Phylogeny of Acronychia (Rutaceae) and first insights into its historical biogeography and the evolution of fruit characters

Background: The genus Acronychia (Citrus family, Rutaceae) contains 49 species of trees and shrubs that are found mainly in rain forest. The genus has a large distributional range from mainland southern Asia to Australia and New Caledonia, but most species are endemic to either New Guinea or Australia. This study aimed to provide the first detailed molecular phylogeny of Acronychia and use it to test the taxonomic value of fruit morphological characters, and infer the historical biogeography of the genus.\ud \ud Methodology: Phylogenetic analyses (Bayesian Inference, Maximum Likelihood) were undertaken on nucleotide sequence data from two plastid (psbA-trnH, trnL-trnF) and three nuclear markers (ETS, ITS, NIAi3) from 29 Acronychia species (59% of the genus) and representatives of related genera.\ud \ud Results and Conclusions: The results indicate that the South-East Asian genus Maclurodendron is nested phylogenetically within Acronychia and must be synonymized to render Acronychia monophyletic. Fruit morphological characters have been used previously to infer relationships within Acronychia and our analyses show that these characters are informative for some subclades but are homoplasious for the group as a whole. Apocarpous fruits are the ancestral state in Acronychia and subapocarpous and fully syncarpous fruits are derived. The unisexual flowers of Maclurodendron are derived from bisexual flowers, which are found in all species of Acronychia as well as its relatives. Acronychia probably first evolved on Australia with range expansion to New Guinea via stepping-stone dispersal or direct land connections within the Sahul Shelf, followed by two independent dispersals to areas west of New Guinea. Most species of Acronychia occur in either Australia or New Guinea, but no species occurs in both regions. This is surprising given the close proximity of the landmasses, but might be explained by ecological factors

Phenotypic drift in metastatic progression of breast cancer: a case report with histologically heterogeneous lesions that are clonally related

Breast cancer metastasis to the stomach is rare; invasive lobular carcinoma has a predilection to spread to the gastrointestinal system and is morphologically similar to primary diffuse gastric carcinoma. This case highlights heterogeneous metastatic progression and that documentation of heterogeneity is important for informing future treatment strategies and prognostication

Phylogram of the 50% majority-rule consensus tree of the Bayesian analysis based on the ETS dataset.

<p>Posterior probability (PP) values of the Bayesian analysis and bootstrap values (BS) of the Garli analysis are displayed above the branches and unsupported nodes are marked with a hyphen (-). The voucher number is displayed after the species name for all taxa. The clade numbers refer to the clades from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136296#pone.0136296.g001" target="_blank">Fig 1</a>. <i>A</i> = <i>Acronychia</i>; <i>C</i> = <i>Comptonella</i>; <i>E</i> = <i>Euodia</i>; <i>M</i> = <i>Melicope</i>; <i>Ma</i> = <i>Maclurodendron</i>; <i>Me</i> = <i>Medicosma</i>; <i>T</i> = <i>Tetractomia</i>.</p

Voucher information and Genbank accession numbers for specimens used in the combined analyses.

<p>Herbarium acronyms are according to Index Herbariorum (<a href="http://sweetgum.nybg.org/ih/" target="_blank">http://sweetgum.nybg.org/ih/</a>). <i>A</i> = <i>Acronychia</i>; <i>C</i> = <i>Comptonella</i>; <i>E</i> = <i>Euodia</i>; <i>M</i> = <i>Melicope</i>; <i>Ma</i> = <i>Maclurodendron</i>; <i>Me</i> = <i>Medicosma</i>; <i>T</i> = <i>Tetractomia</i>. An asterisk (*) indicates sequences that were obtained in this study.</p

Ancestral area reconstruction in Mesquite based on the 50% majority-rule consensus tree of the Bayesian analysis of the concatenated data set (Fig 1).

<p>Voucher numbers are displayed after the species names for all taxa. <i>A</i> = <i>Acronychia</i>; <i>C</i> = <i>Comptonella</i>; <i>E</i> = <i>Euodia</i>; <i>M</i> = <i>Melicope</i>; <i>Ma</i> = <i>Maclurodendron</i>; <i>Me</i> = <i>Medicosma</i>; <i>T</i> = <i>Tetractomia</i>.</p

Voucher information and Genbank accession numbers for specimens additionally used for the separate ETS and ITS analyses.

<p>Herbarium acronyms are according to Index Herbariorum (<a href="http://sweetgum.nybg.org/ih/" target="_blank">http://sweetgum.nybg.org/ih/</a>). <i>A</i> = <i>Acronychia</i>. An asterisk (*) indicates sequences that were obtained in this study.</p

Fruit characters plotted on the 50% majority-rule consensus tree of the Bayesian analysis of the concatenated data set (Fig 1).

<p>The left tree contains the information about the fusion of carpels whereas the right tree shows the characters states for mesocarp texture. The voucher number is displayed after the species name for all taxa. Drawings by M. Appelhans (1–3) and Donald Fortesque (reprinted with permission from CSIRO). <i>A</i> = <i>Acronychia</i>; <i>C</i> = <i>Comptonella</i>; <i>E</i> = <i>Euodia</i>; <i>M</i> = <i>Melicope</i>; <i>Ma</i> = <i>Maclurodendron</i>; <i>Me</i> = <i>Medicosma</i>; <i>T</i> = <i>Tetractomia</i>.</p

Models of sequence evolution estimated using the Bayesian Information Criterion (BIC) algorithm in jModeltest 2.1.3.

<p>The table shows the models with the highest likelihood scores and the highest available models that are available in the programs MrBayes and Garli.</p

Metastatic progression of breast cancer: Insights from 50 years of autopsies

There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment and pathological aspects of all cases and, additionally, pathological features and biomarker expression (ER, PgR, HER2, EGFR, p53, Ki67, c-Kit, CK AE1/AE3) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analysed by array-based comparative genomic hybridization for six cases##. 945 metastatic deposits were identified, with a median of four/patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%) and non-axillary lymph nodes (55%). Major findings included: (a) patients with CNS metastases were more likely to have bone metastases (p < 0.013); (b) younger age was associated with metastasis to the liver (≤ 49 years; p < 0.001) and to gynaecological organs (≤ 49 years; p = 0.001); (c) surgical excision of the primary tumour was associated with metastasis to the liver (p = 0.002); and (d) ER and PgR showed down-regulation during progression in a non-random manner, particularly in lung/pleura (ER; p < 0.001), liver and bone metastases. Genomic analysis revealed DNA copy number variation between the primary tumour and metastases (e.g. amplification of 2q11.2-q12.1 and 10q22.2-q22.3) but little variation between metastases from the same patient. In summary, the association of CNS and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for the management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies