Transthyretin: a review from a structural perspective

Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism of amyloid formation and detecting the variant gene in individuals at risk. Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001     

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.     

A natural allele of Nxf1 suppresses retrovirus insertional mutations

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements.     

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.     

城市--生态学最后的前沿阵地

自从产业革命以来，城市便是西方文化中一个奇特的关联到爱与恨的主题。一方面，我们对城市在文明兴起中的重要作用表示敬意；另一方面，我们为城市中连绵的大烟囱、堆积如山的垃圾和漫溢的阴沟而掩住鼻孔，责难它们恰恰是旷野的对立面。美国的哲学家、博物学家亨利·大维·梭罗写道，大自然“孤独地挥舞着，远离人类居住的城镇。”但是如果一位外星人来访，它会不会表示异议？它会不会像观察雨林和珊瑚礁一样，把城市看作是地球上另一个生态系统？它会不会注意到城市里的所有事物最终受制于同样的生物和物理进程，正是这一进程形成了每一处…     

转基因植物中反义基因对乙烯生物合成的抑制作用

乙烯调节着高等植物的许多生理和发育过程,包括果实成熟、叶脱落、衰老和伤反应.虽然在果实成熟和叶片衰老过程中,mRNA的积累与乙烯的产量以及感量相关,但控制乙烯合成的调节机制以及乙烯促进基因表达的机理并不清楚.此前我们曾报告,互补DNApTOM13与某种mRNA的作用相同,而这种mRNA的合成与趋熟果实及受伤叶片中乙烯的合成相关.pTOM13mRNA编码一种相对分子量约35000的蛋白.对cDNA和三个相关基因的克隆以及测序已经完成,但该蛋白质的作用尚未知道.我们认为,应用pTOM13时,反义RNA降低了乙烯的生物合成,降低程度与反义RNA量的多少…