Totally synthetic (±)-13-Alkyl-3-hydroxy and methoxy-gona-1,3,5(10)-trien-17-ones and related compounds

Zusammenfassung Von mehreren (±) 3-Oxy- und (±) 3-Methoxy-13-alkylgona-1,3,5(10)trien-17-onen und verwandten Verbindungen, einschliesslich von Vertretern der (±) 13-Alkylgon-4-en-3-on-Reihe, werden Totalsynthese und biologische Wirksamkeit beschrieben.     

Induction of angiogenesis during the transition from hyperplasia to neoplasia

It is now well established that unrestricted growth of tumours is dependent upon angiogenesis. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types is providing a new format for studying multi-step tumorigenesis. In one of these models, transgenic mice expressing an oncogene in the beta-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novel in vitro assay confirms that hyperplasia per se does not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenic in vitro at a time when such islets are neovascularized in vivo and at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.     

Effect of iron supply on Southern Ocean CO2 uptake and implications for glacial atmospheric CO2

Photosynthesis by marine phytoplankton in the Southern Ocean, and the associated uptake of carbon, is thought to be currently limited by the availability of iron. One implication of this limitation is that a larger iron supply to the region in glacial times could have stimulated algal photosynthesis, leading to lower concentrations of atmospheric CO2. Similarly, it has been proposed that artificial iron fertilization of the oceans might increase future carbon sequestration. Here we report data from a whole-ecosystem test of the iron-limitation hypothesis in the Southern Ocean, which show that surface uptake of atmospheric CO2 and uptake ratios of silica to carbon by phytoplankton were strongly influenced by nanomolar increases of iron concentration. We use these results to inform a model of global carbon and ocean nutrients, forced with atmospheric iron fluxes to the region derived from the Vostok ice-core dust record. During glacial periods, predicted magnitudes and timings of atmospheric CO2 changes match ice-core records well. At glacial terminations, the model suggests that forcing of Southern Ocean biota by iron caused the initial approximately 40 p.p.m. of glacial-interglacial CO2 change, but other mechanisms must have accounted for the remaining 40 p.p.m. increase. The experiment also confirms that modest sequestration of atmospheric CO2 by artificial additions of iron to the Southern Ocean is in principle possible, although the period and geographical extent over which sequestration would be effective remain poorly known.     

Common variants in WFS1 confer risk of type 2 diabetes

We studied genes involved in pancreatic beta cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with diabetes risk. Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes.     

Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.     

基因工程为何必须坚持进行下去

今天的基因生物学充满了活力。它在有关细胞、酵母菌等单细胞生物以至复杂的人脑的生命科学中所占的份量与年俱增。这种奇妙的生物学热,在我最初踏人遗传学界时是完全无法想象的。1948年的生物学全是描述性的,处于科学标杆的最低部位,标杆的顶端是物理学。那时,爱因斯坦关于质．能互变的划时代理论已转化成为原子的巨大威力。如果不加约束的话,用它制成的武器完全可以摧毁人类文明的全部建筑物。因此,叙年代后期的物理学家们在因其使原子变成对社会有用之物而受人尊敬的同时,又担心他们发明的玩意儿一旦落入邪恶之手时,会干出何等蠢…