Circadian variation of the streptozotocin-diabetogenic effect in mice.

Streptozotocin was injected in normal mice every 4 h, during the day. Greatest number of diabetic animals were obtained at 16.00 h (95%) and lowest at 08.00 h (50%). Magnitude of hyperglycemia also showed similar distribution. This effect might be considered when planning its use for both experimental and clinical purposes.     

Asymmetric and symmetric stem-cell divisions in development and cancer

Much has been made of the idea that asymmetric cell division is a defining characteristic of stem cells that enables them to simultaneously perpetuate themselves (self-renew) and generate differentiated progeny. Yet many stem cells can divide symmetrically, particularly when they are expanding in number during development or after injury. Thus, asymmetric division is not necessary for stem-cell identity but rather is a tool that stem cells can use to maintain appropriate numbers of progeny. The facultative use of symmetric or asymmetric divisions by stem cells may be a key adaptation that is crucial for adult regenerative capacity.     

Stoichiometry and turnover in single, functioning membrane protein complexes

Many essential cellular processes are carried out by complex biological machines located in the cell membrane. The bacterial flagellar motor is a large membrane-spanning protein complex that functions as an ion-driven rotary motor to propel cells through liquid media. Within the motor, MotB is a component of the stator that couples ion flow to torque generation and anchors the stator to the cell wall. Here we have investigated the protein stoichiometry, dynamics and turnover of MotB with single-molecule precision in functioning bacterial flagellar motors in Escherichia coli. We monitored motor function by rotation of a tethered cell body, and simultaneously measured the number and dynamics of MotB molecules labelled with green fluorescent protein (GFP-MotB) in the motor by total internal reflection fluorescence microscopy. Counting fluorophores by the stepwise photobleaching of single GFP molecules showed that each motor contains approximately 22 copies of GFP-MotB, consistent with approximately 11 stators each containing two MotB molecules. We also observed a membrane pool of approximately 200 GFP-MotB molecules diffusing at approximately 0.008 microm2 s(-1). Fluorescence recovery after photobleaching and fluorescence loss in photobleaching showed turnover of GFP-MotB between the membrane pool and motor with a rate constant of the order of 0.04 s(-1): the dwell time of a given stator in the motor is only approximately 0.5 min. This is the first direct measurement of the number and rapid turnover of protein subunits within a functioning molecular machine.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.     

2003年秋冬季西安大气中有机碳和元素碳的理化特征及其来源解析

2003年9月至2004年2月在西安站点开展了大气PM2.5和PM10中碳气溶胶的连续观测,并采集了三类主要污染来源样品(燃煤,机动车尾气和生物质燃烧)进行对比分析,采用IMPROVE-TOR方法准确地测量了样品的有机碳(OC),元素碳(EC)及其中的8个碳组分含量.西安秋季和冬季大气PM2.5中OC的平均含量ρOC分别为(34.1±18.0),(61.9±33.2)μg·m-3,EC的平均含量ρEC为(11.3±6.9),(12.3±5.3)μg·m-3.OC和EC均主要赋存于PM2.5粒级中.秋季OC和EC的相关性好(R2＞0.90),冬季一般(R2=0.66).总碳气溶胶在秋季PM2.5中占(48.8±10.1)%,在冬季也达到了(45.9±7.5)%.所有观测日的ρOC/ρEC比值均大于2.0,秋季PM2.5中ρOC/ρEC平均为3.3,冬季为5.1,这可能主要与直接排放来源有关.由碳气溶胶的8个碳组分数据,采用绝对主分量分析获得了主要排放来源对总碳的贡献份额,即秋季汽油车尾气占73%,柴油车尾气占23%,生物质燃烧占4%,而冬季燃煤占了44%,汽油车尾气占44%,生物质燃烧占9%,柴油车占3%.     

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.