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Endocrine therapy has become one of most effective forms of targeted adjuvant therapy for hormone-sensitive breast cancer and may be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor downregulators. Tumor cells can develop resistance to endocrine therapy, a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptors and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, resistance to this therapy is thought to be a progressive, step-wise process, and the underlying mechanism remains unclear. In this review, we summarize the possible biological and molecular mechanisms that underlie endocrine resistance, and discuss some novel strategies to overcoming these issues.

Nearly half of the species in the large genus Saxifraga belong to Saxifraga sect. Ciliatae, a largely Sino‐Himalayan taxon. We report here that evidence from chloroplast DNA sequences (psbA‐trnH, trnL‐F) and from nuclear sequences (ITS) indicates that this section is monophyletic and composed of at least three main lineages, corresponding to (1) a clade made up of species from S. subsect. Gemmiparae, subsect. Cinerascentes, subsect. Flagellares and subsect. Hemisphaericae, in which the last three subsections are nested in the first; (2) a clade of species belonging to S. subsect. Rosulares (including S. subsect. Serpyllifoliae); and (3) a clade of species belonging to S. subsect. Hirculoideae. Species relationships in S. subsect. Rosulares and subsect. Hirculoideae are not well resolved. A molecular clock analysis indicates that the diversification of S. sect. Ciliatae into its three lineages dates from ca. 9.48 Ma, coinciding with orogenic events associated with one of the most important phases of uplift of the Qinghai‐Tibet Plateau. Extensive diversifications within S. subsect. Rosulares and subsect. Hirculoideae have been more recent (ca. 4.51 Ma and 2.12 Ma, respectively), again correlated with Qinghai‐Tibet Plateau uplift events and, in the case of S. subsect. Hirculoideae, have occurred at a rate comparable to that seen in the radiation of Hawaiian fruit flies.

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In the present study, we used two maternally inherited plastid DNA intergenic spacers, rpl20-rps12 and trnS-trnG, and the biparentally inherited nuclear ribosomal internal transcribed spacer (ITS) region to explore genetic variation and phylogeographical history of Rhodiola alsia, a herb endemic to the Qinghai-Tibetan Plateau (QTP). Based on range-wide sampling (18 populations and 227 individuals), we detected 45 plastid DNA haplotypes and 19 ITS sequence types. Only three plastid DNA haplotypes were widespread; most haplotypes were restricted to single sites or to neighbouring populations. Analysis of molecular variance revealed that most of the genetic variance was found within populations (51.24%) but that populations were also distinct (FST = 0.48759). We found three areas with relatively high plastid DNA diversity and these could further be recognized as potentially isolated divergence centres based on the ITS sequence type distribution. These represent three potentially isolated glacial refugia for R. alsia: one of them has long been recognized as an important refugium on the south-eastern edge of the QTP, whereas the others are new and located in the north and south of the Tanggula Mountains on the plateau platform. Divergence time estimates based on ITS suggest that the main lineages of R. alsia diverged from each other 0.35-0.87 Mya, indicating that climatic oscillations during the Pleistocene may have been an important driver of intraspecific divergence in R. alsia. Rhodiola alsia probably experienced a phylogeographical history of retreat to isolated glacial refugia during Quaternary glaciations that led to different degrees of allopatric intraspecific divergence.

Sperm competition is a major force in sexual selection, but its implications for mating-system and life-history evolution are only beginning to be understood. The well-known sneak^guard model predicts that sneaks will win in sperm competition. We now provide empirical con¢rmation of this prediction. Bluegill sun¢sh (Lepomis macrochirus) have both sneak (cuckolder) and guard (parental) males. Guards make nests, court females and provide solitary parental care for the embryos. Sneaks include small cuckolders, which are termed`sneakers', that dart in and out of nests in order to ejaculate between the spawning pair and larger cuckolders, which are termed`satellites', that mimic females in order to ejaculate between the spawning pair. Using ¢eld behavioural data, genetic data and new mathematical models for paternity analyses, we show, for the ¢rst time to the authors' knowledge, that sneaks fertilize more eggs than guards during sperm competition. In addition, we show that sneakers are superior to satellites in sperm competition and, thus, that even among sneaks there are tactic-speci¢c di¡erences in competitive success.

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BackgroundThe chloroplast (cp) genome is useful in plant systematics, genetic diversity analysis, molecular identification and divergence dating. The genus Gentiana contains 362 species, but there are only two valuable complete cp genomes. The purpose of this study is to report the characterization of complete cp genome of G. lawrencei var. farreri, which is endemic to the Qinghai-Tibetan Plateau (QTP).MethodsUsing high throughput sequencing technology, we got the complete nucleotide sequence of the G. lawrencei var. farreri cp genome. The comparison analysis including genome difference and gene divergence was performed with its congeneric species G. straminea. The simple sequence repeats (SSRs) and phylogenetics were studied as well.ResultsThe cp genome of G. lawrencei var. farreri is a circular molecule of 138,750 bp, containing a pair of 24,653 bp inverted repeats which are separated by small and large single-copy regions of 11,365 and 78,082 bp, respectively. The cp genome contains 130 known genes, including 85 protein coding genes (PCGs), eight ribosomal RNA genes and 37 tRNA genes. Comparative analyses indicated that G. lawrencei var. farreri is 10,241 bp shorter than its congeneric species G. straminea. Four large gaps were detected that are responsible for 85% of the total sequence loss. Further detailed analyses revealed that 10 PCGs were included in the four gaps that encode nine NADH dehydrogenase subunits. The cp gene content, order and orientation are similar to those of its congeneric species, but with some variation among the PCGs. Three genes, ndhB, ndhF and clpP, have high nonsynonymous to synonymous values. There are 34 SSRs in the G. lawrencei var. farreri cp genome, of which 25 are mononucleotide repeats: no dinucleotide repeats were detected. Comparison with the G. straminea cp genome indicated that five SSRs have length polymorphisms and 23 SSRs are species-specific. The phylogenetic analysis of 48 PCGs from 12 Gentianales taxa cp genomes clearly identified three clades, which indicated the potential of cp genomes in phylogenetics.DiscussionThe “missing” sequence of G. lawrencei var. farreri mainly consistent of ndh genes which could be dispensable under chilling-stressed conditions in the QTP. The complete cp genome sequence of G. lawrencei var. farreri provides intragenic information that will contribute to genetic and phylogenetic research in the Gentianaceae.