Correction: A biocompatible two-photon absorbing fluorescent mitochondrial probe for deep bioimaging.

Correction for 'A biocompatible two-photon absorbing fluorescent mitochondrial probe for deep bioimaging' by Lingmin Lin , , 2022, DOI: 10.1039/d1tb02040d.

Molecular mechanism of agonism and inverse agonism in ghrelin receptor.

Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin.

A biocompatible two-photon absorbing fluorescent mitochondrial probe for deep bioimaging.

Mitochondria, key organelles which keep in tune with energy demands for eukaryotic cells, are firmly associated with neurological conditions and post-traumatic rehabilitation. fluorescence imaging of mitochondria, especially with deep tissue penetration, would open a window to investigate the actual context of the brain. However, the depth of traditional two-photon mitochondrial fluorescence imaging is still limited due to the poor biological compatibility or low two-photon absorption cross-sections.

Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging.

Though commonly used, metal electrodes are incompatible with brain tissues, often leading to injury and failure to achieve long-term implantation. Here we report a subdural neural interface of hydrogel functioning as an ionic conductor, and elastomer as a dielectric. We demonstrate that it incurs a far less glial reaction and less cerebrovascular destruction than a metal electrode.

Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.

Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-G complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.

Molecular Strategies for Intensity-Dependent Olfactory Processing in .

Various odorants trigger complex animal behaviors across species in both quality- and quantity-dependent manners. However, how the intensity of olfactory input is encoded remains largely unknown. Here we report that isoamyl alcohol (IAA) induces bi-directional currents through a Gα- guanylate cyclase (GC)- cGMP signaling pathway in olfactory neuron amphid wing "C" cell (AWC), while two opposite cGMP signaling pathways are responsible for odor-sensing in olfactory neuron amphid wing "B" cell (AWB): (1) a depolarizing Gα (GPA-3)- phosphodiesterase (PDE) - cGMP pathway which can be activated by low concentrations of isoamyl alcohol (IAA), and (2) a hyperpolarizing Gα (ODR-3)- GC- cGMP pathway sensing high concentrations of IAA.

Mechanosensation: Alpha-7 nAChR transduces sound signals in earless C. elegans.

How do organisms without specialized auditory systems perceive and transduce sound? In this issue of Neuron, Iliff et al. (2021) investigate the functional mechanism of airborne sound sensation in Caenorhabditis elegans and highlight the crucial role of alpha-7 nicotinic acetylcholine receptor subunits in mechanotransduction.

Neuronal intranuclear inclusion disease tremor-dominant subtype: A mimicker of essential tremor.

Background And Purpose: The GGC repeat expansion in the NOTCH2NLC gene has been identified as the genetic cause of neuronal intranuclear inclusion disease (NIID). Recently, this repeat expansion was also reported to be associated with essential tremor (ET). However, some patients with this repeat expansion, initially diagnosed with ET, were eventually diagnosed with NIID.

Variants Associated With Idiopathic Generalized Epilepsies.

The objective of this study is to explore the role of gene in idiopathic generalized epilepsies and the potential underlying mechanism for phenotypic variation. Whole-exome sequencing was performed in a cohort of 88 patients with idiopathic generalized epilepsies. Electro-physiological alterations of the recombinant -methyl-D-aspartate receptors (NMDARs) containing GluN2A mutants were examined using two-electrode voltage-clamp recordings.

Bifidobacterium adolescentis regulates catalase activity and host metabolism and improves healthspan and lifespan in multiple species.

To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans.

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina.

Proopiomelanocortin-positive amacrine cells (POMC ACs) were first discovered in adult mouse retinas in 2010; however, the development of POMC-ACs has not been studied. We bred POMC-EGFP mice to label POMC-positive cells and investigated the development of POMC neurons from embryonic to adult stages. We found that POMC neuron development is mainly divided into three stages: the embryonic stage, the closed-eye stage, and the open-eye stage.

Glutamatergic Neurons in the Caudal Zona Incerta Regulate Parkinsonian Motor Symptoms in Mice.

Parkinson's disease (PD) is the second most common and fastest-growing neurodegenerative disorder. In recent years, it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis. However, little is known about whether and how the caudal zona incerta (ZIc) regulates parkinsonian motor symptoms.

Structures of full-length glycoprotein hormone receptor signalling complexes.

Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone. Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs. They activate the same G-protein-coupled receptor, luteinizing hormone-choriogonadotropin receptor (LHCGR), by binding to the large extracellular domain.

Targeting long-term depression of excitatory synaptic transmission for the treatment of neuropathic pain.

Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the somatosensory information from the peripheral to the central nervous system. Long-term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity.

Increasing astrogenesis in the developing hippocampus induces autistic-like behavior in mice via enhancing inhibitory synaptic transmission.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD.

Protocol for targeting the magnocellular neuroendocrine cell ensemble via retrograde tracing from the posterior pituitary.

The hypothalamic magnocellular neuroendocrine cells (MNCs) project to the posterior pituitary (PPi), regulating reproduction and fluid homeostasis. It has been challenging to selectively label and manipulate MNCs, as they are intermingled with parvocellular neuroendocrine cells projecting to the median eminence. Here, we provide a step-by-step protocol for specifically targeting the MNCs by infusing retrograde viral tracers into the PPi.

Excitation-transcription coupling via synapto-nuclear signaling triggers autophagy for synaptic turnover and long-lasting synaptic depression.

For network rewiring and information storage in the brain, late phase long-term synaptic depression (L-LTD) requires the long-lasting reorganization of cellular resources. We found that activation of GRIN/NMDAR recruits transcription-dependent autophagy for synaptic turnover to support L-LTD. Activity-dependent CRTC1 synapto-nuclear translocation increases nuclear CRTC1 that competes with FXR for binding to CREB; this in turn enhances the direct binding between CRTC1-CREB and macroautophagy/autophagy gene promoters.

Structural insights into ligand recognition and activation of the melanocortin-4 receptor.

Melanocortin-4 receptor (MC4R) plays a central role in the regulation of energy homeostasis. Its high sequence similarity to other MC receptor family members, low agonist selectivity and the lack of structural information concerning MC4R-specific activation have hampered the development of MC4R-seletive therapeutics to treat obesity. Here, we report four high-resolution structures of full-length MC4R in complex with the heterotrimeric G protein stimulated by the endogenous peptide ligand α-MSH, FDA-approved drugs afamelanotide (Scenesse™) and bremelanotide (Vyleesi™), and a selective small-molecule ligand THIQ, respectively.

Disrupting phosphorylation of Tyr-1070 at GluN2B selectively produces resilience to depression-like behaviors.

Drugs targeting N-methyl-D-aspartate receptors (NMDARs) have been approved to treat major depressive disorder (MDD); however, the presence of undesirable psychotomimetic and cognitive side effects may limit their utility. In this study, we show that the phosphorylation levels of the GluN2B subunit at tyrosine (Y) 1070 increase in mice after both acute and chronic restraint stress (CRS) exposure. Preventing GluN2B-Y1070 phosphorylation via Y1070F mutation knockin produces effects similar to those of antidepressants but does not affect cognitive or anxiety-related behaviors in subject mice.

Mechanistic insight into high-fat diet-induced metabolic inflammation in the arcuate nucleus of the hypothalamus.

A high-fat diet (HFD) is linked with cytokines production by non-neuronal cells within the hypothalamus, which mediates metabolic inflammation. These cytokines then activate different inflammatory mediators in the arcuate nucleus of the hypothalamus (ARC), a primary hypothalamic area accommodating proopiomelanocortin (POMC) and agouti-related peptide (AGRP) neurons, first-order neurons that sense and integrate peripheral metabolic signals and then respond accordingly. These mediators, such as inhibitor of κB kinase-β (IKKβ), suppression of cytokine signaling 3 (SOCS3), c-Jun N-terminal kinases (JNKs), protein kinase C (PKC), etc.

[Homocysteine and markers of endothelial dysfunction in multiple sclerosis].

Objective: To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis.

Material And Methods: Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received.

[The possibility of using multiple sclerosis-associated variants of the mitochondrial genome to predict the development of multiple sclerosis].

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by autoimmune inflammation, demyelination, and neurodegeneration. MS is a complex disease that develops under the influence of environmental factors in genetically predisposed individuals. Currently, more than 200 genetic loci associated with MS have been identified by various methods.