. In recent years, a comprehensive characterization of the GBM-associated molecular signature has been performed. This has allowed the possibility to introduce a more personalized therapeutic approach for GBM, in which novel targeted therapies, including those employing tyrosine kinase inhibitors (TKIs), could be employed. The GBM tumor microenvironment (TME) exerts a key role in GBM tumor progression, in particular by providing an immunosuppressive state with low numbers of tumor-infiltrating lymphocytes (TILs) and other immune effector cell types that contributes to tumor proliferation and growth. The use of immune checkpoint inhibitors (ICIs) has been successfully introduced in numerous advanced cancers as well as promising results have been shown for the use of these antibodies in untreated brain metastases from melanoma and from non-small cell lung carcinoma (NSCLC). Consequently, the use of PD-1/PD-L1 inhibitors has also been proposed in several clinical trials for the treatment of GBM. In the present review, we will outline the main GBM molecular and TME aspects providing also the grounds for novel targeted therapies and immunotherapies using ICIs for GBM.Recent clinical trials failed to endorse dichoptic training for amblyopia treatment. Here, we proposed an alternative training strategy that focused on reducing signal threshold contrast in the amblyopic eye under a constant and high noise contrast in the fellow eye (HNC), and compared it to a typical dichoptic strategy that aimed at increasing the tolerable noise contrast in the fellow eye (i.e., TNC strategy). We recruited 16 patients with amblyopia and divided them into two groups. Eight patients in Group 1 received the HNC training, while the other eight patients in Group 2 performed the TNC training first (Phase 1) and then crossed over to the HNC training (Phase 2). We measured contrast sensitivity functions (CSFs) separately in the amblyopic and fellow eyes when the untested eye viewed mean luminance (monocularly unmasked) or noise stimuli (dichoptically masked) before and after training at a particular frequency. The area under the log contrast sensitivity function (AULCSF) of masked and unmasked conditions, and dichoptic gain (the ratio of AULCSF of masked to unmasked condition) were calculated for each eye. We found that both dichoptic training paradigms substantially improved masked CSF, dichoptic gain, and visual acuity in the amblyopic eye. As opposed to the TNC paradigm, the HNC training produced stronger effects on masked CSFs, stereoacuity, dichoptic gain, and visual acuity in the amblyopic eye. Interestingly, the second-phase HNC training in Group 2 also induced further improvement in the masked contrast sensitivity and AULCSF in the amblyopic eye. We concluded that the HNC training strategy was more effective than the TNC training paradigm. Future design for dichoptic training should not only focus on increasing the tolerable noise contrast in the fellow eye but should also "nurture" the amblyopic eye under normal binocular viewing conditions and sustained interocular suppression.The combination of neuromorphic visual sensors and spiking neural network offers a high efficient bio-inspired solution to real-world applications. However, processing event- based sequences remains challenging because of the nature of their asynchronism and sparsity behavior. In this paper, a novel spiking convolutional recurrent neural network (SCRNN) architecture that takes advantage of both convolution operation and recurrent connectivity to maintain the spatial and temporal relations from event-based sequence data are presented. The use of recurrent architecture enables the network to have a sampling window with an arbitrary length, allowing the network to exploit temporal correlations between event collections. Rather than standard ANN to SNN conversion techniques, the network utilizes a supervised Spike Layer Error Reassignment (SLAYER) training mechanism that allows the network to adapt to neuromorphic (event-based) data directly. The network structure is validated on the DVS gesture dataset and achieves a 10 class gesture recognition accuracy of 96.59% and an 11 class gesture recognition accuracy of 90.28%.Background Cerebral palsy (CP) is a syndrome of non-progressive motor dysfunction caused by early brain development injury. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP. Methods We recruited 782 children with CP as the case group and 770 healthy children as the control group. see more The association between IL-23R single nucleotide polymorphisms (SNPs; namely, rs10889657, rs6682925, rs1884444, rs17375018, rs1004819, rs11805303, and rs10889677) and CP was studied by using a case-control method and SHEsis online software. Subgroup analysis based on complications and clinical subtypes was also carried out. Results There were differences in the allele and genotype frequencies between CP cases and controls at the rs11805303 and rs10889677 SNPs (Pallele = 0.014 and 0.048, respectively; Pgenotype = 0.023 and 0.008, respectively), and the difference in genotype frequency of rs10889677 remained significant after Bonferroni correction (Pgenotype = 0.048). Subgroup analysis revealed a more significant association of rs10889677 with CP accompanied by global developmental delay (Pgenotype = 0.024 after correction) and neonatal encephalopathy (Pgenotype = 0.024 after correction). Conclusion The present results showed a significant association between IL-23R and CP, suggesting that IL-23R may play a potential role in CP pathogenesis.Background The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear. Objective This meta-analysis aimed to examine the associations between OI and Aβ and tau burden. Methods Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aβ or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups. Results Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aβ PET, one involved tau PET (N = 26), and four involved CSF Aβ or tau (N = 345). OI was negatively associated with Aβ PET in the mixed (r = -0.25, P = 0.008) and cognitively normal groups (r = -0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aβ42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET. Conclusion The associations between OI ability and Aβ and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.