Early Cambrian Arthropods from the Emu Bay Shale Lagerstatte, South Australia

© Instituto Geológico y Minero de España. The document attached has been archived with permission from the publisher.John R. Paterson, James B. Jago, James G. Gehling, Diego C. García-Bellido, Gregory D. Edgecombe and Michael S.Y. Le

A new vetulicolian from Australia and its bearing on the chordate affinities of an enigmatic Cambrian group

BACKGROUND: Vetulicolians are one of the most problematic and controversial Cambrian fossil groups, having been considered as arthropods, chordates, kinorhynchs, or their own phylum. Mounting evidence suggests that vetulicolians are deuterostomes, but affinities to crown-group phyla are unresolved. RESULTS: A new vetulicolian from the Emu Bay Shale Konservat-Lagerstätte, South Australia, Nesonektris aldridgei gen. et sp. nov., preserves an axial, rod-like structure in the posterior body region that resembles a notochord in its morphology and taphonomy, with notable similarity to early decay stages of the notochord of extant cephalochordates and vertebrates. Some of its features are also consistent with other structures, such as a gut or a coelomic cavity. CONCLUSIONS: Phylogenetic analyses resolve a monophyletic Vetulicolia as sister-group to tunicates (Urochordata) within crown Chordata, and this holds even if they are scored as unknown for all notochord characters. The hypothesis that the free-swimming vetulicolians are the nearest relatives of tunicates suggests that a perpetual free-living life cycle was primitive for tunicates. Characters of the common ancestor of Vetulicolia + Tunicata include distinct anterior and posterior body regions - the former being non-fusiform and used for filter feeding and the latter originally segmented - plus a terminal mouth, absence of pharyngeal bars, the notochord restricted to the posterior body region, and the gut extending to the end of the tail.Diego C García-Bellido, Michael S Y Lee, Gregory D Edgecombe, James B Jago, James G Gehling, and John R Paterso

Evidence of sensory-driven behavior in the Ediacaran organism Parvancorina: Implications and autecological interpretations

© 2017 International Association for Gondwana Research. Published by Elsevier B.V.. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (Dec 2017) in accordance with the publisher’s archiving policyThe ancient in situ fossil seafloor communities of the Ediacara biota present an unparalleled window into the assembly of the earliest complex macroscopic organisms, including early animals on Earth ca. 555 million years ago (mya). The unique preservation style of Ediacara fossil seafloors preserves whole communities virtually ‘frozen in time’, including both living and dead organisms at the time of burial. This phenomenon, where the fossilized organisms are arranged as they were in life offers an unparalleled opportunity to examine ecological patterns in some of the earliest examples of animal communities in deep time. The small, anchor-shaped fossil genus Parvancorina is common among the Ediacara biota; however, its morphology and ecology have received little attention. Here, we describe a population of juvenile Parvancorina preserved on a section of fossil seafloor recently excavated from the characteristic Ediacara Member from Ediacara Conservation Park in the Flinders Ranges, South Australia. We applied spatial methods to the sample population of Parvancorina (n = 202) and found that they demonstrated two size-clusters, distinguishing juveniles from adults, and further analyses showed that the smaller specimens tended to be spatially aggregated. For the first time among any Ediacara taxon, we found that this sample population of Parvancorina demonstrated a strong bimodal orientation, suggesting that orientation played an important behavioral role in its autecology. The aggregated spatial distribution and bimodal orientation of Parvancorina likely resulted from behavioral responses to the influence of benthic currents, suggesting that Parvancorina had a complex sensory network, and was capable of motility

Anatomical and ontogenetic reassessment of the Ediacaran frond Arborea arborea and its placement within total group Eumetazoa

Organisms in possession of a frondose body plan are amongst the oldest and most enigmatic members of the soft-bodied Ediacaran macrobiota. Appraisal of specimens from the late Ediacaran Ediacara Member of South Australia reveals that the frondose taxon Arborea arborea probably possessed a fluid-filled holdfast disc, the size and form of which could vary within populations. Mouldic preservation of internal anatomical features provides evidence for tissue differentiation, and for bundles of tubular structures within the stalk of the organism. These structures connect in a fascicled arrangement to individual lateral branches, before dividing further into individual units housed on those branches. The observed fascicled branching arrangement, which seemingly connects individual units to the main body of the organism, is consistent with a biologically modular construction for Arborea, and raises the possibility of a colonial organization. In conjunction with morphological characters previously recognized by other authors, including apical-basal and front-back differentiation, we propose that to the exclusion of all alternative known possibilities, Arborea can be resolved as a total group eumetazoan.This work was funded by the Natural Environment Research Council (GW4 DTP Studentship NE/L002434/1 to FSD, and Independent Research Fellowship NE/L011409/2 to AGL), and an Australian Research Council Discovery Grant (DP0453393) to JGG

Anatomical and ontogenetic reassessment of the Ediacaran frond Arborea arborea and its placement within total group Eumetazoa

Organisms in possession of a frondose body plan are amongst the oldest and most enigmatic members of the soft-bodied Ediacaran macrobiota. Appraisal of specimens from the late Ediacaran Ediacara Member of South Australia reveals that the frondose taxon Arborea arborea probably possessed a fluid-filled holdfast disc, the size and form of which could vary within populations. Mouldic preservation of internal anatomical features provides evidence for tissue differentiation, and for bundles of tubular structures within the stalk of the organism. These structures connect in a fascicled arrangement to individual lateral branches, before dividing further into individual units housed on those branches. The observed fascicled branching arrangement, which seemingly connects individual units to the main body of the organism, is consistent with a biologically modular construction for Arborea, and raises the possibility of a colonial organization. In conjunction with morphological characters previously recognized by other authors, including apical-basal and front-back differentiation, we propose that to the exclusion of all alternative known possibilities, Arborea can be resolved as a total group eumetazoan.This work was funded by the Natural Environment Research Council (GW4 DTP Studentship NE/L002434/1 to FSD, and Independent Research Fellowship NE/L011409/2 to AGL), and an Australian Research Council Discovery Grant (DP0453393) to JGG

STAT3 inhibition with Galiellalactone effectively targets the prostate cancer stem-like cell population."

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations

Reconstructing the reproductive mode of an Ediacaran macro-organism.

Enigmatic macrofossils of late Ediacaran age (580-541 million years ago) provide the oldest known record of diverse complex organisms on Earth, lying between the microbially dominated ecosystems of the Proterozoic and the Cambrian emergence of the modern biosphere. Among the oldest and most enigmatic of these macrofossils are the Rangeomorpha, a group characterized by modular, self-similar branching and a sessile benthic habit. Localized occurrences of large in situ fossilized rangeomorph populations allow fundamental aspects of their biology to be resolved using spatial point process techniques. Here we use such techniques to identify recurrent clustering patterns in the rangeomorph Fractofusus, revealing a complex life history of multigenerational, stolon-like asexual reproduction, interspersed with dispersal by waterborne propagules. Ecologically, such a habit would have allowed both for the rapid colonization of a localized area and for transport to new, previously uncolonized areas. The capacity of Fractofusus to derive adult morphology by two distinct reproductive modes documents the sophistication of its underlying developmental biology.This work has been supported by the Natural Environment Research Council [grant numbers NE/I005927/1 to C.G.K., NE/J5000045/1 to J.J.M., NE/L011409/1 to A.G.L. and NE/G523539/1 to E.G.M.], and a Henslow Junior Research Fellowship from Cambridge Philosophical Society to A.G.L.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nature1464

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

MRI Tracking of FePro Labeled Fresh and Cryopreserved Long Term In Vitro Expanded Human Cord Blood AC133+ Endothelial Progenitor Cells in Rat Glioma

Background: Endothelial progenitors cells (EPCs) are important for the development of cell therapies for various diseases. However, the major obstacles in developing such therapies are low quantities of EPCs that can be generated from the patient and the lack of adequate non-invasive imaging approach for in vivo monitoring of transplanted cells. The objective of this project was to determine the ability of cord blood (CB) AC133+ EPCs to differentiate, in vitro and in vivo, toward mature endothelial cells (ECs) after long term in vitro expansion and cryopreservation and to use magnetic resonance imaging (MRI) to assess the in vivo migratory potential of ex vivo expanded and cryopreserved CB AC133+ EPCs in an orthotopic glioma rat model. Materials, Methods and Results: The primary CB AC133+ EPC culture contained mainly EPCs and long term in vitro conditions facilitated the maintenance of these cells in a state of commitment toward endothelial lineage. At days 15–20 and 25–30 of the primary culture, the cells were labeled with FePro and cryopreserved for a few weeks. Cryopreserved cells were thawed and in vitro differentiated or IV administered to glioma bearing rats. Different groups of rats also received long-term cultured, magnetically labeled fresh EPCs and both groups of animals underwent MRI 7 days after IV administration of EPCs. Fluorescent microscopy showed that in vitro differentiation of EPCs was not affected by FePro labeling and cryopreservation. MRI analysis demonstrated that in vivo accumulation of previously cryopreserved transplanted cells resulted in significantly higher R2 and R2* values indicating a higher rate of migration and incorporation into tumor neovascularization of previously cryopreserved CB AC133+ EPCs to glioma sites, compared to non-cryopreserved cells. Conclusion: Magnetically labeled CB EPCs can be in vitro expanded and cryopreserved for future use as MRI probes for monitoring the migration and incorporation to the sites of neovascularization