Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNF) in which the conversion of proBDNF to mBDNF is attenuated.

Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in -Ethylmaleimide Sensitive Factor Gene-Deficient Mice.

Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified -ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake .

Simple methods for the lesion detection and severity grading of diabetic retinopathy by image processing and transfer learning.

Diabetic retinopathy (DR) has become one of the major causes of blindness. Due to the increased prevalence of diabetes worldwide, diabetic patients exhibit high probabilities of developing DR. There is a need to develop a labor-less computer-aided diagnosis system to support the clinical diagnosis.

Neuropsin-dependent and -independent behavioral tagging.

Aim: The consolidation of short-term memories into long-term memories is promoted by associations with novel environmental stimuli. This phenomenon is known as behavioral tagging. Neuropsin, a plasticity-related serine protease in the hippocampus and amygdala, is involved in memory formation.

[A PHASE III STUDY TO EVALUATE SAFETY AND EFFICACY OF FLUTICASONE/FORMOTEROL COMBINATION (FLUTIFORM AEROSOL) IN LONG-TERM ADMINISTRATION (24 WEEKS) IN JAPANESE PEDIATRIC PATIENTS WITH BRONCHIAL ASTHMA].

Background: The combination drug of inhaled corticosteroid (ICS)/long-acting β2 agonist is being used as a long-term control medication for pediatric asthma patients for those who are poorly controlled by ICS alone. Long-term efficacy and safety of Fluticasone propionate/formoterol fumarate hydrate (FP/FM) was evaluated in pediatric patients with bronchial asthma.

Methods: Two inhales of FP/FM (50/5μg) at one time, twice daily were administered for 24 weeks to Japanese asthma patients aged 5 to ＜16 years who had asthma symptoms during the observation period while using the same dosage of ICS during a certain period of time.

Prominin-1 Modulates Rho/ROCK-Mediated Membrane Morphology and Calcium-Dependent Intracellular Chloride Flux.

Membrane morphology is an important structural determinant as it reflects cellular functions. The pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to protrusions and plays a pivotal role in migration and the determination of cellular morphology; however, the underlying mechanism of its action have been elusive. Here, we performed molecular characterisation of Prom1, focussing primarily on its effects on cell morphology.

Dataset on the effect of knockout of KLK8 in social memory.

The data presented in this article have been produced as supporting data of the original research article titled "Impaired social discrimination behavior despite normal social approach by kallikrein-related peptidase 8 knockout mouse" (Nakazawa et al., 2019). Sociability and recognition of conspecifics and discrimination among conspecifics (social memory) is fundamental for pair bonding, to create social hierarchy, and eventually establish affiliated societies in social animals, including humans.

Impaired social discrimination behavior despite normal social approach by kallikrein-related peptidase 8 knockout mouse.

For social mammals, recognition of conspecifics and discrimination of each other (social memory) is crucial to living in a stable colony. Here, we investigated whether kallikrein-related peptidase 8 (KLK8)-neuregulin 1 (NRG1)-ErbB signaling is crucial for social discrimination behavior using the social discrimination three chamber behavioral test. Klk8 knockout mice (NRG1-deactivated mice) exhibited normal social approach but impaired social discrimination.

PIP-Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover.

The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP, functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation.

BDNF Binds Its Pro-Peptide with High Affinity and the Common Val66Met Polymorphism Attenuates the Interaction.

Most growth factors are initially synthesized as precursors then cleaved into bioactive mature domains and pro-domains, but the biological roles of pro-domains are poorly understood. In the present study, we investigated the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post-processing product of the precursor BDNF.

Point-to-Point Ultra-Remote Asymmetric Control with Flexible Linker.

An ultra-remote intramolecular (point-to-point) asymmetric control through 38 bonds (1,39-asymmetric induction) has been achieved by using the principle of direct supramolecular orientation of catalytic and reactive moieties in asymmetric autocatalysis. We found the highly stereoselective diisopropylzinc addition reaction using designed molecules possessing pyrimidine sites at each terminal of a conformationally flexible simple methylene chain.

"Optical communication with brain cells by means of an implanted duplex micro-device with optogenetics and Ca(2+) fluoroimaging".

To better understand the brain function based on neural activity, a minimally invasive analysis technology in a freely moving animal is necessary. Such technology would provide new knowledge in neuroscience and contribute to regenerative medical techniques and prosthetics care. An application that combines optogenetics for voluntarily stimulating nerves, imaging to visualize neural activity, and a wearable micro-instrument for implantation into the brain could meet the abovementioned demand.

Neurobiological actions by three distinct subtypes of brain-derived neurotrophic factor: Multi-ligand model of growth factor signaling.

Brain-derived neurotrophic factor (BDNF) is one of the most active members of the neurotrophin family. BDNF not only regulates neuronal survival and differentiation, but also functions in activity-dependent plasticity processes such as long-term potentiation (LTP), long-term depression (LTD), learning, and memory. Like other growth factors, BDNF is produced by molecular and cellular mechanisms including transcription and translation, and functions as a bioactive molecule in the nervous system.

Introduction of chemically labile substructures into Arabidopsis lignin through the use of LigD, the Cα-dehydrogenase from Sphingobium sp. strain SYK-6.

Bacteria-derived enzymes that can modify specific lignin substructures are potential targets to engineer plants for better biomass processability. The Gram-negative bacterium Sphingobium sp. SYK-6 possesses a Cα-dehydrogenase (LigD) enzyme that has been shown to oxidize the α-hydroxy functionalities in β-O-4-linked dimers into α-keto analogues that are more chemically labile.

Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments.

In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity (Tamura et al., 2012, 2013). In the present study, we examined whether parvalbumin (PV)-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice.

Efficient refolding and immobilization of PMMA-tag-fused single-chain Fv antibodies for sensitive immunological detection on a PMMA plate.

In this study, we investigated the efficient refolding and site-specific immobilization of single-chain variable fragments (scFvs) genetically fused with a poly(methylmethacrylate)-binding peptide (PMMA-tag). According to the results of an aggregation test of a scFv-PM in the presence of 0.5 M urea, aggregation was hardly detectable at a weak-alkaline pH (8.

Does extracellular proteolysis control mammalian cognition?

Recent advances in neuroscience techniques for analyzing synaptic functions, have revealed that even in a fully developed nervous system, dynamic structural changes in synapses can modify a variety of interactions between the presynaptic and postsynaptic neuron. Accumulating evidence suggests that extracellular proteases are involved in the structural modification of synapses through various pathways, including proteolytic cleavage at specific amino acid residues of the extracellular matrix proteins, cell adhesion molecules, and neurotrophic factors. Limited proteolysis induces changes in the properties of substrate proteins or releases functional domains (such as ligands) of the substrate proteins, which activate a signal transduction cascade, and hence could serve to initiate a variety of physiological functions.

Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice.

Background: Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood.

Processing of neuregulin-1 by neuropsin regulates GABAergic neuron to control neural plasticity of the mouse hippocampus.

Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect noncleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1 (NRG-1) proteolytic signaling system, which is specifically localized in the microdomain of synaptic cleft, in the mouse hippocampus.

Water-Soluble Derivatives of Octanuclear Iron-Oxo-Pyrazolato Complexes; An Experimental and Computational Study.

Two water-soluble iron-pyrazolato complexes, [Fe], have been prepared by the introduction of twelve hydroxyalkyl groups to the periphery of the approximately spherical octanuclear molecule and they are contrasted with their two organosoluble chloroalkyl analogues. All four new complexes, - , have been characterized in solution by H-NMR and electrospray ionization mass spectroscopy. The one-electron reduction product of the water-soluble , [Fe], has been structurally characterized by single crystal diffraction methods.

Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex.

Techniques for fast, noninvasive measurement of neuronal excitability within a broad area will be of major importance for analyzing and understanding neuronal networks and animal behavior in neuroscience field. In this research, a novel implantable imaging system for fluorescence potentiometry was developed using a complementary metal-oxide semiconductor (CMOS) technology, and its application to the analysis of cultured brain slices and the brain of a living mouse is described. A CMOS image sensor, small enough to be implanted into the brain, with light-emitting diodes and an absorbing filter was developed to enable real-time fluorescence imaging.

Screening of PC and PMMA-binding peptides for site-specific immobilization of proteins.

In the present study, we used proteomic research technology to develop a method for the screening and evaluation of material-binding peptides for protein immobilization. Using this screening method, soluble Escherichia coli proteins that preferentially adsorbed onto polycarbonate (PC) and poly(methylmethacrylate) (PMMA) as model plastic materials were first isolated and identified by 2-dimensional electrophoresis (2DE) combined with peptide mass fingerprinting (PMF). The genes of identified protein candidates (ELN, MLT, OMP, and BIF) that exhibited a hexahistidine tag (6×His-tag) were over-expressed by E.

CMOS image sensor integrated with micro-LED and multielectrode arrays for the patterned photostimulation and multichannel recording of neuronal tissue.

We developed a complementary metal oxide semiconductor (CMOS) integrated device for optogenetic applications. This device can interface via neuronal tissue with three functional modalities: imaging, optical stimulation and electrical recording. The CMOS image sensor was fabricated on 0.