| 1. |
- Kasliwal, M. M., et al.
(author)
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Illuminating gravitational waves : A concordant picture of photons from a neutron star merger
- 2017
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6370, s. 1559-
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Journal article (peer-reviewed)abstract
- Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.
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| 2. |
- Jencson, Jacob E., et al.
(author)
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The SPIRITS Sample of Luminous Infrared Transients : Uncovering Hidden Supernovae and Dusty Stellar Outbursts in Nearby Galaxies
- 2019
-
In: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 886:1
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Journal article (peer-reviewed)abstract
- We present a systematic study of the most luminous (M-IR [Vega magnitudes] brighter than ?14) infrared (IR) transients discovered by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) between 2014 and 2018 in nearby galaxies (D < 35 Mpc). The sample consists of nine events that span peak IR luminosities of M-[4.5],M-peak between ?14 and ?18.2, show IR colors between 0.2;<;([3.6]?[4.5]);<;3.0, and fade on timescales between 55 days;t(fade);<;480 days. The two reddest events (A(V) > 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type;Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2;A(V);<;8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as
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| 3. |
- Barnes, Ashley T., et al.
(author)
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Young massive star cluster formation in the Galactic Centre is driven by global gravitational collapse of high-mass molecular clouds
- 2019
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 486:1, s. 283-303
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Journal article (peer-reviewed)abstract
- Young massive clusters (YMCs) are the most compact, high-mass stellar systems still forming at the present day. The precursor clouds to such systems are, however, rare due to their large initial gas mass reservoirs and rapid dispersal time-scales due to stellar feedback. None the less, unlike their high-z counterparts, these precursors are resolvable down to the sites of individually forming stars, and hence represent the ideal environments in which to test the current theories of star and cluster formation. Using high angular resolution (1 arcsec / 0.05 pc) and sensitivity ALMA observations of two YMC progenitor clouds in the Galactic Centre, we have identified a suite of molecular line transitions - e.g. c-C3H2 (7 - 6) - that are believed to be optically thin, and reliably trace the gas structure in the highest density gas on star-forming core scales. We conduct a virial analysis of the identified core and proto-cluster regions, and show that half of the cores (5/10) and both proto-clusters are unstable to gravitational collapse. This is the first kinematic evidence of global gravitational collapse in YMC precursor clouds at such an early evolutionary stage. The implications are that if these clouds are to form YMCs, then they likely do so via the 'conveyor-belt' mode, whereby stars continually form within dispersed dense gas cores as the cloud undergoes global gravitational collapse. The concurrent contraction of both the cluster-scale gas and embedded (proto-)stars ultimately leads to the high (proto-)stellar density in YMCs.
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| 4. |
- Jencson, Jacob E., et al.
(author)
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Discovery of an Intermediate-luminosity Red Transient in M51 and Its Likely Dust-obscured, Infrared-variable Progenitor
- 2019
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 880:2
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Journal article (peer-reviewed)abstract
- We present the discovery of an optical transient (OT) in Messier. 51, designated M51 OT2019-1 (also ZTF 19aadyppr, AT 2019abn, ATLAS19bz1), by the Zwicky Transient Facility (ZTF). The OT rose over 15. days to an observed luminosity of M-r = -13 (nu L-nu = 9 x 10(6) L-circle dot), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of approximate to 400 km s(-1), Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called SN impostors and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a 4.5 mu m luminosity of M-[4.5] approximate to -12.2 mag and a [3.6]-[4.5] color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [ 4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of E(B - V) approximate to 0.7 mag and higher intrinsic luminosity of M-r approximate to -14.9 mag (nu L-nu = 5.3 x 10(7) L-circle dot) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51. OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.
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| 5. |
- Elia, Davide, et al.
(author)
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The Hi-GAL compact source catalogue - II. The 360° catalogue of clump physical properties
- 2021
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 504:2, s. 2742-2766
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Journal article (peer-reviewed)abstract
- We present the 360° catalogue of physical properties of Hi-GAL compact sources, detected between 70 and 500 $\mu$m. This release not only completes the analogous catalogue previously produced by the Hi-GAL collaboration for -71° 2 á 2 67°, but also meaningfully improves it because of a new set of heliocentric distances, 120 808 in total. About a third of the 150 223 entries are located in the newly added portion of the Galactic plane. A first classification based on detection at 70 $\mu$m as a signature of ongoing star-forming activity distinguishes between protostellar sources (23 per cent of the total) and starless sources, with the latter further classified as gravitationally bound (pre-stellar) or unbound. The integral of the spectral energy distribution, including ancillary photometry from λ = 21 to 1100 $\mu$m, gives the source luminosity and other bolometric quantities, while a modified blackbody fitted to data for $\lambda \ge 160∼\mu$m yields mass and temperature. All tabulated clump properties are then derived using photometry and heliocentric distance, where possible. Statistics of these quantities are discussed with respect to both source Galactic location and evolutionary stage. No strong differences in the distributions of evolutionary indicators are found between the inner and outer Galaxy. However, masses and densities in the inner Galaxy are on average significantly larger, resulting in a higher number of clumps that are candidates to host massive star formation. Median behaviour of distance-independent parameters tracing source evolutionary status is examined as a function of the Galactocentric radius, showing no clear evidence of correlation with spiral arm positions.
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| 6. |
- Ginsburg, A., et al.
(author)
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Dense gas in the Galactic central molecular zone is warm and heated by turbulence
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586, s. Art nr A50-
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Journal article (peer-reviewed)abstract
- Context. The Galactic center is the closest region where we can study star formation under extreme physical conditions like those in high-redshift galaxies. Aims. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. Methods. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H2CO) transitions. We used the 3(2,1)-2(2,0)/3(0,3)-2(0,2) line ratio to determine the gas temperature in n similar to 10(4) - 10(5) cm(-3) gas. We have produced temperature maps and cubes with 30 0 0 and 1 km s(-1) resolution and published all data in FITS form. Results. Dense gas temperatures in the Galactic center range from similar to 60 K to > 100 K in selected regions. The highest gas temperatures T-G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km s(-1) and 50 km s(-1) clouds, and in "The Brick" (G0.253 + 0.016). We infer an upper limit on the cosmic ray ionization rate zeta(CR)
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| 7. |
- Sattui, Sebastian E., et al.
(author)
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Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study
- 2021
-
In: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864
-
Journal article (peer-reviewed)abstract
- Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
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| 8. |
- Stanke, T., et al.
(author)
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The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
-
Journal article (peer-reviewed)abstract
- Context. The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims. Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(32) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods. We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(32) transition, obtained using SuperCAM on APEX at an angular resolution of 19 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results. We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few sub-regions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H II region, where we argue that the bulk of the molecular gas is in the foreground of the H II region. High CO(32)/CO(10) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023 & NGC 2024 region facing the IC 434 H II region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term Cow Nebula globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the extremely high velocity regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow.
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| 9. |
- Svoboda, B. E., et al.
(author)
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THE BOLOCAM GALACTIC PLANE SURVEY. XIV. PHYSICAL PROPERTIES of MASSIVE STARLESS and STAR-FORMING CLUMPS
- 2016
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 822:2
-
Journal article (peer-reviewed)abstract
- We sort 4683 molecular clouds between 10° < ℓ < 65° from the Bolocam Galactic Plane Survey based on observational diagnostics of star formation activity: compact 70 μm sources, mid-IR color-selected YSOs, H2O and CH3OH masers, and UCH ii regions. We also present a combined NH3-derived gas kinetic temperature and H2O maser catalog for 1788 clumps from our own GBT 100 m observations and from the literature. We identify a subsample of 2223 (47.5%) starless clump candidates (SCCs), the largest and most robust sample identified from a blind survey to date. Distributions of flux density, flux concentration, solid angle, kinetic temperature, column density, radius, and mass show strong (>1 dex) progressions when sorted by star formation indicator. The median SCC is marginally subvirial (α ∼ 0.7) with >75% of clumps with known distance being gravitationally bound (α < 2). These samples show a statistically significant increase in the median clump mass of ΔM ∼ 170-370 M o from the starless candidates to clumps associated with protostars. This trend could be due to (i) mass growth of the clumps at M o Myr-1 for an average freefall 0.8 Myr timescale, (ii) a systematic factor of two increase in dust opacity from starless to protostellar phases, and/or (iii) a variation in the ratio of starless to protostellar clump lifetime that scales as ∼M -0.4. By comparing to the observed number of CH3OH maser containing clumps, we estimate the phase lifetime of massive (M > 103 M o) starless clumps to be 0.37 ± 0.08 Myr (M/103 M o)-1; the majority (M < 450 M o) have phase lifetimes longer than their average freefall time. © 2016. The American Astronomical Society. All rights reserved.
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| 10. |
- Aurelle, D., et al.
(author)
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Biodiversity, climate change, and adaptation in the Mediterranean
- 2022
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In: Ecosphere. - : Wiley. - 2150-8925. ; 13:4
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Journal article (peer-reviewed)abstract
- Potential for, and limits to, adaptation to environmental changes are critical for resilience and risk mitigation. The Mediterranean basin is a mosaic of biodiversity-rich ecosystems long affected by human influence, whose resilience is now questioned by climate change. After reviewing the different components of biological adaptation, we present the main characteristics of marine and terrestrial biodiversity in the Mediterranean basin and of the pressures they face. Taking climatic trends into consideration, we discuss the adaptive potential of a range of ecosystems dominated by species without active dispersal. We argue that the high heterogeneity of Mediterranean landscapes and seascapes constitutes a laboratory for the study of adaptation when environmental conditions change rapidly and may provide opportunities for adaptation and adaptability of species and ecosystems. Adaptive management in the Mediterranean can and should harness the nature-based solutions offered by both ecological and evolutionary processes for increasing the resilience of ecosystems to climate change.
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| 11. |
- Rimkute, Inga, et al.
(author)
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Histo-blood group antigens of glycosphingolipids predict susceptibility of human intestinal enteroids to norovirus infection
- 2020
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In: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 295:47, s. 15974-15987
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Journal article (peer-reviewed)abstract
- The molecular mechanisms behind infection and propagation of human restricted pathogens such as human norovirus (HuNoV) have defied interrogation because they were previously unculturable. However, human intestinal enteroids (HIEs) have emerged to offer unique ex vivo models for targeted studies of intestinal biology, including inflammatory and infectious diseases. Carbohydrate-dependent histo-blood group antigens (HBGAs) are known to be critical for clinical infection. To explore whether HBGAs of glycosphingolipids contribute to HuNoV infection, we obtained HIE cultures established from stem cells isolated from jejunal biopsies of six individuals with different ABO, Lewis, and secretor genotypes. We analyzed their glycerolipid and sphingolipid compositions and quantified interaction kinetics and the affinity of HuNoV virus-like particles (VLPs) to lipid vesicles produced from the individual HIE-lipid extracts. All HIEs had a similar lipid and glycerolipid composition. Sphingolipids included HBGA-related type 1 chain glycosphingolipids (GSLs), with HBGA epitopes corresponding to the geno- and phenotypes of the different HIEs. As revealed by single-particle interaction studies of Sydney GII.4 VLPs with glycosphingolipid-containing HIE membranes, both binding kinetics and affinities explain the patterns of susceptibility toward GII.4 infection for individual HIEs. This is the first time norovirus VLPs have been shown to interact specifically with secretor gene-dependent GSLs embedded in lipid membranes of HIEs that propagate GII.4 HuNoV ex vivo, highlighting the potential of HIEs for advanced future studies of intestinal glycobiology and host-pathogen interactions.
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| 12. |
- Bally, Marta, 1981, et al.
(author)
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Fluorescent vesicles for signal amplification in reverse phase protein microarray assays
- 2011
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In: Analytical Biochemistry. - 0003-2697 .- 1096-0309. ; 416:2, s. 145-151
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Journal article (peer-reviewed)abstract
- Developments in microarray technology promise to lead to great advancements in the biomedical and biological field. However, implementation of these analytical tools often relies on signal amplification strategies that are essential to reach the sensitivity levels required for a variety of biological applications. This is true especially for reverse phase arrays where a complex biological sample is directly immobilized on the chip. We present a simple and generic method for signal amplification based on the use of antibody-tagged fluorescent vesicles as labels for signal generation. To assess the gain in assay sensitivity, we performed a model assay for the detection of rabbit immunoglobulin G (IgG) and compared the limit of detection (LOD) of the vesicle assay with the LOD of a conventional assay performed with fluorescent reporter molecules. We evaluated the improvements for two fluorescence-based transduction setups: a high-sensitivity microarray reader (ZeptoREADER) and a conventional confocal scanner. In all cases, our strategy led to an increase in sensitivity. However, gain in sensitivity widely depended on the type of illumination; whereas an approximately 2-fold increase in sensitivity was observed for readout based on evanescent field illumination, the contribution was as high as more than 200-fold for confocal scanning. (C) 2011 Elsevier Inc. All rights reserved.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Nasir, Waqas, et al.
(author)
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Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes
- 2017
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In: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 12:5, s. 1288-1296
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Journal article (peer-reviewed)abstract
- Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane associated glycans is more restricted than that of glycans in solution, particularly because of orientational constraints imposed on the glycolipid through its lateral interactions with other membrane lipids and proteins. We have developed and employed a total internal reflection fluorescence microscopy-based binding assay and. a scheme for molecular dynamics (MD) membrane simulations to investigate the consequences of various glycan presentation effects. The system studied was histo-blood group antigen (HBGA) epitopes of membrane-bound glycosphingolipids (GSLs) derived from small intestinal epithelium of humans (type 1 chain) and dogs (type 2 chain) interacting with GII.4 norovirus-like particles. Our experimental results showed strong binding to all lipid-linked type 1 chain HBGAs but no or only weak binding to the corresponding type 2 chain HBGAs. This is in contrast to results derived from STD experiments with free HBGAs in solution where binding was observed for Lewis x. The MD data suggest that the strong binding to type 1 chain glycolipids was due to the well-exposed (1,2)-linked alpha-L-Fucp and (1,4)- linked alpha-L-Fucp residues, while the weaker binding or lack of binding to type 2 chain HBGAs was due to the very restricted accessibility of the (1,3) -linked alpha-L-Fucp residue when the glycolipid is embedded in a phospholipid membrane. Our results not only contribute to a general understanding of protein carbohydrate interactions on model membrane surfaces, particularly in the context of virus binding, but also suggest a possible role of human intestinal GSLs as potential receptors for norovirus uptake.
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| 17. |
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| 18. |
- Peerboom, Nadia, 1990, et al.
(author)
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Binding Kinetics and Lateral Mobility of HSV-1 on End-Grafted Sulfated Glycosaminoglycans
- 2017
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 113:6, s. 1223-1234
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Journal article (peer-reviewed)abstract
- Many viruses, including herpes simplex (HSV), are recruited to their host cells via interaction between their envelope glycoproteins and cell-surface glycosaminoglycans (GAGs). This initial attachment is of a multivalent nature, i.e., it requires the establishment of multiple bonds between amino acids of viral glycoproteins and sulfated saccharides on the GAG chain. To gain understanding of how this binding process is modulated, we performed binding kinetics and mobility studies using end-grafted GAG chains that mimic the end attachment of these chains to proteoglycans. Total internal reflection fluorescence microscopy was used to probe binding and release, as well as the diffusion of single HSV-1 particles. To verify the hypothesis that the degree of sulfation, but also the arrangement of sulfate groups along the GAG chain, plays a key role in HSV binding, we tested two native GAGs (chondroitin sulfate and heparan sulfate) and compared our results to chemically sulfated hyaluronan. HSV-1 recognized all sulfated GAGs, but not the nonsulfated hyaluronan, indicating that binding is specific to the presence of sulfate groups. Furthermore we observed that a notable fraction of GAG-bound virions exhibit lateral mobility, although the multivalent binding to the immobilized GAG brushes ensures firm virus attachment to the interface. Diffusion was faster on the two native GAGs, one of which, chondroitin sulfate, was also characterized by the highest association rate per GAG chain. This highlights the complexity of multivalent virus-GAG interactions and suggests that the spatial arrangement of sulfates along native GAG chains may play a role in modulating the characteristics of the HSV-GAG interaction. Altogether, these results, obtained with a minimal and well-controlled model of the cell membrane, provide, to our knowledge, new insights into the dynamics of the HSV-GAG interaction.
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| 19. |
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| 20. |
- Thomas, Anitha M., et al.
(author)
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Development of a liposomal nanoparticle formulation of 5-Fluorouracil for parenteral administration : Formulation design, pharmacokinetics and efficacy
- 2011
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In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 150:2, s. 212-219
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Journal article (peer-reviewed)abstract
- 5-Fluorouracil (5-FU) is a small, very membrane permeable drug that is poorly retained within the aqueous compartment of liposomal nanoparticles (LNP). To address this problem a novel method relying on formation of a ternary complex comprising copper, low molecular weight polyethylenimine (PEI) and 5-FU has been developed. More specifically, in the presence of entrapped copper and PEI, externally added 5-FU can be efficiently encapsulated (>95%) in DSPC/Chol (1,2-Distearoyl-sn-Glycero-3-Phosphocholine/cholesterol; 55:45mol%) liposomes (130-170nm) to achieve drug-to-lipid ratios of 0.1 (mol:mol). Drug release studies completed using this LNP formulation of 5-FU demonstrated significant improvements in drug retention in vitro and in vivo. Plasma concentrations of 5-FU were 7- to 23-fold higher when the drug was administered intravenously to mice as the LNP 5-FU formulation compared to free 5-FU. Further, the therapeutic effects of the LNP 5-FU formulation, as determined in a HT-29 subcutaneous colorectal cancer model where treatment was given QDx5, was greater than that which could be achieved with free 5-FU when compared at equivalent doses. This is the first time an active loading method has been described for 5-FU. The use of ternary metal complexation strategy to encapsulate therapeutic agents may define a unique platform for preparation of LNP drug formulations.
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| 21. |
- Wasan, E K, et al.
(author)
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A multi-step lipid mixing assay to model structural changes in cationic lipoplexes used for in vitro transfection
- 1999
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In: Biochimica et Biophysica Acta - Biomembranes. - 0005-2736 .- 1879-2642. ; 1461:1, s. 27-46
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Journal article (peer-reviewed)abstract
- Formation of liposome/polynucleotide complexes (lipoplexes) involves electrostatic interactions, which induce changes in liposome structure. The ability of these complexes to transfer DNA into cells is dependent on the physicochemical attributes of the complexes, therefore characterization of binding-induced changes in liposomes is critical for the development of lipid-based DNA delivery systems. To clarify the apparent lack of correlation between membrane fusion and in vitro transfection previously observed, we performed a multi-step lipid mixing assay to model the sequential steps involved in transfection. The roles of anion charge density, charge ratio and presence of salt on lipid mixing and liposome aggregation were investigated. The resonance-energy transfer method was used to monitor lipid mixing as cationic liposomes (DODAC/DOPE and DODAC/DOPC; 1:1 mole ratio) were combined with plasmid, oligonucleotides or Na(2)HPO(4). Cryo-transmission electron microscopy was performed to assess morphology. As plasmid or oligonucleotide concentration increased, lipid mixing and aggregation increased, but with Na(2)HPO(4) only aggregation occurred. NaCl (150 mM) reduced the extent of lipid mixing. Transfection studies suggest that the presence of salt during complexation had minimal effects on in vitro transfection. These data give new information about the effects of polynucleotide binding to cationic liposomes, illustrating the complicated nature of anion induced changes in liposome morphology and membrane behavior.
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