Kainate excitotoxicity is mediated by AMPA- but not kainate-preferring receptors in embryonic rat hippocampal cultures

We investigated kainate-induced excitotoxicity in embryonic rat hippocampal cells cultured in a chemically defined medium. Treatment with kainate for 24 h resulted in neuronal death, as assessed by the release of lactate dehydrogenase into the culture media. This neurotoxic effect was kainate dose- and culture age-dependent. EC50 of kainate was 127 +/- 11 microM. 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (f)quinoxaline (NBQX) completely blocked the toxicity, while MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, also blocked it but not completely. Furthermore, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) attenuated the kainate injury, while the selective and noncompetitive AMPA-preferring receptor antagonist 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2,3-benzo-diazepine (GYKI 52466) blocked it completely. Concanavalin A (ConA), which potentiates the response to kainate at kainate-preferring receptors, had little effect on kainate toxicity. Further, AMPA alone induced little toxicity, but produced remarkable toxicity when cyclothazide was used to block the desensitization of AMPA-preferring receptors. These results indicate that kainate excitotoxicity in hippocampal cultures is mediated by AMPA- but not kainate-preferring receptors, and that it involves NMDA-receptor-mediated toxicity. The non-desensitizing response at AMPA-preferring receptors may play an important role in kainate-induced excitotoxicity.     

Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110beta is synergistically activated by the betagamma subunits of G proteins and phosphotyrosyl peptide

Phosphoinositide 3-kinase (PI 3-kinase) is a key signaling enzyme implicated in variety of receptor-stimulated cell responses. Receptors with intrinsic or associated tyrosine kinase activity recruit heterodimeric PI 3-kinases consisting of a 110-kDa catalytic subunit (p110) and an 85-kDa regulatory subunit (p85). We separated a PI 3-kinase that could be stimulated by the betagamma subunits of G protein (Gbetagamma) from rat liver. The Gbetagamma-sensitive PI 3-kinase appeared to be a heterodimer consisting of p110beta and p85 (or their related subunits). The stimulation by Gbetagamma was inhibited by the GDP-bound alpha subunit of the inhibitory GTP-binding protein. Moreover, the stimulatory action of Gbetagamma was markedly enhanced by the simultaneous addition of a phosphotyrosyl peptide synthesized according to the amino acid sequence of the insulin receptor substrate-1. Such enzymic properties could be observed with a recombinant p110beta/p85alpha expressed in COS-7 cells with their cDNAs. In contrast, another heterodimeric PI 3-kinase consisting of p110alpha and p85 in the same rat liver, together with a recombinant p110alpha/p85alpha, was not activated by Gbetagamma, although their activities were stimulated by the phosphotyrosyl peptide. These results indicate that p110beta/p85 PI 3-kinase may be regulated in a cooperative manner by two different types of membrane receptors, one possessing tyrosine kinase activity and the other activating GTP-binding proteins.     

Acoustic emission of composite materials in tensile tests at cryogenic temperatures

Tensile tests of fibre reinforced plastics are performed at cryogenic temperatures and simultaneously acoustic emission (AE) is observed to examine the microscopic deformation and fracture processes of these materials. AE behaviours at liquid helium temperature are different from those at liquid nitrogen temperature, although the mechanical behaviours are similar. From these results, correlations of the AE sources with the microscopic deformation and fracture processes are discussed.     

Microscopical study of frictional properties of molybdenum disulphide

The frictional properties of molybdenum disulphide were examined on a microscopic scale. A friction trace was recorded for diamond sliding on MoS₂ and scanning electron micrographs were taken from the track formed. Stick-slip occurred and produced characteristic features different from those observed for diamond sliding on stainless steel. Cleaved fragments of MoS₂ piled up and curved concavely to the direction of sliding. A change in the superficial density of sulphur corresponding to stick-slip was found by Auger scanning electron microscopy indicating its important role in reducing friction. Many edge scratching was examined, using emery paper sliding on MoS₂; the finer the abrasive particles, the better the orientation of crytallites having {0001} parallel to the surface.     

A method for estimating renal functions based on the radioisotope renogram

A method has been developed to predict or estimate the results of commonly used routine renal function tests based on a renogram. The model is built on two differential equations derived in terms of seven parameters which can be measured from tracings of radioactivity recorded on the heart, the kidneys, and the bladder. The model successfully reconstructed every possible variation of the renogram pattern by computer simulation. Expected results of the four renal function tests were computed by multiple regression equations using five out of the seven parameters as criteria variables (p less than 0.05). The four renal function tests were (1) a concentration test, (2) a PSP test, (3) the glomerular filtration rate, and (4) blood urea nitrogen.     

An 8.5-ns 112-b transmission gate adder with a conflict-free bypasscircuit

The authors discuss the weak point of a conventional bypass circuit, or carry-skip paths in a Manchester adder, and propose a new bypass circuit and its control scheme to avoid transitory fighting that causes an intermediate voltage. A 112-b transmission gate adder is presented. It uses a group of three mutually exclusive transmission gates for the carry-skip paths and a new conditional sum generation circuit. It has an estimated propagation delay time of 8.5 ns and 6941 transistors, both of which are smaller than for conventional carry select adders. The adder is integrated into an area of 0.41×3.36 mm² achieved by a 0.8-μm, triple-metal, full-CMOS process     

Experimental Evidence of Anisotropic and Stable Charged Excitons (Trions) in Atomically Thin 2D ReS2

Experimentally observed, stable trions with large binding energy (≈25 meV) in atomically thin monolayer 2D transition metal dichalcogenides MX₂ (M = Mo, W, X = S, Se, and Te) with an isotropic crystal structure have been extensively studied. In contrast, the characteristics of trions in atomically thin 2D materials with an anisotropic crystal structure are not completely understood. Low‐temperature photoluminescence (PL) spectroscopy in few‐layer ReS₂ with an anisotropic crystal structure by applying a gate voltage is described. A new PL peak that emerges below the lower‐energy side of neutral excitons obtained by tuning the gate voltages is attributed to emission from negative trions. Furthermore, the trion binding energy that is strongly dependent on the layer thickness reaches a large value of ≈60 meV in 1L–ReS₂, which is ≈2 times larger than that in other isotropic 2D materials (MX₂). The enhancement of the binding energy reflects the quasi‐1D nature of the trions in anisotropic atomically thin ReS₂. These experimental observations will promote a better understanding of the optical response and applications in new categories of the anisotropic atomically thin 2D materials with a quasi‐1D nature.     

Lithium cycling efficiency and conductivity for high dielectric solvent/low viscosity solvent mixed systems

Lithium cycling efficiency on a lithium substrate (Li-on-Li cycling) and conductivity for various mixed solvent systems of high dielectric solvent (HDS) and low viscosity solvent (LVS) were examined for secondary lithium batteries. For the HDS, sulfolane, dimethylsulfoxide, γ-lactones, propylene carbonate (PC) and ethylene carbonate (EC) were used. For the LVS, tetrahydrofuran (THF), 2-methyl-THF, 1,2-dialkoxyethanes and 1,3-dioxolane (DOL) were used. For the solute, LiAsF₆, LiBF₄, LiCF₃CO₃ and LiClO₄ were used. Lithium cycling efficiencies newly measured on a Li substrate (E_a) for EC/LVS or PC/LVS were ca 5% or 15% higher than those previously obtained by simple cycling of Li on a Pt substrate, while the order of Li cycling efficiencies to LVS change is similar in both cases, except for EC/DOL or PC/DOL. The reasons seem to be that the Li-on-Li cycling minimizes the influence of electrochemical Li/Pt alloying and partial solvent oxidation during the cycle on Li cycling efficiency. The E_a values in HDS/LVS mixed systems incorporating LiAsF₆ or LiClO₄ tended to increase with a decrease in the reactivity to Li, of not only LVS but also HDS. EC/THF systems incorporating LiAsF₆ or LiClO₄ showed high E_a values of ca 95% even by Li-on-Li cycling, the value being higher than those (ca 92%) for LiBF₄ or LiCF₃SO₃ systems. In addition, for all the HDS/LVS mixed systems examined in this work, conductivities were higher than those for HDS or LVS single solvent systems. In regard to both conductivity and Li cycling efficiency, HDS/LVS mixed systems are considered to be effective in various lithium battery applications.     

Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome

BACKGROUND: Turcot's Syndrome is the association of multiple adenomatous polyps of the colon with a primary tumor of the central nervous system. We present the first reported case of Turcot's Syndrome in a patient with malignant ependymomas. Recent advances in the elucidation of the genetic basis for the hereditary forms of colon cancer have provided a clearer understanding of the etiology of Turcot's Syndrome. This new information is relevant to the neurosurgical community and provides updated guidelines in the diagnosis and management of patients with this complex disease process. RESULTS: Turcot's Syndrome is related to two distinct genetic errors. The first involves a germ-line mutation in the adenomatous polyposis coli (APC) gene, which is postulated to act as a tumor suppressor gene. The second is a germ-line defect in one of a group of genes responsible for DNA nucleotide mismatch repair. CONCLUSION: The elucidation of the gene defects responsible for the hereditary forms of colon cancer has provided a clearer understanding of the molecular basis of Turcot's Syndrome. Patients with hereditary forms of colon cancer and neurologic symptoms require immediate and thorough investigation because of their significantly increased risk of developing CNS tumors. Previously healthy patients diagnosed with a CNS tumor with a family history of adenomatous polyposis coli should undergo screening and surveillance colonoscopy as the CNS lesion may precede colonic symptoms. CNS screening guidelines for asymptomatic patients with adenomatous polyposis coli requires further risk analysis studies. All patients diagnosed with Turcot's Syndrome should be tested for the gene defect, including the CNS tumor tissue to provide further data on the genetic relationship between Turcot's Syndrome and the hereditary forms of colon cancer.     

Identification of Chimeric αβγ Diterpene Synthases Possessing both Type II Terpene Cyclase and Prenyltransferase Activities

Two unusual diterpene synthases composed of three domains (α, β, and γ) were identified from fungal Penicillium species. They are the first enzymes found to possess both type II terpene cyclase (TC) and prenyltransferase (PT) activities. These enzymes were characterized by heterologous expression in Aspergillus oryzae and in vitro experiments with wild-type, mutated, and truncated enzymes. The results revealed that the α domain in the C-terminal region of these enzymes was responsible for the PT activity, whereas the βγ domains in the N-terminal region composed the type II TC, and formed copalyl diphosphate ( 2 ). Additionally, between the α and βγ domains, there is a characteristic linker region, in which minimal secondary structure is predicted. This linker does not exist in the characterized three-domain (αβγ) terpene synthases known as monofunctional type I or type II TCs, or bifunctional type I and type II TC enzymes. Therefore, both the catalytic activities and protein architecture substantially differentiate these new enzymes from the previously characterized terpene synthases.