Mechanisms for interferon-α-induced depression and neural stem cell dysfunction.

New neurons generated by the neural stem cells (NSCs) in the adult hippocampus play an important role in emotional regulation and respond to the action of antidepressants. Depression is a common and serious side effect of interferon-α (IFN-α), which limits its use as an antiviral and antitumor drug. However, the mechanism(s) underlying IFN-induced depression are largely unknown.

Over-expression of carbon monoxide dehydrogenase-I with an accessory protein co-expression: a key enzyme for carbon dioxide reduction.

Carbon monoxide dehydrogenase-I (CODH-I) from the CO-utilizing bacterium Carboxydothermus hydrogenoformans are expected to be utilized as a part of reproducible carbon dioxide photoreduction system. However, the over-expression system for CODH-I remains to be constructed. CODH-I constitutes a hydrogenase/CODH gene cluster including a gene encoding a Ni-insertion accessory protein, CooC (cooC3).

Quantitative structure-cytotoxicity relationship of phenylpropanoid amides.

Background: A total of 12 phenylpropanoid amides were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to investigate on their biological activities.

Materials And Methods: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor selectivity was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal oral cells to that against OSCC cell lines.

Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus.

Background: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg2+ block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg2+ block causes perinatal lethality. In this study, we used a brain-region specific knock-in mouse expressing an NMDA receptor that is defective for the Mg2+ block in order to test its role in neural information processing.

Transcriptomic evidence for immaturity of the prefrontal cortex in patients with schizophrenia.

Background: Schizophrenia, a severe psychiatric disorder, has a lifetime prevalence of 1%. The exact mechanisms underlying this disorder remain unknown, though theories abound. Recent studies suggest that particular cell types and biological processes in the schizophrenic cortex have a pseudo-immature status in which the molecular properties partially resemble those in the normal immature brain.

Experimental and theoretical approaches to redox innocence of ligands in uranyl complexes: what is formal oxidation state of uranium in reductant of uranyl(VI)?

Redox behavior of [UO2(gha)DMSO](-)/UO2(gha)DMSO couple (gha = glyoxal bis(2-hydroxanil)ate, DMSO = dimethyl sulfoxide) in DMSO solution was investigated by cyclic voltammetry and UV-vis-NIR spectroelectrochemical technique, as well as density functional theory (DFT) calculations. [UO2(gha)DMSO](-) was found to be formed via one-electron reduction of UO2(gha)DMSO without any successive reactions. The observed absorption spectrum of [UO2(gha)DMSO](-), however, has clearly different characteristics from those of uranyl(V) complexes reported so far.

Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes.

Background: We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved.

Results: We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses.

Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia.

Background: Loss of adenomatous polyposis coli (APC) gene function results in constitutive activation of the canonical Wnt pathway and represents the main initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to participate in a wide spectrum of biological functions via its different functional domains and is abundantly expressed in the brain as well as in peripheral tissues. However, the neuronal function of APC is poorly understood.

Contextual and cued fear conditioning test using a video analyzing system in mice.

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue.

Identification of a novel aminopropyltransferase involved in the synthesis of branched-chain polyamines in hyperthermophiles.

Longer- and/or branched-chain polyamines are unique polycations found in thermophiles. N(4)-aminopropylspermine is considered a major polyamine in Thermococcus kodakarensis. To determine whether a quaternary branched penta-amine, N(4)-bis(aminopropyl)spermidine, an isomer of N(4)-aminopropylspermine, was also present, acid-extracted cytoplasmic polyamines were analyzed by high-pressure liquid chromatography, gas chromatography (HPLC), and gas chromatography-mass spectrometry.

Extraction of Pd(II), Rh(III) and Ru(III) from HNO(3) aqueous solution to betainium bis(trifluoromethanesulfonyl)imide ionic liquid.

Extraction efficiencies of Pd(ii), Rh(iii), and Ru(iii) from HNO3(aq) to [Hbet][Tf2N] were demonstrated, i.e., Pd(ii) is the most extractable, Rh(iii) is medium extractable, and Ru(iii) is the least extractable.

Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice.

Cluster of differentiation 47 (CD47) is a member of the immunoglobulin superfamily which functions as a ligand for the extracellular region of signal regulatory protein α (SIRPα), a protein which is abundantly expressed in the brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various functions in the central nervous system (CNS), such as the modulation of synaptic transmission and neuronal cell survival. We previously reported that CD47 is involved in the regulation of depression-like behavior of mice in the forced swim test through its modulation of tyrosine phosphorylation of SIRPα.

Development of irreversible inactivators of spermine oxidase and N1-acetylpolyamine oxidase.

Three functional groups (2-propenyl, 2-propynyl, and 2,3-butadienyl) were introduced onto one of the terminal amino groups of spermidine. Of the six compounds synthesized, N-(3-aminopropyl)-N'-2,3-butadienyl-1,4-butanediamine (N(8)-butadienyl Spd) and N-[3-(2,3-butadienylamino)propyl]-1,4-butanediamine (N(1)-butadienyl Spd) irreversibly inactivated human spermine oxidase (SMO) and N(1)-acetylpolyamine oxidase (APAO). Interestingly, N(8)-butadienyl Spd inactivated SMO far more potently than N,N'-di-2,3-butadienyl-1,4-butanediamine (MDL 72527).

Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders.

Background: We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system.

Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition.

Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1 (-/-) mice exhibited behavioral abnormalities related to schizophrenia. The crmp1 (-/-) mice exhibited hyperactivity and/or impaired emotional behavioral phenotype.

PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.

The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy suggests a shared underlying genetic susceptibility; several genes, when mutated, can contribute to both disorders. Recently, PRICKLE1 missense mutations were found to segregate with ASD. However, the mechanism by which mutations in this gene might contribute to ASD is unknown.

Total synthesis of (+)-clavilactone A and (-)-clavilactone B by ring-opening/ring-closing metathesis.

The enantioselective total synthesis of natural enantiomers of clavilactones A and B has been achieved. A key feature of the synthesis is the use of a ring-opening/ring-closing metathesis, which allows the one-pot transformation of a strained cyclobutenecarboxylate into a γ-butenolide.

Point mutation in syntaxin-1A causes abnormal vesicle recycling, behaviors, and short term plasticity.

Syntaxin-1A is a t-SNARE that is involved in vesicle docking and vesicle fusion; it is important in presynaptic exocytosis in neurons because it interacts with many regulatory proteins. Previously, we found the following: 1) that autophosphorylated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an important modulator of neural plasticity, interacts with syntaxin-1A to regulate exocytosis, and 2) that a syntaxin missense mutation (R151G) attenuated this interaction. To determine more precisely the physiological importance of this interaction between CaMKII and syntaxin, we generated mice with a knock-in (KI) syntaxin-1A (R151G) mutation.

Cysteine 295 indirectly affects Ni coordination of carbon monoxide dehydrogenase-II C-cluster.

A unique [Ni-Fe-S] cluster (C-cluster) constitutes the active center of Ni-containing carbon monoxide dehydrogenases (CODHs). His(261), which coordinates one of the Fe atoms with Cys(295), is suggested to be the only residue required for Ni coordination in the C-cluster. To evaluate the role of Cys(295), we constructed CODH-II variants.

Expression and localization of taste receptor genes in the vallate papillae of rats: effect of zinc deficiency.

Conclusion: We found a difference in expression sites between TAS2Rs and ENaC (epithelial sodium channels). The number of TAS2R-positive cells and ENaC-positive cells were decreased in zinc-deficient diet rats. These findings suggest that decreased expression of taste receptor genes may play an important role in the onset of zinc deficiency-associated taste disorder.

Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice.

Background: In autosomal recessive early-onset Parkinsonism (PARK2), the pathogenetic process from the loss of function of a ubiquitin ligase parkin to the death of dopamine neurons remains unclear. A dominant hypothesis attributes the neurotoxicity to accumulated substrates that are exempt from parkin-mediated degradation. Parkin substrates include two septins; SEPT4/CDCrel-2 which coaggregates with α-synuclein as Lewy bodies in Parkinson's disease, and its closest homolog SEPT5/CDCrel-1/PNUTL1 whose overload with viral vector can rapidly eliminate dopamine neurons in rats.

Uranyl-halide complexation in N,N-dimethylformamide: halide coordination trend manifests hardness of [UO2]2+.

Complexation of [UO2](2+) with Cl(-), Br(-), and I(-) in N,N-dimethylformamide (DMF) was studied by UV-vis absorption spectroscopy and extended X-ray absorption fine structure (EXAFS) to clearly differentiate halide coordination strengths to [UO2](2+). In the Cl(-) system, it was clarified that the Cl(-) coordination to [UO2](2+) in DMF proceeds almost quantitatively. The coordination number of Cl(-) almost quantitatively increases up to 4, i.

Immature dentate gyrus: an endophenotype of neuropsychiatric disorders.

Adequate maturation of neurons and their integration into the hippocampal circuit is crucial for normal cognitive function and emotional behavior, and disruption of this process could cause disturbances in mental health. Previous reports have shown that mice heterozygous for a null mutation in α -CaMKII, which encodes a key synaptic plasticity molecule, display abnormal behaviors related to schizophrenia and other psychiatric disorders. In these mutants, almost all neurons in the dentate gyrus are arrested at a pseudoimmature state at the molecular and electrophysiological levels, a phenomenon defined as "immature dentate gyrus (iDG).

ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response.

Background: The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1(Rgsc174)/Grin1+) that has a non-synonymous mutation in Grin1.

Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice.

Background: Synaptosomal-associated protein, 25 kDa (SNAP-25) regulates the exocytosis of neurotransmitters. Growing evidence suggests that SNAP-25 is involved in neuropsychiatric disorders, such as schizophrenia, attention-deficit/hyperactivity disorder, and epilepsy. Recently, increases in anxiety-related behaviors and epilepsy have been observed in SNAP-25 knock-in (KI) mice, which have a single amino acid substitution of Ala for Ser187.