Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

Like phoenix from the ashes: How modern baleen whales arose from a fossil “dark age”

The evolution of baleen whales (Mysticeti), the largest animals on Earth, was punctuated by a pivotal turnover event. Following their emergence around 36 million years (Ma), mysticetes diversified into a disparate range of toothed and toothless species until 23 Ma, but then nearly vanished from the global fossil record for the next five million years. Following this early Miocene “dark age”, toothless mysticetes spectacularly reappeared around 18–17 Ma, whereas toothed mysticetes had gone entirely extinct. Here, we suggest that this turnover event reflects a change in mysticete habitat occupancy. Using the well-sampled record of Australasia as a case study, we show that Oligocene pre-“dark age” mysticetes formed distinct coastal and offshore assemblages, dominated by small (2–4 m), ecologically disparate toothed species, and larger (5–6 m) toothless filter feeders, respectively. Environmental change around the Oligocene–Miocene boundary led to the decline of the endemic coastal assemblages, leaving nearshore deposits virtually devoid of mysticetes. Filter feeders persisted offshore and subsequently re-invaded coastal habitats during the mid-Miocene Climatic Optimum, thus establishing the modern, cosmopolitan mysticete fauna

A Late Miocene potential neobalaenine mandible from Argentina sheds light on the origins of the living pygmy right whale

The origins and evolutionary relationships of the pygmy right whale (Caperea marginata), the only living member of the Neobalaeninae, have been the subject of a long-standing debate. This phylogenetic uncertainty is compounded by a limited neobalaenine fossil record. Here, we report a Late Miocene mysticete mandible from Patagonia, Argentina, and provisionally refer it to Neobalaeninae, gen. et sp. indet. The new material represents only the third report of a fossil neobalaenine, and the first fossil occurrence of this lineage in the southwestern Atlantic. It is also the oldest specimen so far reported, thus corroborating the idea of an early divergence time for neobalaenines

Raman spectroscopy of fossil bioapatite - A proxy for diagenetic alteration of the oxygen isotope composition

Fossil bioapatite may yield biogeochemical signals of paleoenvironments captured by living organisms. Bioapatite may be diagenetically altered, however, with ions added or removed post-mortem; such change is typically assessed using destructive and demanding techniques. Here, Raman spectroscopy is used as a rapid and non-destructive way to identify significant diagenetic alteration of fossil bioapatite. We found spectral parameters of phosphate symmetric stretching (μ1-PO43-) to be very sensitive to variations in apatite chemistry, particularly with respect to common diagenetic components (CO32-, F-, Sr2+). The Raman spectral parameters were subsequently applied to a set of modern (biogenic) and geologic (magmatic) apatite samples as potential endmembers for diagenetic alteration. Raman spectra were also collected from enamel and dentin (respectively resistant vs. alteration-prone) of fossil teeth. Phosphate-oxygen isotopic values from the same enamel-dentin samples were used as an index of alteration and provided definition of Raman spectral parameters as relates to diagenetic alteration. Diagenetically altered samples were characterised by spectra with μ1-PO43- widths (at half maximum height) less than 13.0cm-1, and μ1-PO43- band positions greater than 964.7cm-1. Raman spectroscopy is shown to have potential as a tool for pre-screening fossil apatite samples before further analyses. © 2011 Elsevier B.V.Articl

A bizarre new toothed mysticete (Cetacea) from Australia and the early evolution of baleen whales

Extant baleen whales (Cetacea, Mysticeti) are all large filter-feeding marine mammals that lack teeth as adults, instead possessing baleen, and feed on small marine animals in bulk. The early evolution of these superlative mammals, and their unique feeding method, has hitherto remained enigmatic. Here, I report a new toothed mysticete from the Late Oligocene of Australia that is more archaic than any previously described. Unlike all other mysticetes, this new whale was small, had enormous eyes and lacked derived adaptations for bulk filter-feeding. Several morphological features suggest that this mysticete was a macrophagous predator, being convergent on some Mesozoic marine reptiles and the extant leopard seal (Hydrurga leptonyx). It thus refutes the notions that all stem mysticetes were filter-feeders, and that the origins and initial radiation of mysticetes was linked to the evolution of filter-feeding. Mysticetes evidently radiated into a variety of disparate forms and feeding ecologies before the evolution of baleen or filter-feeding. The phylogenetic context of the new whale indicates that basal mysticetes were macrophagous predators that did not employ filter-feeding or echolocation, and that the evolution of characters associated with bulk filter-feeding was gradual

The Repronomics Project - enabling genetic improvement in reproduction in Northern Australia

This paper provides a brief description of a large breeding and genotyping project currently being conducted in northern Australia using three tropically-adapted beef breeds. Intensive recording of early-in-life female reproduction phenotypes using real-time ultrasound on large numbers of females will significantly increase the size of the genomic reference populations for these key traits and breeds. This phenotypic data, along with high density SNP genotypes, will provide crucial data to enable the effective implementation of new BREEDPLAN genomic evaluations currently being developed for the Australian beef industry, and will assist in increasing the accuracy of selection, especially in young bulls. The project design will also allow investigations of GxE interactions for female reproduction traits; the potential development of new traits; and methodologies required for the implementation of across-breed genomic evaluations

The Repronomics Project - enabling genetic improvement in reproduction in Northern Australia

This paper provides a brief description of a large breeding and genotyping project currently being conducted in northern Australia using three tropically-adapted beef breeds. Intensive recording of early-in-life female reproduction phenotypes using real-time ultrasound on large numbers of females will significantly increase the size of the genomic reference populations for these key traits and breeds. This phenotypic data, along with high density SNP genotypes, will provide crucial data to enable the effective implementation of new BREEDPLAN genomic evaluations currently being developed for the Australian beef industry, and will assist in increasing the accuracy of selection, especially in young bulls. The project design will also allow investigations of GxE interactions for female reproduction traits; the potential development of new traits; and methodologies required for the implementation of across-breed genomic evaluations