Ruptured Internal Iliac Artery Aneurysm: Staged Emergency Endovascular Treatment in the Interventional Radiology Suite

Ruptured aneurysms of the internal iliac artery (IIA) are rare and challenging to treat surgically. Due to their anatomic location they are difficult to operate on and perioperative morbidity is high. An endovascular approach can be helpful. We recently treated a patient with a ruptured IIA aneurysm in the interventional radiology suite with embolization of the side-branch of the IIA and placement of a covered stent in the ipsilateral common and external iliac arteries. A suitable stent-graft was not available initially and had to be brought in from elsewhere. An angioplasty balloon was temporarily placed across the ostium of the IIA to obtain hemostasis. Two hours later, the procedure was finished by placing the stent-graft

RNA-directed activation of cytoplasmic ayriein-1 in reconstituted transport RNPs

Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the regulation of their movement are poorly understood. We have reconstituted microtubule minus end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a cis-acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport

Ordered arrays of multiferroic epitaxial nanostructures

Epitaxial heterostructures combining ferroelectric (FE) and ferromagnetic (FiM) oxides are a possible route to explore coupling mechanisms between the two independent order parameters, polarization and magnetization of the component phases. We report on the fabrication and properties of arrays of hybrid epitaxial nanostructures of FiM NiFe2O4 (NFO) and FE PbZr0.52Ti0.48O3 or PbZr0.2Ti0.8O3, with large range order and lateral dimensions from 200 nm to 1 micron

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes, and as such may be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.Comment: 9 pages, 2 Figures, 1 Table, 2 boxes, Trends in Biochemical Sciences 2010 October issue cover stor

Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors

Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. However, interpretation of these data is problematical because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its preferred targets, it does show relatively low overall kinase selectivity. Several lines of data support a role for both p38 and JNK1/2 activation in the control of cellular proliferation and also the pathology of diseases of ageing, including type II diabetes, diseases to which Werner Syndrome individuals are prone, thus making the use of JNK inhibitors attractive as possible therapeutics. We have thus tested the effects of the widely used JNK inhibitor SP600125 on the proliferation and morphology of WS cells. In addition we synthesised and tested two recently described aminopyridine based inhibitors. SP600125 treatment resulted in the cessation of proliferation of WS cells and resulted in a senescent-like cellular phenotype that does not appear to be related to the inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD 6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular proliferation of immortalised WS cells, but no effect on the replicative lifespan of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially explain its effects on WS cells, since MK2 is known to be involved in regulating cellular morphology via HSP27 phosphorylation, and is thought to play a role in cell cycle arrest. These data suggest that total JNK1/2 activity does not play a substantial role in the proliferation control in WS cells

The Molecular Chaperone Hsp90α Is Required for Meiotic Progression of Spermatocytes beyond Pachytene in the Mouse

The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast to Drosophila. In mammals, two genes encode the two highly similar and functionally largely redundant isoforms Hsp90α and Hsp90β. Although they are co-expressed in most if not all cells, their relative levels vary between tissues and during development. Since mouse embryos lacking Hsp90β die at implantation, and despite the fact that Hsp90 inhibitors being tested as anti-cancer agents are relatively well tolerated, the organismic functions of Hsp90 in mammals remain largely unknown. We have generated mouse lines carrying gene trap insertions in the Hsp90α gene to investigate the global functions of this isoform. Surprisingly, mice without Hsp90α are apparently normal, with one major exception. Mutant male mice, whose Hsp90β levels are unchanged, are sterile because of a complete failure to produce sperm. While the development of the male reproductive system appears to be normal, spermatogenesis arrests specifically at the pachytene stage of meiosis I. Over time, the number of spermatocytes and the levels of the meiotic regulators and Hsp90 interactors Hsp70-2, NASP and Cdc2 are reduced. We speculate that Hsp90α may be required to maintain and to activate these regulators and/or to disassemble the synaptonemal complex that holds homologous chromosomes together. The link between fertility and Hsp90 is further supported by our finding that an Hsp90 inhibitor that can cross the blood-testis barrier can partially phenocopy the genetic defects

Geomorphic and stratigraphic evidence for an unusual tsunami or storm a few centuries ago at Anegada, British Virgin Islands

© The Author(s), 2010. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Natural Hazards 63 (2012): 51-84, doi:10.1007/s11069-010-9622-6.Waters from the Atlantic Ocean washed southward across parts of Anegada, east-northeast of Puerto Rico, during a singular event a few centuries ago. The overwash, after crossing a fringing coral reef and 1.5 km of shallow subtidal flats, cut dozens of breaches through sandy beach ridges, deposited a sheet of sand and shell capped with lime mud, and created inland fields of cobbles and boulders. Most of the breaches extend tens to hundreds of meters perpendicular to a 2-km stretch of Anegada’s windward shore. Remnants of the breached ridges stand 3 m above modern sea level, and ridges seaward of the breaches rise 2.2–3.0 m high. The overwash probably exceeded those heights when cutting the breaches by overtopping and incision of the beach ridges. Much of the sand-and-shell sheet contains pink bioclastic sand that resembles, in grain size and composition, the sand of the breached ridges. This sand extends as much as 1.5 km to the south of the breached ridges. It tapers southward from a maximum thickness of 40 cm, decreases in estimated mean grain size from medium sand to very fine sand, and contains mud laminae in the south. The sand-and-shell sheet also contains mollusks—cerithid gastropods and the bivalve Anomalocardia—and angular limestone granules and pebbles. The mollusk shells and the lime-mud cap were probably derived from a marine pond that occupied much of Anegada’s interior at the time of overwash. The boulders and cobbles, nearly all composed of limestone, form fields that extend many tens of meters generally southward from limestone outcrops as much as 0.8 km from the nearest shore. Soon after the inferred overwash, the marine pond was replaced by hypersaline ponds that produce microbial mats and evaporite crusts. This environmental change, which has yet to be reversed, required restriction of a former inlet or inlets, the location of which was probably on the island’s south (lee) side. The inferred overwash may have caused restriction directly by washing sand into former inlets, or indirectly by reducing the tidal prism or supplying sand to post-overwash currents and waves. The overwash happened after A.D. 1650 if coeval with radiocarbon-dated leaves in the mud cap, and it probably happened before human settlement in the last decades of the 1700s. A prior overwash event is implied by an inland set of breaches. Hypothetically, the overwash in 1650–1800 resulted from the Antilles tsunami of 1690, the transatlantic Lisbon tsunami of 1755, a local tsunami not previously documented, or a storm whose effects exceeded those of Hurricane Donna, which was probably at category 3 as its eye passed 15 km to Anegada’s south in 1960.The work was supported in part by the Nuclear Regulatory Commission under its project N6480, a tsunami-hazard assessment for the eastern United States

A nocturnal atmospheric loss of CH2I2 in the remote marine boundary layer.

Ocean emissions of inorganic and organic iodine compounds drive the biogeochemical cycle of iodine and produce reactive ozone-destroying iodine radicals that influence the oxidizing capacity of the atmosphere. Di-iodomethane (CH2I2) and chloro-iodomethane (CH2ICl) are the two most important organic iodine precursors in the marine boundary layer. Ship-borne measurements made during the TORERO (Tropical Ocean tRoposphere Exchange of Reactive halogens and Oxygenated VOC) field campaign in the east tropical Pacific Ocean in January/February 2012 revealed strong diurnal cycles of CH2I2 and CH2ICl in air and of CH2I2 in seawater. Both compounds are known to undergo rapid photolysis during the day, but models assume no night-time atmospheric losses. Surprisingly, the diurnal cycle of CH2I2 was lower in amplitude than that of CH2ICl, despite its faster photolysis rate. We speculate that night-time loss of CH2I2 occurs due to reaction with NO3 radicals. Indirect results from a laboratory study under ambient atmospheric boundary layer conditions indicate a k CH2I2+NO3 of ≤4 × 10-13 cm3 molecule-1 s-1; a previous kinetic study carried out at ≤100 Torr found k CH2I2+NO3 of 4 × 10-13 cm3 molecule-1 s-1. Using the 1-dimensional atmospheric THAMO model driven by sea-air fluxes calculated from the seawater and air measurements (averaging 1.8 +/- 0.8 nmol m-2 d-1 for CH2I2 and 3.7 +/- 0.8 nmol m-2 d-1 for CH2ICl), we show that the model overestimates night-time CH2I2 by >60 % but reaches good agreement with the measurements when the CH2I2 + NO3 reaction is included at 2-4 × 10-13 cm3 molecule-1 s-1. We conclude that the reaction has a significant effect on CH2I2 and helps reconcile observed and modeled concentrations. We recommend further direct measurements of this reaction under atmospheric conditions, including of product branching ratios.LJC acknowledges NERC (NE/J00619X/1) and the National Centre for Atmospheric Science (NCAS) for funding. The laboratory work was supported by the NERC React-SCI (NE/K005448/1) and RONOCO (NE/F005466/1) grants.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s10874-015-9320-