Globular fossils showing palintomic cell cleavage in the Ediacaran Doushantuo Formation, China, are widely regarded as embryos of early metazoans, although metazoan synapomorphies, tissue ...differentiation, and associated juveniles or adults are lacking. We demonstrate using synchrotron-based x-ray tomographic microscopy that the fossils have features incompatible with multicellular metazoan embryos. The developmental pattern is comparable with nonmetazoan holozoans, including germination stages that preclude postcleavage embryology characteristic of metazoans. We conclude that these fossils are neither animals nor embryos. They belong outside crown-group Metazoa, within total-group Holozoa (the sister clade to Fungi that includes Metazoa, Choanoflagellata, and Mesomycetozoea) or perhaps on even more distant branches in the eukaryote tree. They represent an evolutionary grade in which palintomic cleavage served the function of producing propagules for dispersion.
A virtual world of paleontology Cunningham, John A.; Rahman, Imran A.; Lautenschlager, Stephan ...
Trends in ecology & evolution,
06/2014, Letnik:
29, Številka:
6
Journal Article
Recenzirano
Odprti dostop
•Computer-aided visualization and analysis has revolutionized the study of fossils.•Fossils can now be characterized in three dimensions and in unprecedented detail.•The resulting digital ...reconstructions can be used in rigorous functional analyses.•Hypotheses regarding the function of extinct organisms can therefore be tested.
Computer-aided visualization and analysis of fossils has revolutionized the study of extinct organisms. Novel techniques allow fossils to be characterized in three dimensions and in unprecedented detail. This has enabled paleontologists to gain important insights into their anatomy, development, and preservation. New protocols allow more objective reconstructions of fossil organisms, including soft tissues, from incomplete remains. The resulting digital reconstructions can be used in functional analyses, rigorously testing long-standing hypotheses regarding the paleobiology of extinct organisms. These approaches are transforming our understanding of long-studied fossil groups, and of the narratives of organismal and ecological evolution that have been built upon them.
Exceptionally preserved fossils provide major insights into the evolutionary history of life. Microbial activity is thought to play a pivotal role in both the decay of organisms and the preservation ...of soft tissue in the fossil record, though this has been the subject of very little experimental investigation. To remedy this, we undertook an experimental study of the decay of the brine shrimp Artemia, examining the roles of autolysis, microbial activity, oxygen diffusion and reducing conditions. Our findings indicate that endogenous gut bacteria are the main factor controlling decay. Following gut wall rupture, but prior to cuticle failure, gut-derived microbes spread into the body cavity, consuming tissues and forming biofilms capable of mediating authigenic mineralization, that pseudomorph tissues and structures such as limbs and the haemocoel. These observations explain patterns observed in exceptionally preserved fossil arthropods. For example, guts are preserved relatively frequently, while preservation of other internal anatomy is rare. They also suggest that gut-derived microbes play a key role in the preservation of internal anatomy and that differential preservation between exceptional deposits might be because of factors that control autolysis and microbial activity. The findings also suggest that the evolution of a through gut and its bacterial microflora increased the potential for exceptional fossil preservation in bilaterians, providing one explanation for the extreme rarity of internal preservation in those animals that lack a through gut.
To compare functional and anatomical outcomes, rates of culture positivity and number of procedures in eyes with endophthalmitis following phacoemulsification surgery, treated with either primary ...vitrectomy and intravitreal antibiotics or vitreous tap and antibiotic injection (T&I).
Patients developing endophthalmitis after phacoemulsification surgery between 2007 and 2016 were identified, and outcomes were compared between the two treatment groups.
19 patients underwent a primary vitrectomy and 22 underwent a T&I. There was a significant improvement in visual acuity after T&I (p=.003) and primary vitrectomy (p=.00005). The median improvement in visual acuity was significantly greater for the primary vitrectomy group than the T&I group (p=.024). 64% of eyes were culture positive with the initial T&I, and 63% with primary vitrectomy (p=1.00). Two eyes initially culture negative with a T&I, and three eyes that were culture positive with a T&I were subsequently culture positive with a vitrectomy 24-72 hours later. 68% of patients who underwent a T&I required an additional procedure, compared to 26% of the vitrectomy group (p=.01). The T&I group underwent a mean of 2.3 procedures each, and the primary vitrectomy group underwent 1.5 (p=.03).
Eyes with endophthalmitis treated with a primary vitrectomy demonstrated greater visual improvement and needed fewer procedures than those initially treated with a T&I. Viable bacteria were only seen in subsequent procedures in the T&I group, indicating that primary vitrectomy was superior at sterilizing the eye.
Early Cambrian Pseudooides prima has been described from embryonic and post-embryonic stages of development, exhibiting long germ-band development. There has been some debate about the pattern of ...segmentation, but this interpretation, as among the earliest records of ecdysozoans, has been generally accepted. Here, we show that the ‘germ band’ of P. prima embryos separates along its mid axis during development, with the transverse furrows between the ‘somites’ unfolding into the polar aperture of the ten-sided theca of Hexaconularia sichuanensis, conventionally interpreted as a scyphozoan cnidarian; co-occurring post-embryonic remains of ecdysozoans are unrelated. We recognize H. sichuanensis as a junior synonym of P. prima as a consequence of identifying these two form-taxa as distinct developmental stages of the same organism. Direct development in P. prima parallels the co-occuring olivooids Olivooides, and Quadrapyrgites and Bayesian phylogenetic analysis of a novel phenotype dataset indicates that, despite differences in their tetra-, penta- and pseudo-hexa-radial symmetry, these hexangulaconulariids comprise a clade of scyphozoan medusozoans, with Arthrochites and conulariids, that all exhibit direct development from embryo to thecate polyp. The affinity of hexangulaconulariids and olivooids to extant scyphozoan medusozoans indicates that the prevalence of tetraradial symmetry and indirect development are a vestige of a broader spectrum of body-plan symmetries and developmental modes that was manifest in their early Phanerozoic counterparts.
Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus ...predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels. Zinc interferes with IFN-λ3 binding to IFNL receptor 1 (IFNLR1), resulting in decreased antiviral activity and increased viral replication (HCV, influenza) in vitro. HCV patients with high zinc levels have low hepatocyte antiviral and inflammatory gene expression and high viral loads, confirming the inhibitory role of zinc in vivo. We provide the first evidence that zinc can act as a potent and specific inhibitor of IFN-λ3 signalling and highlight its potential as a target of therapeutic intervention for IFN-λ3-mediated chronic disease.
Fossilized embryos from the late Neoproterozoic and earliest Phanerozoic have caused much excitement because they preserve the earliest stages of embryology of animals that represent the initial ...diversification of metazoans. However, the potential of this material has not been fully realized because of reliance on traditional, non-destructive methods that allow analysis of exposed surfaces only, and destructive methods that preserve only a single two-dimensional view of the interior of the specimen. Here, we have applied synchrotron-radiation X-ray tomographic microscopy (SRXTM), obtaining complete three-dimensional recordings at submicrometre resolution. The embryos are preserved by early diagenetic impregnation and encrustation with calcium phosphate, and differences in X-ray attenuation provide information about the distribution of these two diagenetic phases. Three-dimensional visualization of blastomere arrangement and diagenetic cement in cleavage embryos resolves outstanding questions about their nature, including the identity of the columnar blastomeres. The anterior and posterior anatomy of embryos of the bilaterian worm-like Markuelia confirms its position as a scalidophoran, providing new insights into body-plan assembly among constituent phyla. The structure of the developing germ band in another bilaterian, Pseudooides, indicates a unique mode of germ-band development. SRXTM provides a method of non-invasive analysis that rivals the resolution achieved even by destructive methods, probing the very limits of fossilization and providing insight into embryology during the emergence of metazoan phyla.
Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients ...with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo.
We did a multicentre, randomised, placebo-controlled, phase 3 trial (TACE 2) in 20 hospitals in the UK for patients with unresectable, liver-confined hepatocellular carcinoma. Patients were eligible if they were at least aged 18 years, had Eastern Cooperative Oncology Group performance status of 1 or less, and had Child-Pugh A liver disease. Patients were randomised 1:1 by computerised minimisation algorithm to continuous oral sorafenib (400 mg twice-daily) or matching placebo combined with TACE using drug-eluting beads (DEB-TACE), which was given via the hepatic artery 2–5 weeks after randomisation and according to radiological response and patient tolerance thereafter. Patients were stratified according to randomising centre and serum α-fetoprotein concentration (<400 ng/mL and ≥400 ng/mL). Only the trial coordinator was unmasked to treatment allocation before patient progression during the study. The primary endpoint was progression-free survival defined as the interval between randomisation and progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) or death due to any cause, and was analysed by intention-to-treat. Safety was analysed by intention-to-treat. The trial has been completed and the final results are reported. The trial is registered at EudraCT, number 2008-005073-36, and ISRCTN, number ISRCTN93375053.
Between Nov 4, 2010, and Dec 7, 2015, the trial enrolled 399 patients and was terminated after a planned interim futility analysis. 86 patients failed screening and 313 remaining patients were randomly assigned: 157 to sorafenib and 156 to placebo. The median daily dose was 660 mg (IQR 389·2–800·0) sorafenib versus 800 mg (758·2–800·0) placebo, and median duration of therapy was 120·0 days (IQR 43·0–266·0) for sorafenib versus 162·0 days (70·0–323·5) for placebo. There was no evidence of difference in progression-free survival between the sorafenib group and the placebo group (hazard ratio HR 0·99 95% CI 0·77–1·27, p=0·94); median progression-free survival was 238·0 days (95% CI 221·0–281·0) in the sorafenib group and 235·0 days (209·0–322·0) in the placebo group. The most common grade 3–4 adverse events were fatigue (29 18% of 157 patients in the sorafenib group vs 21 13% of 156 patients in the placebo group), abdominal pain (20 13% vs 12 8%), diarrhoea (16 10% vs four 3%), gastrointestinal disorders (18 11% vs 12 8%), and hand–foot skin reaction (12 8% and none). At least one serious adverse event was reported in 65 (41%) of 157 patients in the sorafenib group and 50 (32%) of 156 in the placebo group, and 181 serious adverse events were reported in total, 95 (52%) in the sorafenib group and 86 (48%) in the placebo group. Three deaths occurred in each group that were attributed to DEB-TACE. Four deaths were attributed to study drug; three in the sorafenib group and one in the placebo group.
The addition of sorafenib to DEB-TACE does not improve progression-free survival in European patients with hepatocellular carcinoma. Alternative systemic therapies need to be assessed in combination with TACE to improve patient outcomes.
Bayer PLC and BTG PLC.
Tiananmen moon Cunningham, Philip J
2014., 2014, 2014-05-05
eBook
This compelling book provides a vivid firsthand account of the student demonstrations and massacre in Tiananmen Square in 1989. Uniquely placed as a Western observer drawn into active participation ...through Chinese friends in the uprising, Philip J Cunningham offers a remarkable day-by-day account of Beijing students desperately trying to secure the most coveted political real estate in China in the face of ever-more daunting government countermoves. Tiananmen Moon takes the reader into the thick of the 1989 protests while also following the parallel response of an unprepared but resourceful Western media. In this revised and expanded edition, Cunningham recounts rare vignettes about life in Tiananmen Square under student leadership, including previously unpublished material. There is an account of the Goddess of Democracy being unveiled, a whimsical trip to the countryside that ends up on a collision course with PLA troops readying for attack, the tale of a near riot when a reporter is mistaken for Gorbachev, the saga of a tearful leader who quits and dictates her last will and testament to the author, and a dramatic account of futile resistance in the face of an unforgiving crackdown. The book chronicles the opportunistic and awkward tango between naive student activists and jaded foreign journalists, in which, after a month of mutual courting, the tables turn and the now-savvy students watch the journalists, seduced and confused, run circles just trying to keep up. During the hunger strike under the light of a full moon, China bares its conflicted soul to the world, the mournful cry for reform amplified by the footsteps of a million peaceful marchers. This remarkable testament to a searing month that changed China forever serves as a witness to the rise and fall of an uprising, capturing the plaintive and lyrical beauty of a dream that endures and continues to haunt the country today.
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