Degeneration of retinal neuroblasts by chinoform-ferric chelate

The possible mechanism of neuropathic effect of chinoform was investigated using cultured retinal neuroblasts from chick embryos. Retinal neuroblasts completely degenerated by chinoform-ferric chelate within a day. This change, however,, was not observed with free chinoform or ferric ion alpha-Tocopherol had a potent protective effect on the toxicity of the chelate. From these results, it was concluded that the lipid peroxidation due to ferric ion chelated with chinoform incorporated into the membrane of nerve tissues is the most important step in induction of the neuropathy.     

Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D

Small, compact genomes of ultrasmall unicellular algae provide information on the basic and essential genes that support the lives of photosynthetic eukaryotes, including higher plants. Here we report the 16,520,305-base-pair sequence of the 20 chromosomes of the unicellular red alga Cyanidioschyzon merolae 10D as the first complete algal genome. We identified 5,331 genes in total, of which at least 86.3% were expressed. Unique characteristics of this genomic structure include: a lack of introns in all but 26 genes; only three copies of ribosomal DNA units that maintain the nucleolus; and two dynamin genes that are involved only in the division of mitochondria and plastids. The conserved mosaic origin of Calvin cycle enzymes in this red alga and in green plants supports the hypothesis of the existence of single primary plastid endosymbiosis. The lack of a myosin gene, in addition to the unexpressed actin gene, suggests a simpler system of cytokinesis. These results indicate that the C. merolae genome provides a model system with a simple gene composition for studying the origin, evolution and fundamental mechanisms of eukaryotic cells.     

Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases

Hematopoiesis is hierarchically orchestrated by a very small population of hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are tightly regulated to maintain homeostatic blood production. HSCs are predominantly quiescent, but they enter the cell cycle in response to inflammatory signals evoked by severe systemic infection or injury. Thus, hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen recognition receptors and proinflammatory cytokines to induce emergency myelopoiesis during infection. This emergency myelopoiesis counterbalances the loss of cells and generates lineage-restricted hematopoietic progenitors, eventually replenishing mature myeloid cells to control the infection. Controlled generation of such signals effectively augments host defense, but dysregulated stimulation by these signals is harmful to HSPCs. Such hematopoietic failure often results in blood disorders including chronic inflammatory diseases and hematological malignancies. Recently, we found that interleukin (IL)-27, one of the IL-6/IL-12 family cytokines, has a unique ability to directly act on HSCs and promote their expansion and differentiation into myeloid progenitors. This process resulted in enhanced production of neutrophils by emergency myelopoiesis during the blood-stage mouse malaria infection. In this review, we summarize recent advances in the regulation of myelopoiesis by proinflammatory cytokines including type I and II interferons, IL-6, IL-27, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in infectious diseases.     

OCIAD2 activates γ-secretase to enhance amyloid β production by interacting with nicastrin

The gamma (γ)-secretase holoenzyme is composed of four core proteins and cleaves APP to generate amyloid beta (Aβ), a key molecule that causes major neurotoxicity during the early stage of Alzheimer’s disease (AD). However, despite its important role in Aβ production, little is known about the regulation of γ-secretase. OCIAD2, a novel modulator of γ-secretase that stimulates Aβ production, and which was isolated from a genome-wide functional screen using cell-based assays and a cDNA library comprising 6,178 genes. Ectopic expression of OCIAD2 enhanced Aβ production, while reduction of OCIAD2 expression suppressed it. OCIAD2 expression facilitated the formation of an active γ-secretase complex and enhanced subcellular localization of the enzyme components to lipid rafts. OCIAD2 interacted with nicastrin to stimulate γ-secretase activity. OCIAD2 also increased the interaction of nicastrin with C99 and stimulated APP processing via γ-secretase activation, but did not affect Notch processing. In addition, a cell-permeable Tat-OCIAD2 peptide that interfered with the interaction of OCIAD2 with nicastrin interrupted the γ-secretase-mediated AICD production. Finally, OCIAD2 expression was significantly elevated in the brain of AD patients and PDAPP mice. This study identifies OCIAD2 as a selective activator of γ-secretase to increase Aβ generation.     

Lipid peroxidation caused by chinoform-ferric chelate in cultured neural retinal cells

Summary Incorporation of chinoform-ferric chelate was demonstrable in cultured neural retinal cells of chick embryos after 1 h of incubation, and the lipid peroxide level in the cells was increased strikingly 1 h thereafter. On the other hand, free ferric ions were scarcely incorporated into the cells, and a significant increase in the lipid peroxide level in the cells was not observed. These data indicate that chinoform is carrier of iron for its passage through cell membranes and that the incorporated iron induces lipid peroxidation which in turn leads to neural cell degeneration.This work was supported in part by a grant from the Ministry of Health and Welfare of Japan     

Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues

It has been shown previously that deoxyguanosine residues in DNA are hydroxylated at the C-8 position both in vitro and in vivo to produce 8-hydroxydeoxyguanosine (8-OH-dG) by various agents that produce oxygen radicals such as reducing reagents-O2, metal ions-O2, polyphenol-H2O2-Fe3+, asbestos-H2O2 or ionizing radiation. These agents are mostly either mutagenic or carcinogenic; therefore, the formation of 8-OH-dG can also be considered a likely cause of mutation or carcinogenesis by oxygen radicals. It is of interest to know whether the 8-OH-dG residue in DNA is misread during DNA replication. To answer this question, we have examined the effect of the 8-OH-dG residue in DNA on the fidelity of DNA replication using a DNA synthesis system in vitro with Escherichia coli DNA polymerase I (Klenow fragment). The synthetic oligodeoxynucleotides, with or without an 8-OH-dG residue in a specified position, were chemically synthesized and used as templates for DNA synthesis under the conditions of the dideoxy chain termination sequencing method. Surprisingly, in addition to misreading of the 8-OH-dG residue itself, pyrimidines next to the 8-OH-dG residue (G has not yet been tested) were also misread.     

Degeneration of retinal neuroblasts by chinoform-ferric chelate

Summary The possible mechanism of neuropathic effect of chinoform was investigated using cultured retinal neuroblasts from chick embryos. Retinal neuroblasts completely degenerated by chinoform-ferric chelate within a day. This change, however, was not observed with free chinoform or ferric ion.a-Tocopherol had a potent protective effect on the toxicity of the chelate. From these results, it was concluded that the lipid peroxidation due to ferric ion chelated with chinoform incorporated into the membrane of nerve tissues is the most important step in induction of the neuropathy.This work was supported in part by a grant from the Ministry of Health and Welfare of Japan.Correspondence should be addressed to K. Yagi, Institute of Biochemistry, Faculty of Medicine, University of Nagoya, Nagoya 466, Japan.     

在MgO(001)基板上生长连续的L10-FePt 纳米薄膜

用磁控溅射法在加热到400℃的MgO(001)基片上沉积了总厚度为25 nm 的[Fe(0.6 nm)/Fe_30.5Pt_69.5(1.9nm)]₁₀ 多层连续薄膜, 并对其在[500, 900]℃的温度范围进行了3h 的真空热处理. 结果表明, 薄膜在沉积过程中发生了层间扩散, 形成A1 相的FePt 合金, 表现为软磁特性; 热处理温度高于700℃时, 薄膜内形成L1₀ 相的(001)织构, 其单轴磁晶各向异性能高于2.5×10⁷ erg cc^-1; 薄膜能在800℃以下保持形貌连续. 借助于半导体载流子扩散和复合模型, 对薄膜在高温下形貌保持连续的机理进行了探讨. 分析认为, 虽然薄膜在沉积过程中发生了层间扩散, 但内部仍然残存微弱的周期性成分起伏, 这可以有效阻碍热处理过程中因相变而引起的Pt 元素析出, 从而抑制了因形成富Pt 晶界而导致的形貌不连续. 这种薄膜可以方便地用于微加工制作磁性阵列和隧道结.