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In this phase 3 trial, among infants with spinal muscular atrophy, those who received nusinersen were more likely to achieve major motor milestones and less likely to need permanent assisted ventilation than those who underwent a sham procedure.

[This corrects the article DOI: 10.1371/journal.pcbi.1007074.].

[This corrects the article DOI: 10.1371/journal.pone.0278343.].

[This corrects the article DOI: 10.1371/journal.pgen.1004747.].[This corrects the article DOI: 10.1371/journal.pgen.1004747.].

One of the hallmarks of Parkinson’s disease (PD) is the alteration in the expression and function of NMDA receptor (NMDAR) and cannabinoid receptor 1 (CB[sub.1]R). The presence of CB[sub.1]R-NMDAR complexes has been described in neuronal primary cultures. The activation of CB[sub.1]R in CB[sub.1]R-NMDAR complexes was suggested to counteract the detrimental NMDAR overactivation in an AD mice model. Thus, we aimed to explore the role of this receptor complex in PD. By using Bioluminescence Resonance Energy Transfer (BRET) assay, it was demonstrated that α-synuclein induces a reorganization of the CB[sub.1]R-NMDAR complex in transfected HEK-293T cells. Moreover, α-synuclein treatment induced a decrease in the cAMP and MAP kinase (MAPK) signaling of both CB[sub.1]R and NMDAR not only in transfected cells but also in neuronal primary cultures. Finally, the interaction between CB[sub.1]R and NMDAR was studied by Proximity Ligation Assay (PLA) in neuronal primary cultures, where it was observed that the expression of CB[sub.1]R-NMDAR complexes was decreased upon α-synuclein treatment. These results point to a role of CB[sub.1]R-NMDAR complexes as a new therapeutic target in Parkinson’s disease.

Metal-organic gels (MOGs) are unique supramolecular gels that are convenient to synthesize. In this work, a cathodic electrochemiluminescence (ECL) system based on Ag-MOGs as a luminophore and K.sub.2S.sub.2O.sub.8 as a co-reactor was developed. The ECL spectrum of the Ag-MOGs overlapped significantly with the strong UV-Vis spectrum of the SiO.sub.2@PANI@AuNPs, which effectively quenched the ECL luminescence of the Ag-MOGs. Relying on the inner filter effect between Ag-MOGs and SiO.sub.2@PANI@AuNPs, a novel ECL-IFE immunosensor was developed for the detection of neuron-specific enolase (NSE). Under optimal conditions, the ECL signal of the immunosensor displayed excellent linearity over the NSE concentration range of 10 fg/mL-100 ng/mL. The limit of detection (LOD) was 2.6 fg/mL (S/N = 3) with a correlation coefficient R.sup.2 of 0.9975. The ECL immunosensor also exhibited excellent stability and reproducibility for the detection of NSE. The results reported provide a feasible concept for the development analytical methods for the detection of other clinically relevant biomarkers. Graphical

Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and [alpha]2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal-to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na.sup.+ leak channel NALCN in mice and found that its presence was required for spontaneous firing in cartwheel cells. Activation of [alpha]2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, [alpha]2-dependent enhancement of synaptic strength was also absent in the knockout. GABA.sub.B receptors mediated inhibition through NALCN as well, acting on the same population of channels as [alpha]2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN.