Whole-genome analysis informs breast cancer response to aromatase inhibition

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.     

Design, function and structure of a monomeric ClC transporter

Channels and transporters of the ClC family cause the transmembrane movement of inorganic anions in service of a variety of biological tasks, from the unusual-the generation of the kilowatt pulses with which electric fish stun their prey-to the quotidian-the acidification of endosomes, vacuoles and lysosomes. The homodimeric architecture of ClC proteins, initially inferred from single-molecule studies of an elasmobranch Cl(-) channel and later confirmed by crystal structures of bacterial Cl(-)/H(+) antiporters, is apparently universal. Moreover, the basic machinery that enables ion movement through these proteins-the aqueous pores for anion diffusion in the channels and the ion-coupling chambers that coordinate Cl(-) and H(+) antiport in the transporters-are contained wholly within each subunit of the homodimer. The near-normal function of a bacterial ClC transporter straitjacketed by covalent crosslinks across the dimer interface and the behaviour of a concatemeric human homologue argue that the transport cycle resides within each subunit and does not require rigid-body rearrangements between subunits. However, this evidence is only inferential, and because examples are known in which quaternary rearrangements of extramembrane ClC domains that contribute to dimerization modulate transport activity, we cannot declare as definitive a 'parallel-pathways' picture in which the homodimer consists of two single-subunit transporters operating independently. A strong prediction of such a view is that it should in principle be possible to obtain a monomeric ClC. Here we exploit the known structure of a ClC Cl(-)/H(+) exchanger, ClC-ec1 from Escherichia coli, to design mutants that destabilize the dimer interface while preserving both the structure and the transport function of individual subunits. The results demonstrate that the ClC subunit alone is the basic functional unit for transport and that cross-subunit interaction is not required for Cl(-)/H(+) exchange in ClC transporters.     

Development and longevity of ephemeral and perennial leaves on Artemisia tridentata Nutt. ssp. wyomingensis

Big sagebrush ( Artemisia tridentata Nutt.) is one of the most successful plants in the Great Basin based on its abundance and wide distribution. The development of dimorphic leaves may be an important mechanism attributing to its adaptive and competitive abilities. Development, persistence, and proportions of ephemeral and perennial leaves on Wyoming big sagebrush ( Artemisia tridentata Nutt. ssp. wyomingensis ) were studied for two years. The large ephemeral leaves are the first to develop in early spring. As early developing ephemerals mature and stems elongate, new ephemeral and perennial leaves develop in the axes of these large ephemerals. Perennial leaves expanded in the summer of their first growing season, persisting on the shrub until their abscission during summer drought of the second growing season. Plants maintained 33% of their leaf weight through the winters of 1985 and 1986. Active leaf and stem growth occurred at soil water potentials above –0.2 MPa.     

用CASI遥感数据估计横跨美国俄勒冈州针叶林叶面积指数

使用三类模型技术,对小型航空光谱制图成像仪(CASI)数据被用作估计针叶林叶面积指数(LAI)的潜力进行研究。三类技术为:单变量回归,多变量回归和植被指数(VI)基础的LAI估计模型。沿横跨美国俄勒冈州的各植被区选择四个研究立地,分别测定和收集LAI数据和CASI图像数据。CASI数据经校准后,研究其与LAI测定值的关系。结果说明二种成像方式的CASI数据对于LAI估计具有相似的效率。与其它两种技术比,逐步回归方法导致较高的LAI预测精度。在单变量回归和VI基础法中使用NDVI,比起其它形式的CASI数据能产生较好的效果。