Hemorrhage associated with hepatic artery pseudoaneurysms after regional chemotherapy with floxuridine: case report

Pseudoaneurysms of the hepatic artery are a rare complication in patients with primary or secondary liver tumors treated with intra-arterial chemotherapy. We present two patients who developed this complication after placement of a catheter system into the gastroduodenal artery and initiation of regional chemotherapy with floxuridine. Diagnosis was made after symptomatic bleeding occurred, necessitating emergency angiography with coil embolization. Pseudoaneurysms usually occur after mechanical damage of the vessel wall, but the chemical toxicity of floxuridine may add to the development of vascular impairment

Universal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution

Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Template-directed replication of informational polymers, which takes place during the dehydration stage of each cycle, is considered to be sequence-independent. New sequences are generated by spontaneous polymer formation, and all sequences compete for a finite monomer resource that is recycled via reversible polymerization. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer/polymer diffusivities

Relative sea-level rise around East Antarctica during Oligocene glaciation

During the middle and late Eocene (∼48-34 Myr ago), the Earth's climate cooled and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarcticainduced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rosedespite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line

Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity

BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of \u3b3-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL

Dynamic behaviour of the East Antarctic ice sheet during Pliocene warmth

Warm intervals within the Pliocene epoch (5.33–2.58 million years ago) were characterized by global temperatures comparable to those predicted for the end of this century1 and atmospheric CO2 concentrations similar to today2, 3, 4. Estimates for global sea level highstands during these times5 imply possible retreat of the East Antarctic ice sheet, but ice-proximal evidence from the Antarctic margin is scarce. Here we present new data from Pliocene marine sediments recovered offshore of Adélie Land, East Antarctica, that reveal dynamic behaviour of the East Antarctic ice sheet in the vicinity of the low-lying Wilkes Subglacial Basin during times of past climatic warmth. Sedimentary sequences deposited between 5.3 and 3.3 million years ago indicate increases in Southern Ocean surface water productivity, associated with elevated circum-Antarctic temperatures. The geochemical provenance of detrital material deposited during these warm intervals suggests active erosion of continental bedrock from within the Wilkes Subglacial Basin, an area today buried beneath the East Antarctic ice sheet. We interpret this erosion to be associated with retreat of the ice sheet margin several hundreds of kilometres inland and conclude that the East Antarctic ice sheet was sensitive to climatic warmth during the Pliocene