Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.

Objective: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response.

Methods: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases.

Selective removal of misfolded SOD1 delays disease onset in a mouse model of amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. There is no cure currently. The discovery that mutations in the gene SOD1 are a cause of ALS marks a breakthrough in the search for effective treatments for ALS.

scGCC: Graph Contrastive Clustering With Neighborhood Augmentations for scRNA-Seq Data Analysis.

Single-cell RNA sequencing (scRNA-seq) has rapidly emerged as a powerful technique for analyzing cellular heterogeneity at the individual cell level. In the analysis of scRNA-seq data, cell clustering is a critical step in downstream analysis, as it enables the identification of cell types and the discovery of novel cell subtypes. However, the characteristics of scRNA-seq data, such as high dimensionality and sparsity, dropout events and batch effects, present significant computational challenges for clustering analysis.

Inhibiting NLRP3 inflammasome signaling pathway promotes neurological recovery following hypoxic-ischemic brain damage by increasing p97-mediated surface GluA1-containing AMPA receptors.

Background: The nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is believed to be a key mediator of neuroinflammation and subsequent secondary brain injury induced by ischemic stroke. However, the role and underlying mechanism of the NLRP3 inflammasome in neonates with hypoxic-ischemic encephalopathy (HIE) are still unclear.

Methods: The protein expressions of the NLRP3 inflammasome including NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1) and interleukin-1β (IL-1β), the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor (AMPAR) subunit, and the ATPase valosin-containing protein (VCP/p97), were determined by Western blotting.

GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.

Glutamate N-methyl-D-aspartate receptor (NMDAR) is critical for promoting physiological synaptic plasticity and neuronal viability. As a major subpopulation of the NMDAR, the GluN2B subunit-containing NMDARs have distinct pharmacological properties, physiological functions, and pathological relevance to neurological diseases compared with other NMDAR subtypes. In mature neurons, GluN2B-containing NMDARs are likely expressed as both diheteromeric and triheteromeric receptors, though the functional importance of each subpopulation has yet to be disentangled.

Isomerization of bioactive acylhydrazones triggered by light or thiols.

The acylhydrazone unit is well represented in screening databases used to find ligands for biological targets, and numerous bioactive acylhydrazones have been reported. However, potential E/Z isomerization of the C=N bond in these compounds is rarely examined when bioactivity is assayed. Here we analysed two ortho-hydroxylated acylhydrazones discovered in a virtual drug screen for modulators of N-methyl-D-aspartate receptors and other bioactive hydroxylated acylhydrazones with structurally defined targets reported in the Protein Data Bank.

Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.

ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2.

Potential circRNA-Disease Association Prediction Using DeepWalk and Nonnegative Matrix Factorization.

Circular RNAs (circRNAs) are a category of noncoding RNAs that exist in great numbers in eukaryotes. They have recently been discovered to be crucial in the growth of tumors. Therefore, it is important to explore the association of circRNAs with disease.

Timely insertion of AMPA receptor in developing vestibular circuits is required for manifestation of righting reflexes and effective navigation.

Vestibular information processed first by the brainstem vestibular nucleus (VN), and further by cerebellum and thalamus, underlies diverse brain function. These include the righting reflexes and spatial cognitive behaviour. While the cerebellar and thalamic circuits that decode vestibular information are known, the importance of VN neurons and the temporal requirements for their maturation that allow developmental consolidation of the aforementioned circuits remains unclear.

Allosteric potentiation of GABA receptor single-channel conductance by netrin-1 during neuronal-excitation-induced inhibitory synaptic homeostasis.

As the principal receptor that mediates both synaptic and tonic inhibition of neurons in the brain, the A-type gamma-aminobutyric acid receptor (GABAR) is functionally important for maintaining the balance between neuronal excitation and inhibition. Here, we report the identification of netrin-1 as an endogenous allosteric modulator of GABARs. Following increased neuronal excitability, netrin-1 is secreted and binds to the extracellular domains of GABAR subunits, thereby inducing homeostatic upscaling of GABAR-mediated synaptic efficacy and currents.

Postsynaptic signaling at glutamatergic synapses as therapeutic targets.

Dysregulation of glutamatergic synapses plays an important role in the pathogenesis of neurological diseases. In addition to mediating excitatory synaptic transmission, postsynaptic glutamate receptors interact with various membrane and intracellular proteins. They form structural and/or signaling synaptic protein complexes and thereby play diverse postsynaptic functions.

Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits.

LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role in the molecular organization of synapses in vivo, we studied synapse development and plasticity in hippocampal neuronal circuits in mice lacking both and . We found that LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses on CA1 pyramidal neurons in the developing brain but are not essential for these roles in the mature circuit.

Distinct Functional Alterations and Therapeutic Options of Two Pathological De Novo Variants of the T292 Residue of GABRA1 Identified in Children with Epileptic Encephalopathy and Neurodevelopmental Disorders.

Mutations of GABAR have reportedly led to epileptic encephalopathy and neurodevelopmental disorders. We have identified a novel de novo T292S missense variant of GABRA1 from a pediatric patient with grievous global developmental delay but without obvious epileptic activity. This mutation coincidentally occurs at the same residue as that of a previously reported GABRA1 variant T292I identified from a pediatric patient with severe epilepsy.

The selective dopamine D receptor agonist SKF81297 modulates NMDA receptor currents independently of D receptors.

Dopamine D receptor (DR) agonists are frequently used to study the role of DRs in neurotransmission and behaviour. They have been repeatedly shown to modulate glutamatergic NMDAR currents in the prefrontal cortex (PFC), giving rise to the idea that DR activation tunes glutamatergic networks by regulating NMDAR activity. We report that the widely used DR agonist SKF81297 potentiates NMDAR currents in a dose-dependent manner, independently of DR activation in mPFC slices, cortical neuron cultures and NMDAR-expressing recombinant HEK293 cells.

Convolution Neural Networks Using Deep Matrix Factorization for Predicting Circrna-Disease Association.

CircRNAs have a stable structure, which gives them a higher tolerance to nucleases. Therefore, the properties of circular RNAs are beneficial in disease diagnosis. However, there are few known associations between circRNAs and disease.

GCAEMDA: Predicting miRNA-disease associations via graph convolutional autoencoder.

microRNAs (miRNAs) are small non-coding RNAs related to a number of complicated biological processes. A growing body of studies have suggested that miRNAs are closely associated with many human diseases. It is meaningful to consider disease-related miRNAs as potential biomarkers, which could greatly contribute to understanding the mechanisms of complex diseases and benefit the prevention, detection, diagnosis and treatment of extraordinary diseases.

Predicting miRNA-Disease Association Based on Improved Graph Regression.

Recently, as a growing number of associations between microRNAs (miRNAs) and diseases are discovered, researchers gradually realize that miRNAs are closely related to several complicated biological processes and human diseases. Hence, it is especially important to construct availably models to infer associations between miRNAs and diseases. In this study, we presented Improved Graph Regression for miRNA-Disease Association Prediction (IGRMDA) to observe potential relationship between miRNAs and diseases.

ILPMDA: Predicting miRNA-Disease Association Based on Improved Label Propagation.

MicroRNAs (miRNAs) are small non-coding RNAs that have been demonstrated to be related to numerous complex human diseases. Considerable studies have suggested that miRNAs affect many complicated bioprocesses. Hence, the investigation of disease-related miRNAs by utilizing computational methods is warranted.

WVMDA: Predicting miRNA-Disease Association Based on Weighted Voting.

An increasing number of experiments had verified that miRNA expression is related to human diseases. The miRNA expression profile may be an indicator of clinical diagnosis and provides a new direction for the prevention and treatment of complex diseases. In this work, we present a weighted voting-based model for predicting miRNA-disease association (WVMDA).

21st century excitatory amino acid research: A Q & A with Jeff Watkins and Dick Evans.

In 1981 Jeff Watkins and Dick Evans wrote what was to become a seminal review on excitatory amino acids (EAAs) and their receptors (Watkins and Evans, 1981). Bringing together various lines of evidence dating back over several decades on: the distribution in the nervous system of putative amino acid neurotransmitters; enzymes involved in their production and metabolism; the uptake and release of amino acids; binding of EAAs to membranes; the pharmacological action of endogenous excitatory amino acids and their synthetic analogues, and notably the actions of antagonists for the excitations caused by both nerve stimulation and exogenous agonists, often using pharmacological tools developed by Jeff and his colleagues, they provided a compelling account for EAAs, especially l-glutamate, as a bona fide neurotransmitter in the nervous system. The rest, as they say, is history, but far from being consigned to history, EAA research is in rude health well into the 21st Century as this series of Special Issues of Neuropharmacology exemplifies.

GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases.

Synaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of ionotropic glutamate receptors (AMPARs) mediate the majority of the fast excitatory synaptic transmission in the mammalian brain.