bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced ice sheet melting driven by volcanic eruptions during the last deglaciation
Authors: Muschitiello Francesco , Pausata Francesco S. R. , Lea James M. , Mair Douglas W. F. , Wohlfarth Barbara 
Published: October 2017

AbstractVolcanic eruptions can impact the mass balance of ice sheets through changes in climate and the radiative properties of the ice. Yet, empirical evidence highlighting the sensitivity of ancient ice sheets to volcanism is scarce. Here we present an exceptionally well-dated annual glacial varve chronology recording the melting history of the Fennoscandian Ice Sheet at the end of the last deglaciation (∼13,200–12,000 years ago). Our data indicate that abrupt ice melting events coincide with volcanogenic aerosol emissions recorded in Greenland ice cores. We suggest that enhanced ice sheet runoff is primarily associated with albedo effects due to deposition of ash sourced from high-latitude volcanic eruptions. Climate and snowpack mass-balance simulations show evidence for enhanced ice sheet runoff under volcanically forced conditions despite atmospheric cooling. The sensitivity of past ice sheets to volcanic ashfall highlights the need for an accurate coupling between atmosphere and ice sheet components in climate models.
LRRC25 Functions as an Inhibitor of NF-κB Signaling Pathway by Promoting p65/RelA for Autophagic Degradation
Authors: Feng Yanchun , Duan Tianhao , Du Yang , Jin Shouheng , Wang Mingjun , Cui Jun , Wang Rong-Fu 
Published: October 2017

AbstractNuclear factor κB (NF-κB) is a family of critical transcription factors that play a critical role in innate immune responses and inflammation, yet the molecular mechanisms responsible for its tight regulation is not fully understood. In this study, we identified LRRC25, a member of leucine-rich repeat (LRR)-containing protein family, as a negative regulator in the NF-κB signaling pathway. Ectopic expression of LRRC25 impaired NF-κB activation, whereas knockout of LRRC25 potentiated NF-κB activation and enhanced the production of inflammatory cytokines. Further study demonstrated that the LRR domain of LRRC25 interacted with the Rel Homology domain (RHD) of p65/RelA and promotes the degradation of p65/RelA. Furthermore, LRRC25 enhanced the interaction between p65/RelA and cargo receptor p62, thus facilitating the degradation of p65/RelA through autophagy pathway. Our study has not only identified LRRC25 as a novel inhibitor of NF-κB signaling pathway, but also uncovers a new mechanism of crosstalk between NF-κB signaling and autophagy pathways.
Unconventional two-dimensional vibrations of a decorated carbon nanotube under electric field: linking actuation to advanced sensing ability
Authors: de Aquino Belisa R. H. , Neek-Amal Mehdi , Milošević Milorad V. 
Published: October 2017

AbstractWe show that a carbon nanotube decorated with different types of charged metallic nanoparticles exhibits unusual two-dimensional vibrations when actuated by applied electric field. Such vibrations and diverse possible trajectories are not only fundamentally important but also have minimum two characteristic frequencies that can be directly linked back to the properties of the constituents in the considered nanoresonator. Namely, those frequencies and the maximal deflection during vibrations are very distinctively dependent on the geometry of the nanotube, the shape, element, mass and charge of the nanoparticle, and are vastly tunable by the applied electric field, revealing the unique sensing ability of devices made of molecular filaments and metallic nanoparticles.
Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage
Authors: Bačević Katarina , Lossaint Gérald , Achour Thiziri Nait , Georget Virginie , Fisher Daniel , Dulić Vjekoslav 
Published: October 2017

AbstractAlthough cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and promotes DNA replication, it is dispensable for cell cycle progression due to redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be revealed in certain genetic backgrounds and it was reported to promote the G2/M DNA damage response checkpoint in TP53 (p53)-deficient cancer cells. However, in p53-proficient cells subjected to DNA damage, Cdk2 is inactivated by the CDK inhibitor p21. We therefore investigated whether Cdk2 differentially affects checkpoint responses in p53-proficient and deficient cell lines. We show that, independently of p53 status, Cdk2 stimulates the ATR/Chk1 pathway and is required for an efficient DNA replication checkpoint response. In contrast, Cdk2 is not required for a sustained DNA damage response and G2 arrest. Rather, eliminating Cdk2 delays S/G2 progression after DNA damage and accelerates appearance of early markers of cell cycle exit. Notably, Cdk2 knockdown leads to down-regulation of Cdk6, which we show is a non-redundant pRb kinase whose elimination compromises cell cycle progression. Our data reinforce the notion that Cdk2 is a key p21 target in the DNA damage response whose inactivation promotes exit from the cell cycle in G2.
Metabolic syndrome in rats is associated with erectile dysfunction by impairing PI3K/Akt/eNOS activity
Authors: Li Rui , Cui Kai , Liu Kang , Li Hao , Zhang Yan , Liu Xiaming , Chen Ruibao , Li Mingchao , Wang Tao , Wang Shaogang , Liu Jihong , Rao Ke 
Published: October 2017

AbstractMetabolic syndrome (MetS) is a risk factor for erectile dysfunction (ED), but the underlying mechanisms are unclear. The aims of this study were to determine the underlying mechanisms of metabolic syndrome-related ED (MED). Sprague Dawley (SD) rats were fed a high-fat diet for 6 months, and metabolic parameters were then assessed. An apomorphine test was conducted to confirm MED. Only rats with MED were administered an intracavernosal injection of either epidermal growth factor (EGF) or vehicle for 4 weeks. Erectile responses were evaluated by determining the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP). Levels of protein expression were examined by western blotting and immunohistochemistry. Body weight, fasting blood glucose, plasma insulin and plasma total cholesterol were increased in the MetS rats compared with those in control rats (each﻿ p < 0.05). The maximum ICP/MAP, total ICP/MAP and concentration of cyclic guanosine mono-phosphate (cGMP) were significantly decreased in MED rats (each p < 0.05). The expression levels of p110α, p-Akt1 (Tyr308)/Akt1 and p-eNOS (Ser1177)/eNOS were reduced in MED rats (each p < 0.05). Activation of the PI3K/Akt/eNOS signaling cascade (intracavernosal injection of EGF) reversed these changes (each p < 0.05). The present study demonstrates that downregulation of the PI3K/Akt/eNOS signaling pathway is involved in MED.
The neonicotinoid insecticide Clothianidin adversely affects immune signaling in a human cell line
Authors: Di Prisco Gennaro , Iannaccone Marco , Ianniello Flora , Ferrara Rosalba , Caprio Emilio , Pennacchio Francesco , Capparelli Rosanna 
Published: October 2017

AbstractClothianidin is a widely used neonicotinoid insecticide, which is a potent agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic compound has a negative impact on insect immunity, as it down-regulates the activation of the transcription factor NF-κB. Given the evolutionary conserved role of NF-κB in the modulation of the immune response in the animal kingdom, here we want to assess any effect of Clothianidin on vertebrate defense barriers. In presence of this neonicotinoid insecticide, a pro-inflammatory challenge with LPS on the human monocytic cell line THP-1 results both in a reduced production of the cytokine TNF-α and in a down-regulation of a reporter gene under control of NF-κB promoter. This finding is corroborated by a significant impact of Clothianidin on the transcription levels of different immune genes, characterized by a core disruption of TRAF4 and TRAF6 that negatively influences NF-κB signaling. Moreover, exposure to Clothianidin concurrently induces a remarkable up-regulation of NGFR, which supports the occurrence of functional ties between the immune and nervous systems. These results suggest a potential risk of immunotoxicity that neonicotinoids may have on vertebrates, which needs to be carefully assessed at the organism level.
Effects of water availability on a forestry pathosystem: fungal strain-specific variation in disease severity
Authors: Linnakoski Riikka , Sugano Junko , Junttila Samuli , Pulkkinen Pertti , Asiegbu Fred O. , Forbes Kristian M. 
Published: October 2017

AbstractNorway spruce is one of the most important commercial forestry species in Europe, and is commonly infected by the bark beetle-vectored necrotrophic fungus, Endoconidiophora polonica. Spruce trees display a restricted capacity to respond to environmental perturbations, and we hypothesized that water limitation will increase disease severity in this pathosystem. To test this prediction, 737 seedlings were randomized to high (W+) or low (W−) water availability treatment groups, and experimentally inoculated with one of three E. polonica strains or mock-inoculated. Seedling mortality was monitored throughout an annual growing season, and total seedling growth and lesion length indices were measured at the experiment conclusion. Seedling growth was greater in the W+ than W− treatment group, demonstrating limitation due to water availability. For seedlings infected with two of the fungal strains, no differences in disease severity occurred in response to water availability. For the third fungal strain, however, greater disease severity (mortality and lesion lengths) occurred in W− than W+ seedlings. While the co-circulation in nature of multiple E. polonica strains of varying virulence is known, this is the first experimental evidence that water availability can alter strain-specific disease severity.
Laboratory cryo x-ray microscopy for 3D cell imaging
Authors: Fogelqvist Emelie , Kördel Mikael , Carannante Valentina , Önfelt Björn , Hertz Hans M. 
Published: October 2017

AbstractWater-window x-ray microscopy allows two- and three-dimensional (2D and 3D) imaging of intact unstained cells in their cryofixed near-native state with unique contrast and high resolution. Present operational biological water-window microscopes are based at synchrotron facilities, which limits their accessibility and integration with complementary methods. Laboratory-source microscopes have had difficulty addressing relevant biological tasks with proper resolution and contrast due to long exposure times and limited up-time. Here we report on laboratory cryo x-ray microscopy with the exposure time, contrast, and reliability to allow for routine high-spatial resolution 3D imaging of intact cells and cell-cell interactions. Stabilization of the laser-plasma source combined with new optics and sample preparation provide high-resolution cell imaging, both in 2D with ten-second exposures and in 3D with twenty-minute tomography. Examples include monitoring of the distribution of carbon-dense vesicles in starving HEK293T cells and imaging the interaction between natural killer cells and target cells.
Gem-diol and Ketone Crystal-to-crystal Transition Phenomena
Authors: Bo Zhang , Sitong Chen , Weiming Guo , Weijing Zhang , Lin Wang , Li Yang , Jianguo Zhang 
Published: October 2017

AbstractThe generally thought unstable diol compound tetrazyl gem-diol (1, H2DTMdiol·2H2O), was firstly obtained in crystalline form by culturing the filtrate for ten days after acidification and filtration of aqueous solution of potassium salt of ketone (2, [K(HDTMone)·2H2O]n). The stability of this novel gem-diol compound is found owning to the hydrogen bonds with lattice water molecules and electrophilic tetrazolyl groups. Meanwhile, the undissolved ketone (3, H2DTMone) was separated during the filtration in the process of gem-diol compound production. Surprisingly, the crystal-to-crystal perfect transition phenomena from gem-diol (1) to ketone (3) were firstly observed after heating up to 120 °C as evidenced by X-ray single crystal diffraction and powder X-ray diffraction. These results found here might open new revenues for methylene oxidation and alkanediol chemistry.
Cryo-EM Visualization of Lipid and Polymer-Stabilized Perfluorocarbon Gas Nanobubbles - A Step Towards Nanobubble Mediated Drug Delivery
Authors: Hernandez Christopher , Gulati Sahil , Fioravanti Gabriella , Stewart Phoebe L. , Exner Agata A. 
Published: October 2017

AbstractGas microbubbles stabilized with lipids, surfactants, proteins and/or polymers are widely used clinically as ultrasound contrast agents. Because of their large 1–10 µm size, applications of microbubbles are confined to the blood vessels. Accordingly, there is much interest in generating nanoscale echogenic bubbles (nanobubbles), which can enable new uses of ultrasound contrast agents in molecular imaging and drug delivery, particularly for cancer applications. While the interactions of microbubbles with ultrasound have been widely investigated, little is known about the activity of nanobubbles under ultrasound exposure. In this work, we demonstrate that cryo-electron microscopy (cryo-EM) can be used to image nanoscale lipid and polymer-stabilized perfluorocarbon gas bubbles before and after their destruction with high intensity ultrasound. In addition, cryo-EM can be used to observe electron-beam induced dissipation of nanobubble encapsulated perfluorocarbon gas.
Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels
Authors: Alaimo Alessandro , Nuñez Eider , Aivar Paloma , Fernández-Orth Juncal , Gomis-Perez Carolina , Bernardo-Seisdedos Ganeko , Malo Covadonga , Villarroel Alvaro 
Published: October 2017

AbstractTetrameric coiled-coil structures are present in many ion channels, often adjacent to a calmodulin (CaM) binding site, although the relationship between the two is not completely understood. Here we examine the dynamic properties of the ABCD domain located in the intracellular C-terminus of tetrameric, voltage-dependent, potassium selective Kv7.2 channels. This domain encompasses the CaM binding site formed by helices A and B, followed by helix C, which is linked to the helix D coiled-coil. The data reveals that helix D stabilizes CaM binding, promoting trans-binding (CaM embracing neighboring subunits), and they suggest that the ABCD domain can be exchanged between subunits of the tetramer. Exchange is faster when mutations in AB weaken the CaM interaction. The exchange of ABCD domains is slower in the presence of Ca2+, indicating that CaM stabilization of the tetrameric assembly is enhanced when loaded with this cation. Our observations are consistent with a model that involves a dynamic mechanism of helix D assembly, which supports reciprocal allosteric coupling between the A-B module and the coiled-coil formed by the helix D. Thus, formation of the distal helix D tetramer influences CaM binding and CaM-dependent Kv7.2 properties, whereas reciprocally, CaM and Ca2+ influence the dynamic behavior of the helix D coiled-coil.
Evaluating phenotype-driven approaches for genetic diagnoses from exomes in a clinical setting
Authors: Pengelly Reuben J. , Alom Thahmina , Zhang Zijian , Hunt David , Ennis Sarah , Collins Andrew 
Published: October 2017

AbstractNext generation sequencing is transforming clinical medicine and genome research, providing a powerful route to establishing molecular diagnoses for genetic conditions; however, challenges remain given the volume and complexity of genetic variation. A number of methods integrate patient phenotype and genotypic data to prioritise variants as potentially causal. Some methods have a clinical focus while others are more research-oriented. With clinical applications in mind we compare results from alternative methods using 21 exomes for which the disease causal variant has been previously established through traditional clinical evaluation. In this case series we find that the PhenIX program is the most effective, ranking the true causal variant at between 1 and 10 in 85% of these cases. This is a significantly higher proportion than the combined results from five alternative methods tested (p = 0.003). The next best method is Exomiser (hiPHIVE), in which the causal variant is ranked 1–10 in 25% of cases. The widely different targets of these methods (more clinical focus, considering known Mendelian genes, in PhenIX, versus gene discovery in Exomiser) is perhaps not fully appreciated but may impact strongly on their utility for molecular diagnosis using clinical exome data.
Identification of novel mazEF/pemIK family toxin-antitoxin loci and their distribution in the Staphylococcus genus
Authors: Bukowski Michal , Hyz Karolina , Janczak Monika , Hydzik Marcin , Dubin Grzegorz , Wladyka Benedykt 
Published: October 2017

AbstractThe versatile roles of toxin-antitoxin (TA) systems in bacterial physiology and pathogenesis have been investigated for more than three decades. Diverse TA loci in Bacteria and Archaea have been identified in genome-wide studies. The advent of massive parallel sequencing has substantially expanded the number of known bacterial genomic sequences over the last 5 years. In staphylococci, this has translated into an impressive increase from a few tens to a several thousands of available genomes, which has allowed us for the re-evalution of prior conclusions. In this study, we analysed the distribution of mazEF/pemIK family TA system operons in available staphylococcal genomes and their prevalence in mobile genetic elements. 10 novel mazEF/pemIK homologues were identified, each with a corresponding toxin that plays a potentially different and undetermined physiological role. A detailed characterisation of these TA systems would be exceptionally useful. Of particular interest are those associated with an SCCmec mobile genetic element (responsible for multidrug resistance transmission) or representing the joint horizontal transfer of TA systems and determinants of vancomycin resistance from enterococci. The involvement of TA systems in maintaining mobile genetic elements and the associations between novel mazEF/pemIK loci and those which carry drug resistance genes highlight their potential medical importance.
Phosphorylation regulates the subcellular localization of Cucumber Mosaic Virus 2b protein
Authors: Nemes Katalin , Gellért Ákos , Almási Asztéria , Vági Pál , Sáray Réka , Kádár Katalin , Salánki Katalin 
Published: October 2017

AbstractThe 2b protein of Cucumber mosaic virus has a role in nearly all steps of the viral cycle including cell-to-cell movement, symptom induction and suppression of antiviral RNA silencing. Previous studies demonstrated the presence of 2b protein in the nucleus and in cytoplasm as well. Phosphorylation site of 2b protein is conserved in all CMV isolates, including proposed constitute motifs for casein kinase II and cyclin-dependent kinase 2. To discern the impact of 2b protein phosphorylation, we created eight different mutants to mimic the non-phosporylated (serine to alanine) as well as the phosphorylated state (serine to aspartic acid) of the protein. We compared these mutants to the wild-type (Rs-CMV) virus in terms of symptom induction, gene silencing suppressor activity as well as in cellular localization. Here, in this study we confirmed the phosphorylation of 2b protein in vivo, both in infected N. benthamiana and in infiltrated patches. Mutants containing aspartic acid in the phosphorylation site accumulated only in the cytoplasm indicating that phosphorylated 2b protein could not enter the nucleus. We identified a conserved dual phosphorylation switch in CMV 2b protein, which equilibrates the shuttling of the 2b protein between the nucleus and the cytoplasm, and regulates the suppressor activity of the 2b protein.
A Novel β-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis
Authors: García-González Victor , Mas-Oliva Jaime 
Published: October 2017

AbstractOur study tested the proposal that c-Myc activation in macrophages is differentially carried out dependent on the intracellular oxidative state of cells and potentially associated to the process of atherogenesis. Under our experimental conditions, the generation of reactive oxygen species carried out by the presence of oxidized low density lipoproteins (oxLDL) or Gram negative bacterial lipopolysaccharides (LPS) modifies the expression of cellular adhesion molecules such as c-Abl, calcium transport proteins such as the plasma membrane Ca2+-ATPase (PMCA), CD47, procaspase-7, CASP7, CHOP, transcriptional activators such as c-Jun and c-Myc and molecules that participate in the process of endocytosis like α- and β-adaptin. We present the first evidence showing that a state of oxidative stress alters c-Myc-dependent activity pathways in macrophages through binding to molecules such as β-adaptin promoting the reversible formation of a complex that presents the ability to regulate the development of the cell cycle. We propose that the subtle regulation carried out through the formation of this c-Myc/β-adaptin complex when cells change from a normal physiological condition to a state of oxidative stress, represents a defense mechanism against the deleterious effects caused by the loss of cell homeostasis.
Direct Production of Furfural in One-pot Fashion from Raw Biomass Using Brønsted Acidic Ionic Liquids
Authors: Matsagar Babasaheb M. , Hossain Shahriar A. , Islam Tofazzal , Alamri Hatem R. , Alothman Zeid A. , Yamauchi Yusuke , Dhepe Paresh L. , Wu Kevin C.-W. 
Published: October 2017

AbstractThe conversion of raw biomass into C5-sugars and furfural was demonstrated with the one-pot method using Brønsted acidic ionic liquids (BAILs) without any mineral acids or metal halides. Various BAILs were synthesized and characterized using NMR, FT-IR, TGA, and CHNS microanalysis and were used as the catalyst for raw biomass conversion. The remarkably high yield (i.e. 88%) of C5 sugars from bagasse can be obtained using 1-methyl-3(3-sulfopropyl)-imidazolium hydrogen sulfate ([C3SO3HMIM][HSO4]) BAIL catalyst in a water medium. Similarly, the [C3SO3HMIM][HSO4] BAIL also converts the bagasse into furfural with very high yield (73%) in one-pot method using a water/toluene biphasic solvent system.
Long-term Intake of Pasta Containing Barley (1–3)Beta-D-Glucan Increases Neovascularization-mediated Cardioprotection through Endothelial Upregulation of Vascular Endothelial Growth Factor and Parkin
Authors: Casieri Valentina , Matteucci Marco , Cavallini Claudia , Torti Milena , Torelli Michele , Lionetti Vincenzo 
Published: October 2017

AbstractBarley (1–3)β-D-Glucan (BBG) enhances angiogenesis. Since pasta is very effective in providing a BBG-enriched diet, we hypothesized that the intake of pasta containing 3% BBG (P-BBG) induces neovascularization-mediated cardioprotection. Healthy adult male C57BL/6 mice fed P-BBG (n = 15) or wheat pasta (Control, n = 15) for five-weeks showed normal glucose tolerance and cardiac function. With a food intake similar to the Control, P-BBG mice showed a 109% survival rate (P < 0.01 vs. Control) after cardiac ischemia (30 min)/reperfusion (60 min) injury. Left ventricular (LV) anion superoxide production and infarct size in P-BBG mice were reduced by 62 and 35% (P < 0.0001 vs. Control), respectively. The capillary and arteriolar density of P-BBG hearts were respectively increased by 12 and 18% (P < 0.05 vs. Control). Compared to the Control group, the VEGF expression in P-BBG hearts was increased by 87.7% (P < 0.05); while, the p53 and Parkin expression was significantly increased by 125% and cleaved caspase-3 levels were reduced by 33% in P-BBG mice.In vitro, BBG was required to induce VEGF, p53 and Parkin expression in human umbelical vascular endothelial cells. Moreover, the BBG-induced Parkin expression was not affected by pifithrin-α (10 uM/7days), a p53 inhibitor. In conclusion, long-term dietary supplementation with P-BBG confers post-ischemic cardioprotection through endothelial upregulation of VEGF and Parkin.