Late Triassic (Rhaetian) conodonts and ichthyoliths from Chile

The Late Triassic of the back arc Domeyko Basin, Chile is characterized by the onset of marine sedimentation that persisted throughout the rest of the Mesozoic. Carbonate bulk samples from the Punta del Viento Limestone Formation have yielded a numerically small, but apparently widespread, conodont fauna including Epigondolella mosheri, Epigondolella englandi and Neogondolella steinbergensis. These specimens indicate a Rhaetian (Epigondolella mosheri conodont Biozone roughly equivalent to the Paracochloceras amoenum ammonoid Biozone) age for this unit. Their recovery represents the first record of conodonts from Chile, and also indicates a considerable potential for use in correlating sequence stratigraphic events within the Mesozoic Marginal Sea in Colombia, Peru and Chile

Dust effects on the derived Sersic indexes of disks and bulges in spiral galaxies

We present a theoretical study that quantifies the effect of dust on the derived Sersic indexes of disks and bulges. The changes in the derived parameters from their intrinsic values (as seen in the absence of dust) were obtained by fitting Sersic distributions on simulated images of disks and bulges produced using radiative transfer calculations and the model of Popescu et al. 2011. We found that dust has the effect of lowering the measured Sersic index in most cases, with stronger effects for disks and bulges seen through more optically thick lines of sight.Comment: 3 pages, 2 figures, to appear in the Proceedings of the IAU Symposium No.284, "The Spectral Energy Distribution of Galaxies", 5-9 sept. 2011, editors Richard J. Tuffs and Cristina C. Popesc

The nearshore cradle of early vertebrate diversification

Ancestral vertebrate habitats are subject to controversy and obscured by limited, often contradictory paleontological data. We assembled fossil vertebrate occurrence and habitat datasets spanning the middle Paleozoic (480 million to 360 million years ago) and found that early vertebrate clades, both jawed and jawless, originated in restricted, shallow intertidal-subtidal environments. Nearshore divergences gave rise to body plans with different dispersal abilities: Robust fishes shifted shoreward, whereas gracile groups moved seaward. Fresh waters were invaded repeatedly, but movement to deeper waters was contingent upon form and short-lived until the later Devonian. Our results contrast with the onshore-offshore trends, reef-centered diversification, and mid-shelf clustering observed for benthic invertebrates. Nearshore origins for vertebrates may be linked to the demands of their mobility and may have influenced the structure of their early fossil record and diversification

Calcium signalling links MYC to NUAK1

NUAK1 is a member of the AMPK-related family of kinases. Recent evidence suggests that NUAK1 is an important regulator of cell adhesion and migration, cellular and organismal metabolism, and regulation of TAU stability. As such, NUAK1 may play key roles in multiple diseases ranging from neurodegeneration to diabetes and metastatic cancer. Previous work revealed a crucial role for NUAK1 in supporting viability of tumour cells specifically when MYC is overexpressed. This role is surprising, given that NUAK1 is activated by the tumour suppressor LKB1. Here we show that, in tumour cells lacking LKB1, NUAK1 activity is maintained by an alternative pathway involving calcium-dependent activation of PKCα. Calcium/PKCα-dependent activation of NUAK1 supports engagement of the AMPK-TORC1 metabolic checkpoint, thereby protecting tumour cells from MYC-driven cell death, and indeed, MYC selects for this pathway in part via transcriptional regulation of PKCα and ITPR. Our data point to a novel role for calcium in supporting tumour cell viability and clarify the synthetic lethal interaction between NUAK1 and MYC

MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in both gain-of-function TP53 mutations and metastasis, but this has not been fully explored in PDAC. Here we set out to identify miRNAs which are specifically dysregulated in metastatic PDAC. To achieve this, we utilised established mouse models of PDAC to profile miRNA expression in primary tumours expressing the metastasis-inducing mutant p53R172H and compared these to two control models carrying mutations, which promote tumour progression but do not induce metastasis. We show that a subset of miRNAs are dysregulated in mouse PDAC tumour tissues expressing mutant p53R172H, primary cell lines derived from mice with the same mutations and in TP53 null cells with ectopic expression of the orthologous human mutation, p53R175H. Specifically, miR-142-3p is downregulated in all of these experimental models. We found that DNA methyltransferase 1 (Dnmt1) is upregulated in tumour tissue and cell lines, which express p53R172H. Inhibition or depletion of Dnmt1 restores miR-142-3p expression. Overexpression of miR-142-3p attenuates the invasive capacity of p53R172H-expressing tumour cells. MiR-142-3p dysregulation is known to be associated with cancer progression, metastasis and the miRNA is downregulated in patients with PDAC. Here we link TP53 gain-of-function mutations to Dnmt1 expression and in turn miR-142-3p expression. Additionally, we show a correlation between expression of these genes and patient survival, suggesting that they may have potential to be therapeutic targets

c-Src drives intestinal regeneration and transformation

The non‐receptor tyrosine kinase c‐Src, hereafter referred to as Src, is overexpressed or activated in multiple human malignancies. There has been much speculation about the functional role of Src in colorectal cancer (CRC), with Src amplification and potential activating mutations in up to 20% of the human tumours, although this has never been addressed due to multiple redundant family members. Here, we have used the adult <i>Drosophila</i> and mouse intestinal epithelium as paradigms to define a role for Src during tissue homeostasis, damage‐induced regeneration and hyperplasia. Through genetic gain and loss of function experiments, we demonstrate that Src is necessary and sufficient to drive intestinal stem cell (ISC) proliferation during tissue self‐renewal, regeneration and tumourigenesis. Surprisingly, Src plays a non‐redundant role in the mouse intestine, which cannot be substituted by the other family kinases Fyn and Yes. Mechanistically, we show that Src drives ISC proliferation through upregulation of EGFR and activation of Ras/MAPK and Stat3 signalling. Therefore, we demonstrate a novel essential role for Src in intestinal stem/progenitor cell proliferation and tumourigenesis initiation <i>in vivo.</i&gt

Loss of TGF-β signaling drives cSCC from skin stem cells:more evidence

No abstract available

Discriminating signal from noise in the fossil record of early vertebrates reveals cryptic evolutionary history

The fossil record of early vertebrates has been influential in elucidating the evolutionary assembly of the gnathostome bodyplan. Understanding of the timing and tempo of vertebrate innovations remains, however, mired in a literal reading of the fossil record. Early jawless vertebrates (ostracoderms) exhibit restriction to shallow-water environments. The distribution of their stratigraphic occurrences therefore reflects not only flux in diversity, but also secular variation in facies representation of the rock record. Using stratigraphic, phylogenetic and palaeoenvironmental data, we assessed the veracity of the fossil records of the jawless relatives of jawed vertebrates (Osteostraci, Galeaspida, Thelodonti, Heterostraci). Non-random models of fossil recovery potential using Palaeozoic sea-level changes were used to calculate confidence intervals of clade origins. These intervals extend the timescale for possible origins into the Upper Ordovician; these estimates ameliorate the long ghost lineages inferred for Osteostraci, Galeaspida and Heterostraci, given their known stratigraphic occurrences and stem–gnathostome phylogeny. Diversity changes through the Silurian and Devonian were found to lie within the expected limits predicted from estimates of fossil record quality indicating that it is geological, rather than biological factors, that are responsible for shifts in diversity. Environmental restriction also appears to belie ostracoderm extinction and demise rather than competition with jawed vertebrates