ABSTRACT
Dendritic spines function as microcompartments that can modify the efficiency of their associated synapses. Here, we analyzed stimulus-dependent molecular changes in spines. The F-actin capping protein CapZ accumulates in parts of dendritic spines within regions where long-term potentiation has been induced. We produced a transgenic mouse line, AiCE-Tg, in which CapZ tagged with enhanced green fluorescence protein (EGFP-CapZ) is expressed. Twenty minutes after unilateral visual or somatosensory stimulation in AiCE-Tg mice, relative EGFP-CapZ signal intensification was seen in a subset of dendritic spines selectively in stimulated-side cortices; this right-left difference was abolished by NMDA receptor blockade. Immunolabeling of α-actinin, a PSD-95 binding protein that can recruit AMPA receptors, showed that the α-actinin signals colocalized more frequently in spines with the brightest EGFP-CapZ signals (top 100) than in spines with more typical EGFP-CapZ signal strength (top 1,000). This stimulus-dependent in vivo redistribution of EGFP-CapZ represents a novel molecular event with plasticity-like characteristics, and bright EGFP-CapZ in AiCE-Tg mice make high-CapZ spines traceable in vivo and ex vivo. This mouse line has the potential to be used to reveal sequential molecular events, including synaptic tagging, and to relate multiple types of plasticity in these spines, extending knowledge related to memory mechanisms.
Subject(s)
Brain/metabolism , Dendritic Spines/metabolism , Actinin/metabolism , Animals , Disks Large Homolog 4 Protein/metabolism , Green Fluorescent Proteins/metabolism , Mice , Mice, Inbred C57BL , Neurons/metabolism , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Signal Transduction/physiology , Synapses/metabolismABSTRACT
The absolute stereostructure of komodoquinone A (1), a neuritogenic anthracycline, which was isolated from a cultured marine Streptomyces sp. KS3, has been determined on the basis of chemical derivatization. Komodoquinone A (1) induces neuronal cell differentiation in the neuroblastoma cell line, Neuro 2A and arrests the cell cycle at the G1 phase. The effect of a solid-state medium on the production of 1 and its aglycone, komodoquinone B (2), was examined.
Subject(s)
Anthracyclines/chemistry , Anthraquinones/chemistry , Streptomyces/chemistry , Animals , Anthracyclines/isolation & purification , Anthracyclines/pharmacology , Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Cell Cycle/drug effects , Cell Cycle/physiology , Cell Line, Tumor , Fermentation , Mice , Seawater/microbiology , Stereoisomerism , Streptomyces/growth & developmentABSTRACT
A novel anthracycline, komodoquinone A (1), and its aglycone, komodoquinone B (2), were isolated from the solid-state fermentation of the marine Streptomyces sp. KS3, which was isolated from marine sediment. The absolute stereostructures of 1 and 2, except for the sugar portion, were elucidated on the basis of chemical and physicochemical evidence. Komodoquinone A (1) is a unique anthracycline, in which a new amino sugar is connected to the D-ring of the anthracyclinone skeleton, and was found to induce neuronal cell differentiation in the neuroblastoma cell line, Neuro 2A.
Subject(s)
Anthraquinones/isolation & purification , Nerve Growth Factor/isolation & purification , Streptomyces/chemistry , Anthraquinones/chemistry , Anthraquinones/pharmacology , Indonesia , Molecular Structure , Nerve Growth Factor/chemistry , Nerve Growth Factor/pharmacology , Neuroblastoma , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity Relationship , Tumor Cells, Cultured/drug effectsABSTRACT
We examined the bone movement in the forepaw and hind paw in the aardvark (Orycteropus afer) by using three-dimensional (3D)-computed tomography (CT) techniques and osteometrical methods to confirm the functional adaptation of the extremities as a digging system. The four metacarpal bones could be strongly bent from the distal carpal bones. The distal end of the second and third metacarpal bones possessed enlarged smooth articulation surfaces that allowed the proximal phalanx to bend at a sharp angle. However, the articulation surface was not well-developed in the distal end of the fourth and fifth metacarpal bones and the proximal phalanx could bend at smaller angle in these two lateral digits. The proximal phalanges sharply crook from the metatarsal in the first, second, third and fourth digits in the hind paw. We suggest that the medial two digits in the forepaw directly contribute to the crushing, when these proximal phalanges crook in the phase of power stroke. In contrast the lateral third and fourth digits may act as sweeper of the crushed soil. These suggestions regarding the different functional adaptation between medial two digits and lateral two digits are consistent with the anatomical data of the forearm musculature. In the hind paw, we suggest that the second, third and fourth digits are functionally similar and that the hind paw may not act as a crushing apparatus but as a running motor or soil-sweeper similarly using these main three digits.
Subject(s)
Metacarpus/physiology , Metatarsal Bones/physiology , Motor Activity/physiology , Xenarthra/anatomy & histology , Animals , Forelimb/anatomy & histology , Image Processing, Computer-Assisted , Metacarpus/anatomy & histology , Metacarpus/diagnostic imaging , Metatarsal Bones/anatomy & histology , Metatarsal Bones/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
Lembehsterols A (1) and B (2), two novel sulfated sterols, were isolated from the marine sponge Petrosia strongylata. Both sterols showed inhibitory activity against thymidine phosphorylase, which is an enzyme related to angiogenesis in solid tumors. The structures of these sulfated sterols were established on the basis of chemical and physicochemical evidence.
