FMR1 mutant marmosets show fragile X syndrome phenotypes.

Fragile X syndrome (FXS) is the foremost monogenic cause of autism spectrum disorder and intellectual disability, caused by FMR1 gene silencing. Here, we report that common marmosets carrying FMR1 mutation, a non-human primate model for FXS, share common features in behavioral and molecular phenotypes with patients with FXS. Founder mutants with markedly reduced fragile X messenger ribonucleoprotein expression display hyperactivity, spontaneous seizures, and transcriptome changes in synapse-related genes that overlap with those reported in patients with FXS.

A comprehensive suite for extracting neuron signals across multiple sessions in one-photon calcium imaging.

We developed CaliAli, a comprehensive suite designed to extract neuronal signals from one-photon calcium imaging data collected across multiple sessions in free-moving conditions in mice. CaliAli incorporates information from blood vessels and neurons to correct inter-session misalignments, making it robust against non-rigid brain deformations even after substantial changes in the field of view across sessions. This also makes CaliAli robust against high neuron overlap and changes in active neuron population across sessions.

Analysis of cell death in Bacillus subtilis caused by sesquiterpenes from Chrysopogon zizanioides (L.) Roberty.

Recently, the antibacterial effects of essential oils have been investigated in addition to their therapeutic purposes. Owing to their hydrophobic nature, they are thought to perturb the integrity of the bacterial cell membrane, leading to cell death. Against such antibiotic challenges, bacteria develop mechanisms for cell envelope stress responses (CESR).

Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex.

Methylglyoxal (MG) is a reactive and cytotoxic α-dicarbonyl byproduct of glycolysis. Our bodies have several bio-defense systems to detoxify MG, including an enzymatic system by glyoxalase (GLO) 1 and GLO2. We identified a subtype of schizophrenia patients with novel mutations in the GLO1 gene that results in reductions of enzymatic activity.

Calcium imaging of adult-born neurons in freely moving mice.

Adult-born neurons (ABNs) in the dentate gyrus bestow unique cellular plasticity to the mammalian brain. We recently found that the activity of ABNs during sleep is necessary for memory consolidation. Here, we describe our method for Ca imaging of ABN activity using a miniaturized fluorescent microscope and sleep recordings.

A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders.

Objective: Neurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large-scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs.

Sparse Activity of Hippocampal Adult-Born Neurons during REM Sleep Is Necessary for Memory Consolidation.

The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown.

Indirect Down-regulation of Tumor-suppressive Family MicroRNAs by in Neuroblastoma.

Background/aim: Overall survival for the high-risk group of neuroblastoma (NB) patients still remains at 40-50%, necessitating the establishment of a curable treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is an NB-susceptibility gene with a tumor-promoting activity. Previously we conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell lines and identified 3 protein-coding genes regulated by LMO1.

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses.

Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma.

Background/aim: Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed.

Materials And Methods: We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines.

Crucial Roles of the Endocannabinoid 2-Arachidonoylglycerol in the Suppression of Epileptic Seizures.

Endocannabinoid signaling is considered to suppress excessive excitability of neural circuits and to protect the brain from seizures. However, the precise mechanisms of this effect are poorly understood. Here, we report that 2-arachidonoylglycerol (2-AG), one of the two major endocannabinoids, is crucial for suppressing seizures.

Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.

Postsynaptic kainate-type glutamate receptors (KARs) regulate synaptic network activity through their slow channel kinetics, most prominently at mossy fiber (MF)-CA3 synapses in the hippocampus. Nevertheless, how KARs cluster and function at these synapses has been unclear. Here, we show that C1q-like proteins C1ql2 and C1ql3, produced by MFs, serve as extracellular organizers to recruit functional postsynaptic KAR complexes to the CA3 pyramidal neurons.

Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders.

Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor.

Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies.

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data.

Selective activation of mTORC1 signaling recapitulates microcephaly, tuberous sclerosis, and neurodegenerative diseases.

Mammalian target of rapamycin (mTOR) has been implicated in human neurological diseases such as tuberous sclerosis complex (TSC), neurodegeneration, and autism. However, little is known about when and how mTOR is involved in the pathogenesis of these diseases, due to a lack of animal models that directly increase mTOR activity. Here, we generated transgenic mice expressing a gain-of-function mutant of mTOR in the forebrain in a temporally controlled manner.

The endocannabinoid 2-arachidonoylglycerol negatively regulates habituation by suppressing excitatory recurrent network activity and reducing long-term potentiation in the dentate gyrus.

Endocannabinoids are known to mediate retrograde suppression of synaptic transmission, modulate synaptic plasticity, and influence learning and memory. The 2-arachidonoylglycerol (2-AG) produced by diacylglycerol lipase α (DGLα) is regarded as the major endocannabinoid that causes retrograde synaptic suppression. To determine how 2-AG signaling influences learning and memory, we subjected DGLα knock-out mice to two learning tasks.

Induction of DNA damage, including abasic sites, in plasmid DNA by carbon ion and X-ray irradiation.

DNA from plasmid pUC18 was irradiated with low-LET (13 keV/μm) or high-LET (60 keV/μm) carbon ions or X-rays (4 keV/μm) in solutions containing several concentrations of Tris (0.66-200 mM) to determine the yield of abasic (AP) sites and the effect of scavenging capacity. The yield of AP sites, detected as single-strand breaks (SSB) after digestion with E.

Vagus nerve stimulation induced long-lasting enhancement of synaptic transmission and decreased granule cell discharge in the hippocampal dentate gyrus of urethane-anesthetized rats.

Vagus nerve stimulation (VNS) ameliorates deficits of hippocampal functions, such as contextual learning and memory, probably through direct modulation of neuronal activity. Previous studies showed that VNS enhanced excitatory synaptic transmission in the hippocampal CA3 area via activation of β-adrenergic receptors. However, effects of VNS on excitatory synaptic transmission and action potential (AP) discharge of granule cells (GCs) in the dentate gyrus have not been studied.

MLEP: an R package for exploring the maximum likelihood estimates of penetrance parameters.

Background: Linkage analysis is a useful tool for detecting genetic variants that regulate a trait of interest, especially genes associated with a given disease. Although penetrance parameters play an important role in determining gene location, they are assigned arbitrary values according to the researcher's intuition or as estimated by the maximum likelihood principle. Several methods exist by which to evaluate the maximum likelihood estimates of penetrance, although not all of these are supported by software packages and some are biased by marker genotype information, even when disease development is due solely to the genotype of a single allele.

NDesign: software for study design for the detection of rare variants from next-generation sequencing data.

We developed a software program, NDesign, for the design of a study intended for detecting rare variants from next-generation sequencing (NGS) data. In this study design, the optimal depth of coverage and the average depth of coverage are first evaluated, and then the ability of the designed experiment to obtain a desired power is determined. NDesign has been developed to calculate both these depths, as well as to evaluate the power of the designed experiment.

Exploration of the disease locus by a careful evaluation of the likelihood polynomial for pedigree data.

It is demonstrated through two case studies that a careful evaluation of the likelihood polynomial results in a more accurate localization of disease locus. The evaluation of the likelihood function as a polynomial enables more flexible exploration of the disease locus. Visualization by a contour plot of the function on a unit square of paternal and maternal recombination fractions along with a superimposed ellipsoid of the Fisher information matrix helps us to find a more accurate localization of the disease locus.