多聚酶链反应（PCR）的应用：有机体和群体生物学

在过去的15年内,重组DNA技术的发展使得人们能在分子水平上对特殊的基因作详细地研究。生物科学的许多领域如遗传学、分子生物学、细胞生物学和发育生物学所获得的成果都是巨大的,这些进展的取得是对一定量的物种主要是人、鼠、果蝇、酵母和大肠杆菌的基因结构作充分分析的结果。     

Silicon in the Earth's core

Small isotopic differences between the silicate minerals in planets may have developed as a result of processes associated with core formation, or from evaporative losses during accretion as the planets were built up. Basalts from the Earth and the Moon do indeed appear to have iron isotopic compositions that are slightly heavy relative to those from Mars, Vesta and primitive undifferentiated meteorites (chondrites). Explanations for these differences have included evaporation during the 'giant impact' that created the Moon (when a Mars-sized body collided with the young Earth). However, lithium and magnesium, lighter elements with comparable volatility, reveal no such differences, rendering evaporation unlikely as an explanation. Here we show that the silicon isotopic compositions of basaltic rocks from the Earth and the Moon are also distinctly heavy. A likely cause is that silicon is one of the light elements in the Earth's core. We show that both the direction and magnitude of the silicon isotopic effect are in accord with current theory based on the stiffness of bonding in metal and silicate. The similar isotopic composition of the bulk silicate Earth and the Moon is consistent with the recent proposal that there was large-scale isotopic equilibration during the giant impact. We conclude that Si was already incorporated as a light element in the Earth's core before the Moon formed.     

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

Complex gas hydrate from the Cascadia margin

Natural gas hydrates are a potential source of energy and may play a role in climate change and geological hazards. Most natural gas hydrate appears to be in the form of 'structure I', with methane as the trapped guest molecule, although 'structure II' hydrate has also been identified, with guest molecules such as isobutane and propane, as well as lighter hydrocarbons. A third hydrate structure, 'structure H', which is capable of trapping larger guest molecules, has been produced in the laboratory, but it has not been confirmed that it occurs in the natural environment. Here we characterize the structure, gas content and composition, and distribution of guest molecules in a complex natural hydrate sample recovered from Barkley canyon, on the northern Cascadia margin. We show that the sample contains structure H hydrate, and thus provides direct evidence for the natural occurrence of this hydrate structure. The structure H hydrate is intimately associated with structure II hydrate, and the two structures contain more than 13 different hydrocarbon guest molecules. We also demonstrate that the stability field of the complex gas hydrate lies between those of structure II and structure H hydrates, indicating that this form of hydrate is more stable than structure I and may thus potentially be found in a wider pressure-temperature regime than can methane hydrate deposits.     

Podocalyxin enhances the adherence of cells to platelets

Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium, progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed in glycomutant CHO cells deficient in sialic acid. Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007