The future of ageing

Advances in our knowledge of age-associated diseases have far outpaced advances in our understanding of the fundamental ageing processes that underlie the vulnerability to these pathologies. If we are to increase human life expectancy beyond the fifteen-year limit that would result if today's leading causes of death were resolved, more attention must be paid to basic research on ageing. Determination of longevity must be distinguished from ageing to take us from the common question of why we age to a more revealing question that is rarely posed: why do we live as long as we do? But if the ability to intervene in ageing ever becomes a reality, it will be rife with unintended and undesirable consequences.     

A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome

Hallervorden-Spatz syndrome (HSS) is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals iron deposits in the basal ganglia. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed. Thus, understanding the biochemical defect in HSS may provide key insights into the regulation of iron metabolism and its perturbation in this and other neurodegenerative diseases. Here we show that HSS is caused by a defect in a novel pantothenate kinase gene and propose a mechanism for oxidative stress in the pathophysiology of the disease.     

Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta

Inhibin, a specific and potent polypeptide inhibitor of the secretion of follicle-stimulating hormone (FSH), of gonadal origin and thus a potential contraceptive, may constitute a missing link in the mechanism controlling the differential secretion of the pituitary gonadotropins. Inhibin-like bioactivity has been reported in various fluids and extracts of testis and in ovarian follicular fluid. Although there have been several attempts to purify inhibin from seminal plasma, purification from follicular fluid has been more successful (refs 14-16; for review see ref. 17). We have previously isolated two forms (A and B) of inhibin from porcine follicular fluid. Each form comprised two dissimilar subunits of relative molecular mass (Mr) 18,000 (18K, referred to here as the alpha-subunit) and 14K (the beta-subunit), crosslinked by one or more disulphide bridge(s). Forms A and B differ in the N-terminal sequence of their 14K subunit. Preliminary structural characterization of porcine and bovine ovarian inhibins shows that they have similar properties. Here, we have used the N-terminal amino-acid sequence data on the subunits of each inhibin to identify cloned complementary DNAs encoding the biosynthetic precursors and report that inhibins are the product of a gene family that also includes transforming growth factor-beta (TGF-beta) and whose structural organization is similar to that of pituitary and placental glycoprotein hormones.     

Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations

Kirsten (Ki)-ras cDNA clones were prepared from human lung and colon carcinoma cell lines expressing an activated c-Ki-ras2 gene. DNA sequence analysis and transfection studies indicate that different point mutations at the same codon can activate the gene; that most human c-Ki-ras2 mRNA uses sequences from a fourth coding exon distinct from that of its viral counterpart; and that at least one cell line is functionally homozygous for the activated gene.     

Insulin-like growth factor II precursor gene organization in relation to insulin gene family

The insulin gene family, comprised of insulin, relaxin, insulin-like growth factors I and II (IGF-I and IGF-II) and possibly the beta-subunit of 7S nerve growth factor, represents a group of structurally related polypeptides whose biological functions have diverged. The IGFs, or somatomedins, constitute a class of polypeptides that have a key role in pre-adolescent mammalian growth (see ref. 4 for review). IGF-I expression is regulated by growth hormone and mediates postnatal growth, while IGF-II appears to be induced by placental lactogen during prenatal development. The primary structures of both human IGFs have been determined and are closely related. A polypeptide highly homologous to human IGF-II is secreted by the rat liver cell line, BRL-3A. As this polypeptide, termed multiplication stimulating activity (MSA), differs from human IGF-II by only five amino acid residues, MSA probably represents the rat IGF-II protein. Using molecular cloning techniques, we have isolated cDNA and chromosomal genes coding for the MSA and human IGF-II precursors, respectively. Our data, presented here, indicate that both MSA and human IGF-II are synthesized initially as larger precursor molecules. The deduced preprohormones both have molecular weights (MWs) of 20,100 and contain C-terminal propeptides of 89 amino acid residues, which we have named E-peptides. The organization of the IGF-II precursor gene is discussed in relation to that of other insulin gene family members.     

Pixel switching of epitaxial Pd/YHx/CaF2 switchable mirrors

Exposure of rare-earth films to hydrogen can induce a metal-insulator transition, accompanied by pronounced optical changes. This 'switchable mirror' effect has received considerable attention from theoretical, experimental and technological points of view. Most systems use polycrystalline films, but the synthesis of yttrium-based epitaxial switchable mirrors has also been reported. The latter form an extended self-organized ridge network during initial hydrogen loading, which results in the creation of micrometre-sized triangular domains. Here we observe homogeneous and essentially independent optical switching of individual domains in epitaxial switchable mirrors during hydrogen absorption. The optical switching is accompanied by topographical changes as the domains sequentially expand and contract; the ridges block lateral hydrogen diffusion and serve as a microscopic lubricant for the domain oscillations. We observe the correlated changes in topology and optical properties using in situ atomic force and optical microscopy. Single-domain phase switching is not observed in polycrystalline films, which are optically homogeneous. The ability to generate a tunable, dense pattern of switchable pixels is of technological relevance for solid-state displays based on switchable mirrors.     

大叶白麻叶化学成分的研究

从大叶白麻[poacynumhendersonii(Hookf)woodson]叶中分得2个木脂素类化舍物,经理化常数测定和光谱分析,分别鉴定为(-)-丁香脂素[(-)-Syringaresino1]和( )-松脂素-4-O-β-D-葡萄糖甙[( )-Pinoresionol-4-0-β-D-glucopyranoside].     

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.