6,500 research outputs found
Tropical and temperate differences in the trophic structure and aquatic prey use of riparian predators
The influence of aquatic resource-inputs on terrestrial communities is poorly understood, particularly in the tropics. We used stable isotope analysis of carbon and nitrogen to trace aquatic prey use and quantify the impact on trophic structure in 240 riparian arthropod communities in tropical and temperate forests. Riparian predators consumed more aquatic prey and were more trophically diverse in the tropics than temperate regions, indicating tropical riparian communities are both more reliant on and impacted by aquatic resources than temperate communities. This suggests they are more vulnerable to disruption of aquatic–terrestrial linkages. Although aquatic resource use declined strongly with distance from water, we observed no correlated change in trophic structure, suggesting trophic flexibility to changing resource availability within riparian predator communities in both tropical and temperate regions. Our findings highlight the importance of aquatic resources for riparian communities, especially in the tropics, but suggest distance from water is less important than resource diversity in maintaining terrestrial trophic structure
Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication
All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories
Generation of otic lineages from integration-free human-induced pluripotent stem cells reprogrammed by mRNAs
Damage to the sensory hair cells and the spiral ganglion neurons of the cochlea leads to deafness. Induced pluripotent stem cells (iPSCs) are a promising tool to regenerate the cells in the inner ear that have been affected by pathology or have been lost. To facilitate the clinical application of iPSCs, the reprogramming process should minimize the risk of introducing undesired genetic alterations while conferring the cells the capacity to differentiate into the desired cell type. Currently, reprogramming induced by synthetic mRNAs is considered to be one of the safest ways of inducing pluripotency, as the transgenes are transiently delivered into the cells without integrating into the genome. In this study, we explore the ability of integration-free human-induced pluripotent cell lines that were reprogrammed by mRNAs, to differentiate into otic progenitors and, subsequently, into hair cell and neuronal lineages. hiPSC lines were induced to differentiate by culturing them in the presence of fibroblast growth factors 3 and 10 (FGF3 and FGF10). Progenitors were identified by quantitative microscopy, based on the coexpression of otic markers PAX8, PAX2, FOXG1, and SOX2. Otic epithelial progenitors (OEPs) and otic neuroprogenitors (ONPs) were purified and allowed to differentiate further into hair cell-like cells and neurons. Lineages were characterised by immunocytochemistry and electrophysiology. Neuronal cells showed inward Na+ () currents and outward () and inward K+ () currents while hair cell-like cells had inward and outward delayed rectifier K+ currents, characteristic of developing hair cells. We conclude that human-induced pluripotent cell lines that have been reprogrammed using nonintegrating mRNAs are capable to differentiate into otic cell types
Adiabatic sound velocity and compressibility of a trapped d-dimensional ideal anyon gas
The adiabatic sound velocity and compressibility for harmonically trapped
ideal anyons in arbitrary dimensions are calculated within Haldane fractional
exclusion statistics. The corresponding low-temperature and high-temperature
behaviors are studied in detail. To compare with the experimental result of
unitary fermions, the sound velocity for anyons in the cigar-shaped trap is
derived. The sound velocity for anyons in the disk-shaped trap is also
calculated. With the parameter g=0.287, the sound velocity of unitary fermions
in the cigar-shaped trap modeled by anyons is in good agreement with the
experimental result, while that of unitary fermions in the disk-shaped trap is
v_{0}/v_{F}=0.406 with Fermi velocity v_{F}.Comment: 16 pages, 6 figure, elsarticle.cls, minor changes with typos
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Kinetic analysis of the accumulation of a half-sandwich organo-osmium pro-drug in cancer cells
Transition of pulsed operation from Q-switching to continuous-wave mode-locking in a Yb:KLuW waveguide laser
We report on the diverse pulsed operation regimes of a femtosecond-laser-written Yb:KLuW channel waveguide laser emitting near 1040 nm. By the precise position tuning of a carbon-nanotube-coated saturable absorber (SA) mirror, the transition of the pulsed operation from Q-switching, Q-switched mode-locking and finally sub-GHz continuous-wave mode-locking are obtained based on the interplay of dispersion and mode area control. The Q-switched pulses exhibit typical fast SA Q-switched pulse characteristics depending on absorbed pump powers. In the Q-switched mode-locking, amplitude modulations of the mode-locked pulses on the Q-switched envelope are observed. The radio-frequency spectrum represents the coexistence of Q-switching and mode-locking signals. In the purely mode-locked operation, the waveguide laser generates 2.05-ps pulses at 0.5 GHz.National Research Foundation of Korea (2018H1A2AA1061480, 2019R1A2C3003504, 2020R1A4A2002828); Spanish Government (FIS2017-87970-R, MAT2016-75716-C2-1-R (AEI/FEDER,UE)); Junta de Castilla y León (SA287P18); Generalitat de Catalunya (2017SGR755)
Half-sandwich arene ruthenium(II) and osmium(II) thiosemicarbazone complexes : solution behavior and antiproliferative activity
We report the synthesis, characterization and antiproliferative activity of organo-osmium(II) and organo-ruthenium(II) half-sandwich complexes [(η6-p-cym)Os(L)Cl]Cl (1 and 2) and [(η6-p-cym)Ru(L)Cl]Cl (3 and 4), where L = N-(2-hydroxy)-3-metoxybenzylidenethiosemicarbazide (L1) or N-(2,3-dihydroxybenzylidene)-3-phenylthiosemicarbazide (L2), respectively. X-ray crystallography showed that all four complexes possess half-sandwich pseudo-octahedral “three- leg piano-stool” structures, with a neutral N,S-chelating thiosemicarbazone ligand and a terminal chloride occupying three coordinative positions. In methanol, E/Z isomerization of the coordinated thiosemicarbazone ligand was observed, while in an aprotic solvent like acetone, partial dissociation of the ligand occurs, reaching complete displacement in a more coordinating solvent like DMSO. In general, the complexes exhibited good activity towards A2780 ovarian, A2780Cis cisplatin-resistant ovarian, A549 lung, HCT116 colon, and PC3 prostate cancer cells. In particular ruthenium complex 3 does not present cross-resistance with the clinical drug cisplatin in the A2780 human ovarian cancer cell line. The complexes were more active than the free thiosemicarbazone ligands, especially in A549 and HCT116 cells with po- tency improvements of up to 20-fold between the organic ligand L1 and the ruthenium complex 1
Photoactivatable cell-selective dinuclear trans diazido platinum(IV) anticancer prodrugs
Novel all-trans dinuclear PtIV complexes bridged by a dicarboxylate linker, highly stable in the dark, generate azidyl and hydroxyl radicals upon irradiation with blue light. They are photocytotoxic to human cancer cells, whereas cisplatin was inactive under these conditions and more photoactive toward cisplatin-resistant ovarian cancer cells compared to wild-type cells. Remarkably, the dinuclear complexes were relatively nontoxic toward normal human cells. Cell cycle and DNA binding experiments suggested that DNA is a target
Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative
[Abstract] Objective To find autoantibodies (AAbs) in serum that could be useful to predict incidence of radiographic knee osteoarthritis (KOA).
Design A Nucleic-acid Programmable Protein Arrays (NAPPA) platform was used to screen AAbs against 2125 human proteins in sera at baseline from participants free of radiographic KOA belonging to the incidence and non-exposed subcohorts of the Osteoarthritis Initiative (OAI) who developed or not, radiographic KOA during a follow-up period of 96 months. NAPPA-ELISA were performed to analyse reactivity against methionine adenosyltransferase two beta (MAT2β) and verify the results in 327 participants from the same subcohorts. The association of MAT2β-AAb levels with KOA incidence was assessed by combining several robust biostatistics analysis (logistic regression, Receiver Operating Characteristic and Kaplan-Meier curves). The proposed prognostic model was replicated in samples from the progression subcohort of the OAI.
Results In the screening phase, six AAbs were found significantly different at baseline in samples from incident compared with non-incident participants. In the verification phase, high levels of MAT2β-AAb were significantly associated with the future incidence of KOA and with an earlier development of the disease. The incorporation of this AAb in a clinical model for the prognosis of incident radiographic KOA significantly improved the identification/classification of patients who will develop the disorder. The usefulness of the model to predict radiographic KOA was confirmed on a different OAI subcohort.
Conclusions The measurement of AAbs against MAT2β in serum might be highly useful to improve the prediction of OA development, and also to estimate the time to incidence.Instituto de Salud Carlos III; PT17/0019/0014Instituto de Salud Carlos III; PI14/01707Instituto de Salud Carlos III; PI16/02124Instituto de Salud Carlos III; PI17/00404Instituto de Salud Carlos III; DTS17/00200Instituto de Salud Carlos III; CIBER-BBN CB06/01/0040Insituto de Salud Carlos III; CIBER-ONC CB16/12/00400Instituto de Salud Carlos III; RETIC-RIER-RD12/0009/0018Xunta de Galicia; IN606A-2016/012Instituto de Salud Carlos III; CPII17/0026Insituto de Salud Carlos III; CPII15/0001
Transfer hydrogenation and antiproliferative activity of tethered half-sandwich organoruthenium catalysts
We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η6-Ph(CH2)3-ethylenediamine-N-R)Cl], where R = methanesulfonyl (Ms, 1), toluenesulfonyl (Ts, 2), 4-trifluoromethylbenzenesulfonyl (Tf, 3), and 4-nitrobenzenesulfonyl (Nb, 4), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, and breast cancer cell lines. Complex 2 in particular exhibits a low cross-resistance with cisplatin. The complexes show potent catalytic activity in the transfer hydrogenation of NAD+ to NADH with formate as hydride donor in aqueous solution (310 K, pH 7). Substituents on the chelated ligand decreased the turnover frequency in the order Nb > Tf > Ts > Ms. An enhancement of antiproliferative activity (up to 22%) was observed on coadministration with nontoxic concentrations of sodium formate (0.5–2 mM). Complex 2 binds to nucleobase guanine (9-EtG), but DNA appears not to be the target, as little binding to calf thymus DNA or bacterial plasmid DNA was observed. In addition, complex 2 reacts rapidly with glutathione (GSH), which might hamper transfer hydrogenation reactions in cells. Complex 2 induced a dose-dependent G1 cell cycle arrest after 24 h exposure in A2780 human ovarian cancer cells while promoting an increase in reactive oxygen species (ROS), which is likely to contribute to its antiproliferative activity
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