bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases
Authors: Evangelisti Elisa , Cascella Roberta , Becatti Matteo , Marrazza Giovanna , Dobson Christopher M. , Chiti Fabrizio , Stefani Massimo , Cecchi Cristina 
Published: September 2016

AbstractThe conversion of peptides or proteins from their soluble native states into intractable amyloid deposits is associated with a wide range of human disorders. Misfolded protein oligomers formed during the process of aggregation have been identified as the primary pathogenic agents in many such conditions. Here, we show the existence of a quantitative relationship between the degree of binding to neuronal cells of different types of oligomers formed from a model protein, HypF-N, and the GM1 content of the plasma membranes. In addition, remarkably similar behavior is observed for oligomers of the Aβ42 peptide associated with Alzheimer’s disease. Further analysis has revealed the existence of a linear correlation between the level of the influx of Ca2+ across neuronal membranes that triggers cellular damage, and the fraction of oligomeric species bound to the membrane. Our findings indicate that the susceptibility of neuronal cells to different types of misfolded oligomeric assemblies is directly related to the extent of binding of such oligomers to the cellular membrane.
Microwave ablation of hepatocellular carcinoma as first-line treatment: long term outcomes and prognostic factors in 221 patients
Authors: Wang Tao , Lu Xiao-Jie , Chi Jia-Chang , Ding Min , Zhang Yuan , Tang Xiao-Yin , Li Ping , Zhang Li , Zhang Xiao-Yu , Zhai Bo 
Published: September 2016

AbstractThis retrospective study aimed at evaluating the long-term outcomes and prognostic factors of microwave ablation (MWA) as a first-line treatment for hepatocellular carcinoma (HCC). 221 consecutive patients receiving MWA in our center between October 11, 2010 and December 31, 2013 were enrolled. Technique effectiveness was evaluated one month post-ablation. Initial complete ablation (CA1st) was gained in 201 (90.95%) patients, secondary CA (CA2nd) in 8 (3.62%) patients and the remaining 12 (5.43%) patients suffered from incomplete ablation (IA2nd) after two sessions of MWA. Patients with tumor size >5 cm were less likely to gain CA1st. Procedure-related complications were recorded and no procedure-related death occurred. 22 (10.4%) complications occurred with 8 (3.8%) being major ones. Tumor characteristics (size, number, location) do not significantly influence complication rates. After a median follow-up of 41.0 (ranging 25.0–63.5) months, the median RFS and OS was 14.0 months (95% CI: 9.254–18.746) and 41.0 months (95% CI: 33.741–48.259) respectively. Multivariate analysis identified two significant prognosticators (levels of alpha fetal protein [AFP] and gamma-glutamyl transpeptidase [GGT]) of RFS and five significant prognosticators (tumor number, tumor size, AFP, GGT and recurrence type) of OS. In conclusion, MWA provides high technique effectiveness rate and is well tolerated in patients with HCC as a first-line treatment.
The multifaceted RisA regulon of Bordetella pertussis
Authors: Coutte Loïc , Huot Ludovic , Antoine Rudy , Slupek Stephanie , Merkel Tod J. , Chen Qing , Stibitz Scott , Hot David , Locht Camille 
Published: September 2016

AbstractThe whooping cough agentBordetella pertussisregulates the production of its virulence factors by the BvgA/S system. Phosphorylated BvgA activates the virulence-activated genes (vags) and represses the expression of the virulence-repressed genes (vrgs) via the activation of thebvgRgene. In modulating conditions, with MgSO4, the BvgA/S system is inactive, and thevrgs are expressed. Here, we show that the expression of almost allvrgs depends on RisA, another transcriptional regulator. We also show that somevags are surprisingly no longer modulated by MgSO4in therisA−background. RisA also regulates the expression of other genes, including chemotaxis and flagellar operons, iron-regulated genes, and genes of unknown function, which may or may not be controlled by BvgA/S. We identified RisK as the likely cognate RisA kinase and found that it is important for expression of most, but not all RisA-regulated genes. This was confirmed using the phosphoablative RisAD60N and the phosphomimetic RisAD60E analogues. Thus the RisA regulon adds a new layer of complexity toB. pertussisvirulence gene regulation.
Molecular organization, localization and orientation of antifungal antibiotic amphotericin B in a single lipid bilayer
Authors: Grudzinski Wojciech , Sagan Joanna , Welc Renata , Luchowski Rafal , Gruszecki Wieslaw I. 
Published: September 2016

AbstractAmphotericin B is a popular antifungal antibiotic, a gold standard in treatment of systemic mycotic infections, due to its high effectiveness. On the other hand, applicability of the drug is limited by its considerable toxicity to patients. Biomembranes are a primary target of physiological activity of amphotericin B and both the pharmacologically desired and toxic side effects of the drug relay on its molecular organization in the lipid phase. In the present work, molecular organization, localization and orientation of amphotericin B, in a single lipid bilayer system, was analysed simultaneously, thanks to application of a confocal fluorescence lifetime imaging microscopy of giant unilamellar vesicles. The results show that the presence of sterols, in the lipid phase, promotes formation of supramolecular structures of amphotericin B and their penetration into the membrane hydrophobic core. The fact that such an effect is substantially less pronounced in the case ofcholesterol than ergosterol, the sterol of fungal membranes, provides molecular insight into the selectivity of the drug.
The yeast Aft2 transcription factor determines selenite toxicity by controlling the low affinity phosphate transport system
Authors: Pérez-Sampietro María , Serra-Cardona Albert , Canadell David , Casas Celia , Ariño Joaquín , Herrero Enrique 
Published: September 2016

AbstractThe yeast Saccharomyces cerevisiae is employed as a model to study the cellular mechanisms of toxicity and defense against selenite, the most frequent environmental selenium form. We show that yeast cells lacking Aft2, a transcription factor that together with Aft1 regulates iron homeostasis, are highly sensitive to selenite but, in contrast to aft1 mutants, this is not rescued by iron supplementation. The absence of Aft2 strongly potentiates the transcriptional responses to selenite, particularly for DNA damage- and oxidative stress-responsive genes, and results in intracellular hyperaccumulation of selenium. Overexpression of PHO4, the transcriptional activator of the PHO regulon under low phosphate conditions, partially reverses sensitivity and hyperaccumulation of selenite in a way that requires the presence of Spl2, a Pho4-controlled protein responsible for post-transcriptional downregulation of the low-affinity phosphate transporters Pho87 and Pho90. SPL2 expression is strongly downregulated in aft2 cells, especially upon selenite treatment. Selenite hypersensitivity of aft2 cells is fully rescued by deletion of PHO90, suggesting a major role for Pho90 in selenite uptake. We propose that the absence of Aft2 leads to enhanced Pho90 function, involving both Spl2-dependent and independent events and resulting in selenite hyperaccumulation and toxicity.
Cold tolerance is unaffected by oxygen availability despite changes in anaerobic metabolism
Authors: Boardman Leigh , Sørensen Jesper G. , Koštál Vladimír , Šimek Petr , Terblanche John S. 
Published: September 2016

AbstractInsect cold tolerance depends on their ability to withstand or repair perturbations in cellular homeostasis caused by low temperature stress. Decreased oxygen availability (hypoxia) can interact with low temperature tolerance, often improving insect survival. One mechanism proposed for such responses is that whole-animal cold tolerance is set by a transition to anaerobic metabolism. Here, we provide a test of this hypothesis in an insect model system (Thaumatotibia leucotreta) by experimental manipulation of oxygen availability while measuring metabolic rate, critical thermal minimum (CTmin), supercooling point and changes in 43 metabolites in moth larvae at three key timepoints (before, during and after chill coma). Furthermore, we determined the critical oxygen partial pressure below which metabolic rate was suppressed (c. 4.5 kPa). Results showed that altering oxygen availability did not affect (non-lethal) CTminnor (lethal) supercooling point. Metabolomic profiling revealed the upregulation of anaerobic metabolites and alterations in concentrations of citric acid cycle intermediates during and after chill coma exposure. Hypoxia exacerbated the anaerobic metabolite responses induced by low temperatures. These results suggest that cold tolerance ofT. leucotretalarvae is not set by oxygen limitation, and that anaerobic metabolism in these larvae may contribute to their ability to survive in necrotic fruit.
Aspect-ratio driven evolution of high-order resonant modes and near-field distributions
in localized surface phonon polariton nanostructures
Authors: Ellis Chase T. , Tischler Joseph G. , Glembocki Orest J. , Bezares Francisco J. , Giles Alexander J. , Kasica Richard , Shirey Loretta , Owrutsky Jeffrey C. , Chigrin Dmitry N. , Caldwell Joshua D. 
Published: September 2016

AbstractPolar dielectrics have garnered much attention as an alternative to plasmonic metals
in the mid- to long-wave infrared spectral regime due to their low optical losses.
As such, nanoscale resonators composed of these materials demonstrate figures of
merit beyond those achievable in plasmonic equivalents. However, until now, only
low-order, phonon-mediated, localized polariton resonances, known as surface phonon
polaritons (SPhPs), have been observed in polar dielectric optical resonators. In
the present work, we investigate the excitation of 16 distinct high-order,
multipolar, localized surface phonon polariton resonances that are optically excited
in rectangular pillars etched into a semi-insulating silicon carbide substrate. By
elongating a single pillar axis we are able to significantly modify the far- and
near-field properties of localized SPhP resonances, opening the door to realizing
narrow-band infrared sources with tailored radiation patterns. Such control of the
near-field behavior of resonances can also impact surface enhanced infrared optical
sensing, which is mediated by polarization selection rules, as well as the
morphology and strength of resonator hot spots. Furthermore, through the careful
choice of polar dielectric material, these results can also serve as the guiding
principles for the generalized design of optical devices that operate from the mid-
to far-infrared.
PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma
Authors: Kanteti Rajani , Riehm Jacob J. , Dhanasingh Immanuel , Lennon Frances E. , Mirzapoiazova Tamara , Mambetsariev Bolot , Kindler Hedy L. , Salgia Ravi 
Published: September 2016

AbstractMalignant pleural mesothelioma (MPM) is an aggressive cancer that is commonly associated with prior asbestos exposure. Receptor tyrosine kinases (RTKs) such as MET and its downstream target PI3K are overexpressed and activated in a majority of MPMs. Here, we studied the combinatorial therapeutic efficacy of the MET/ALK inhibitor crizotinib, with either a pan-class I PI3K inhibitor, BKM120, or with a PI3K/mTOR dual inhibitor, GDC-0980, in mesothelioma. Cell viability results showed that MPM cells were highly sensitive to crizotinib, BKM120 and GDC-0980 when used individually and their combination was more effective in suppressing growth. Treatment of MPM cells with these inhibitors also significantly decreased cell migration, and the combination of them was synergistic. Treatment with BKM120 alone or in combination with crizotinib induced G2-M arrest and apoptosis. Both crizotinib and BKM120 strongly inhibited the activity of MET and PI3K as evidenced by the decreased phosphorylation of MET, AKT and ribosomal S6 kinase. Using a PDX mouse model, we showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent.
Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site
Authors: Lanekoff Ingela , Cha Jeeyeon , Kyle Jennifer E. , Dey Sudhansu K. , Laskin Julia , Burnum-Johnson Kristin E. 
Published: September 2016

AbstractHere we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/d), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/d mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis.
HSCCC-based strategy for preparative separation of in vivo metabolites after administration of an herbal medicine: Saussurea laniceps, a case study
Authors: Yi Tao , Zhu Lin , Zhu Guo-Yuan , Tang Yi-Na , Xu Jun , Fan Jia-Yi , Zhao Zhong-Zhen , Chen Hu-Biao 
Published: September 2016

AbstractThis paper reports a novel strategy based on high-speed counter-current chromatography (HSCCC) technique to separate in vivo metabolites from refined extract of urine after administration of an herbal medicine. Saussurea laniceps (SL) was chosen as a model herbal medicine to be used to test the feasibility of our proposed strategy. This strategy succeeded in the case of separating four in vivo metabolites of SL from the urine of rats. Briefly, after oral administration of SL extract to three rats for ten days (2.0 g/kg/d), 269.1 mg of umbelliferone glucuronide (M1, purity, 92.5%), 432.5 mg of scopoletin glucuronide (M2, purity, 93.2%), 221.4 mg of scopoletin glucuronide (M3, purity, 92.9%) and 319.0 mg of scopoletin glucuronide (M4, purity, 90.4%) were separated from 420 mL of the rat urine by HSCCC using a two-phase solvent system composed of methyl tert-butyl ether–n-butanol–acetonitrile–water (MTBE–n-BuOH–ACN–H2O) at a volume ratio of 10:30:11:49. The chemical structures of the four metabolites, M1 to M4, were confirmed by MS and 1H, 13C NMR. As far as we know, this is the first report of the successful separation of in vivo metabolites by HSCCC after administration of an herbal medicine.
Precise Characterisation of Molecular Orientation in a Single Crystal Field-Effect Transistor Using Polarised Raman Spectroscopy
Authors: Wood Sebastian , Rigas Grigorios-Panagiotis , Zoladek-Lemanczyk Alina , Blakesley James C. , Georgakopoulos Stamatis , Mas-Torrent Marta , Shkunov Maxim , Castro Fernando A. 
Published: September 2016

AbstractCharge transport in organic semiconductors is strongly dependent on the molecular orientation and packing, such that manipulation of this molecular packing is a proven technique for enhancing the charge mobility in organic transistors. However, quantitative measurements of molecular orientation in micrometre-scale structures are experimentally challenging. Several research groups have suggested polarised Raman spectroscopy as a suitable technique for these measurements and have been able to partially characterise molecular orientations using one or two orientation parameters. Here we demonstrate a new approach that allows quantitative measurements of molecular orientations in terms of three parameters, offering the complete characterisation of a three-dimensional orientation. We apply this new method to organic semiconductor molecules in a single crystal field-effect transistor in order to correlate the measured orientation with charge carrier mobility measurements. This approach offers the opportunity for micrometre resolution (diffraction limited) spatial mapping of molecular orientation using bench-top apparatus, enabling a rational approach towards controlling this orientation to achieve optimum device performance.
Does cryptic microbiota mitigate pine resistance to an invasive beetle-fungus complex? Implications for invasion potential
Authors: Cheng Chihang , Xu Letian , Xu Dandan , Lou Qiaozhe , Lu Min , Sun Jianghua 
Published: September 2016

AbstractMicrobial symbionts are known to assist exotic pests in their colonization of new host plants. However, there has been little evidence linking symbiotic invasion success to mechanisms for mitigation of native plant resistance. The red turpentine beetle (RTB) was introduced with a fungus, Leptographium procerum, to China from the United States and became a destructively invasive symbiotic complex in natural Pinus tabuliformis forests. Here, we report that three Chinese-resident fungi, newly acquired by RTB in China, induce high levels of a phenolic defensive chemical, naringenin, in pines. This invasive beetle-fungus complex is suppressed by elevated levels of naringenin. However, cryptic microbiotas in RTB galleries strongly degrade naringenin, and pinitol, the main soluble carbohydrate of P. tabuliformis, is retained in L. procerum-infected phloem and facilitate naringenin biodegradation by the microbiotas. These results demonstrate that cryptic microbiota mitigates native host plant phenolic resistance to an invasive symbiotic complex, suggesting a putative mechanism for reduced biotic resistance to symbiotic invasion.
Incorporation of Eu(III) into Calcite under Recrystallization conditions
Authors: Hellebrandt S. E. , Hofmann S. , Jordan N. , Barkleit A. , Schmidt M. 
Published: September 2016

AbstractThe interaction of calcite with trivalent europium under recrystallization conditions was studied on the molecular level using site-selective time-resolved laser fluorescence spectroscopy (TRLFS). We conducted batch studies with a reaction time from seven days up to three years with three calcite powders, which differed in their specific surface area, recrystallization rates and impurities content. With increase of the recrystallization rate incorporation of Eu3+ occurs faster and its speciation comes to be dominated by one species with its excitation maximum at 578.8 nm, so far not identified during previous investigations of this process under growth and phase transformation conditions. A long lifetime of 3750 μs demonstrates complete loss of hydration, consequently Eu must have been incorporated into the bulk crystal. The results show a strong dependence of the incorporation kinetics on the recrystallization rate of the different calcites. Furthermore the investigation of the effect of different background electrolytes (NaCl and KCl) demonstrate that the incorporation process under recrystallization conditions strongly depends on the availability of Na+. These findings emphasize the different retention potential of calcite as a primary and secondary mineral e.g. in a nuclear waste disposal site.
Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile
Authors: Xia Kang , Zhan Haifei , Hu De’an , Gu Yuantong 
Published: September 2016

AbstractThe excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.
Cell wall degradation is required for normal starch mobilisation in barley endosperm
Authors: Andriotis Vasilios M. E. , Rejzek Martin , Barclay Elaine , Rugen Michael D. , Field Robert A. , Smith Alison M. 
Published: September 2016

AbstractStarch degradation in barley endosperm provides carbon for early seedling growth, but the control of this process is poorly understood. We investigated whether endosperm cell wall degradation is an important determinant of the rate of starch degradation. We identified iminosugar inhibitors of enzymes that degrade the cell wall component arabinoxylan. The iminosugar 1,4-dideoxy-1, 4-imino-l-arabinitol (LAB) inhibits arabinoxylan arabinofuranohydrolase (AXAH) but does not inhibit the main starch-degrading enzymes α- and β-amylase and limit dextrinase. AXAH activity in the endosperm appears soon after the onset of germination and resides in dimers putatively containing two isoforms, AXAH1 and AXAH2. Upon grain imbibition, mobilisation of arabinoxylan and starch spreads across the endosperm from the aleurone towards the crease. The front of arabinoxylan degradation precedes that of starch degradation. Incubation of grains with LAB decreases the rate of loss of both arabinoxylan and starch, and retards the spread of both degradation processes across the endosperm. We propose that starch degradation in the endosperm is dependent on cell wall degradation, which permeabilises the walls and thus permits rapid diffusion of amylolytic enzymes. AXAH may be of particular importance in this respect. These results provide new insights into the mobilization of endosperm reserves to support early seedling growth.