bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Pore and Pore‐Throat Distributions in Controlling Permeability in Heterogeneous Mineral Dissolution and Precipitation Scenarios
Authors: Steinwinder Jeffrey , Beckingham Lauren E. 
Published: June 2019

AbstractMineral dissolution and precipitation reactions can significantly alter the porosity and permeability of porous media. While porosity generally increases with dissolution and decreases with precipitation, permeability is controlled by the spatial locations of reactions in discrete pores and pore throats and in the greater pore network. Geochemical reactions have been observed to occur both uniformly and nonuniformly in porous media, driven by parameters such as mineral distribution, grain size, and Peclet and Damkohler numbers. Pore network modeling can be used to simulate the impact of pore‐scale alterations on permeability, requiring only pore and pore‐throat size distributions and pore connectivity. Here, the impact of variations in pore and pore‐throat size distributions on reactive permeability for uniform and nonuniform spatial distributions of reactions is evaluated. A series of pore network models are created and populated with pore and pore‐throat size distributions of varying types (skewed, normal, and uniform) to represent differences in network topology and characterization methods. The impacts of these distributions on reactive permeability are then simulated for uniform and nonuniform reaction conditions by increasing or decreasing pore and pore‐throat sizes in a prescribed manner to reflect dissolution and precipitation, respectively. Overall, simulations reveal that porosity‐permeability evolution varies with reaction scenario and is qualitatively consistent for the different pore and pore‐throat size distributions. Common macroscopic porosity‐permeability relationships work well for some reaction scenarios but are unable to reflect size‐dependent reactions. A new modified version of the Verma‐Pruess relationship is created and able to successfully reflect the porosity‐permeability evolution for size‐dependent reactions.
Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation
Authors: Pan Haitao , Wang Yujie , Na Kun , Wang Ying , Wang Lu , Li Zhenhao , Guo Chengjie , Guo Dandan , Wang Xingya 
Published: June 2019

AbstractTargeting autophagy may serve as a promising strategy for cancer therapy. Ganoderma lucidum polysaccharide (GLP) has been shown to exert promising anti-cancer effects. However, the underlying mechanisms remain elusive. Whether GLP regulates autophagy in cancer has never been reported. In this study, GLP induced the initiation of autophagy in colorectal cancer (CRC) HT-29 and HCT116 cells, as evidenced by enhanced level of LC3-II protein, GFP-LC3 puncta, and increased formation of double membrane vacuoles. However, GLP treatment caused marked increase of p62 expression. Addition of late stage autophagy inhibitor, chloroquine (CQ), further enhanced LC3-II and p62 level, as well as increased autophagosome accumulation, suggesting a blockage of autophagic flux by GLP in CRC cells. We then found GLP blocked autophagosome and lysosome fusion as determined by mRFP-GFP-LC3 colocalization analysis. Mechanistic study revealed that GLP-induced disruption of autophagosome-lysosome fusion is due to reduced lysosome acidification and lysosomal cathepsin activities. Cell viability and flow cytometry assays revealed that GLP-induced autophagosome accumulation is responsible for GLP-induced apoptosis in CRC cells. In line with this, inhibition of autophagy initiation by 3-methyladenine (3-MA), an early stage autophagy inhibitor, attenuated GLP-induced apoptosis. In contrast, suppression of autophagy at late stage by CQ enhanced the anti-cancer effect of GLP. Furthermore, we demonstrated that GLP-induced autophagosome accumulation and apoptosis is mediated via MAPK/ERK activation. Finally, GLP inhibited tumor growth and also inhibited autophagic flux in vivo. These results unveil new molecular mechanism underlying anti-cancer effects of GLP, suggesting that GLP is a potent autophagy inhibitor and might be useful in anticancer therapy.
Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF/MCM7 complex
Authors: Wang Hai-Yang , Zhang Biao , Zhou Jun-Nian , Wang Dong-Xing , Xu Ying-Chen , Zeng Quan , Jia Ya-Li , Xi Jia-Fei , Nan Xue , He Li-Juan , Yue Wen , Pei Xue-Tao 
Published: June 2019

AbstractHepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (ATO), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including HCC. However, its anticancer mechanisms in HCC still need further investigation. In this study, we demonstrated that ATO inhibits tumorigenesis and distant metastasis in mouse models, corresponding with a prolonged mice survival time. Also, ATO was found to significantly decrease the cancer stem cell (CSC)-associated traits. Minichromosome maintenance protein (MCM) 7 was further identified to be a potential target suppressed dramatically by ATO, of which protein expression is increased in patients and significantly correlated with tumor size, cellular differentiation, portal venous emboli, and poor patient survival. Moreover, MCM7 knockdown recapitulates the effects of ATO on CSCs and metastasis, while ectopic expression of MCM7 abolishes them. Mechanistically, our results suggested that ATO suppresses MCM7 transcription by targeting serum response factor (SRF)/MCM7 complex, which functions as an important transcriptional regulator modulating MCM7 expression. Taken together, our findings highlight the importance of ATO in the treatment of solid tumors. The identification of SRF/MCM7 complex as a target of ATO provides new insights into ATO’s mechanism, which may benefit the appropriate use of this agent in the treatment of HCC.
Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation
Authors: Sajini Abdulrahim A. , Choudhury Nila Roy , Wagner Rebecca E. , Bornelöv Susanne , Selmi Tommaso , Spanos Christos , Dietmann Sabine , Rappsilber Juri , Michlewski Gracjan , Frye Michaela 
Published: June 2019

AbstractThe presence and absence of RNA modifications regulates RNA metabolism by modulating the binding of writer, reader, and eraser proteins. For 5-methylcytosine (m5C) however, it is largely unknown how it recruits or repels RNA-binding proteins. Here, we decipher the consequences of m5C deposition into the abundant non-coding vault RNA VTRNA1.1. Methylation of cytosine 69 in VTRNA1.1 occurs frequently in human cells, is exclusively mediated by NSUN2, and determines the processing of VTRNA1.1 into small-vault RNAs (svRNAs). We identify the serine/arginine rich splicing factor 2 (SRSF2) as a novel VTRNA1.1-binding protein that counteracts VTRNA1.1 processing by binding the non-methylated form with higher affinity. Both NSUN2 and SRSF2 orchestrate the production of distinct svRNAs. Finally, we discover a functional role of svRNAs in regulating the epidermal differentiation programme. Thus, our data reveal a direct role for m5C in the processing of VTRNA1.1 that involves SRSF2 and is crucial for efficient cellular differentiation.
LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy
Authors: Pascual-García Mónica , Bonfill-Teixidor Ester , Planas-Rigol Ester , Rubio-Perez Carlota , Iurlaro Raffaella , Arias Alexandra , Cuartas Isabel , Sala-Hojman Ada , Escudero Laura , Martínez-Ricarte Francisco , Huber-Ruano Isabel , Nuciforo Paolo , Pedrosa Leire , Marques Carolina , Braña Irene , Garralda Elena , Vieito María , Squatrito Massimo , Pineda Estela , Graus Francesc , Espejo Carmen , Sahuquillo Juan , Tabernero Josep , Seoane Joan 
Published: June 2019

AbstractCancer response to immunotherapy depends on the infiltration of CD8+ T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8+ T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8+ T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival.
Record of low-temperature aqueous alteration of Martian zircon during the late Amazonian
Authors: Guitreau Martin , Flahaut Jessica 
Published: June 2019

AbstractSeveral lines of evidence support the presence of liquid water on Mars at different times. Among those, hydrated minerals testify to past aqueous weathering processes that can be precisely studied in Martian meteorites such as NWA 7533/7034. Bringing constraints on the timing of weathering of the Martian crust would help understand its evolution, the availability of liquid water, and the habitability of Mars. Here we present a new method based on U–Th–Pb isotope systems to assess if zircon crystals underwent low-temperature aqueous alteration, such as exemplified by Hadean-aged detrital crystals from Western Australia. Data for NWA 7533 zircons show evidence for aqueous alteration and modeling of U–Th–Pb isotope system evolution indicates that the latest alteration event occurred during the late Amazonian (227–56 Ma). This finding largely expands the time duration over which liquid water was available near the Martian surface, thereby suggesting that Mars might still be habitable.
Fast and selective fluoride ion conduction in sub-1-nanometer metal-organic framework channels
Authors: Li Xingya , Zhang Huacheng , Wang Peiyao , Hou Jue , Lu Jun , Easton Christopher D. , Zhang Xiwang , Hill Matthew R. , Thornton Aaron W. , Liu Jefferson Zhe , Freeman Benny D. , Hill Anita J. , Jiang Lei , Wang Huanting 
Published: June 2019

AbstractBiological fluoride ion channels are sub-1-nanometer protein pores with ultrahigh F− conductivity and selectivity over other halogen ions. Developing synthetic F− channels with biological-level selectivity is highly desirable for ion separations such as water defluoridation, but it remains a great challenge. Here we report synthetic F− channels fabricated from zirconium-based metal-organic frameworks (MOFs), UiO-66-X (X = H, NH2, and N+(CH3)3). These MOFs are comprised of nanometer-sized cavities connected by sub-1-nanometer-sized windows and have specific F− binding sites along the channels, sharing some features of biological F− channels. UiO-66-X channels consistently show ultrahigh F− conductivity up to ~10 S m−1, and ultrahigh F−/Cl− selectivity, from ~13 to ~240. Molecular dynamics simulations reveal that the ultrahigh F− conductivity and selectivity can be ascribed mainly to the high F− concentration in the UiO-66 channels, arising from specific interactions between F− ions and F− binding sites in the MOF channels.
A mechanism to prevent production of reactive oxygen species by Escherichia coli respiratory complex I
Authors: Schulte Marius , Frick Klaudia , Gnandt Emmanuel , Jurkovic Sascha , Burschel Sabrina , Labatzke Ramona , Aierstock Karoline , Fiegen Dennis , Wohlwend Daniel , Gerhardt Stefan , Einsle Oliver , Friedrich Thorsten 
Published: June 2019

AbstractRespiratory complex I plays a central role in cellular energy metabolism coupling NADH oxidation to proton translocation. In humans its dysfunction is associated with degenerative diseases. Here we report the structure of the electron input part of Aquifex aeolicus complex I at up to 1.8 Å resolution with bound substrates in the reduced and oxidized states. The redox states differ by the flip of a peptide bond close to the NADH binding site. The orientation of this peptide bond is determined by the reduction state of the nearby [Fe-S] cluster N1a. Fixation of the peptide bond by site-directed mutagenesis led to an inactivation of electron transfer and a decreased reactive oxygen species (ROS) production. We suggest the redox-gated peptide flip to represent a previously unrecognized molecular switch synchronizing NADH oxidation in response to the redox state of the complex as part of an intramolecular feed-back mechanism to prevent ROS production.
Functional traits and phenotypic plasticity modulate species coexistence across contrasting climatic conditions
Authors: Pérez-Ramos Ignacio M. , Matías Luis , Gómez-Aparicio Lorena , Godoy Óscar 
Published: June 2019

AbstractFunctional traits are expected to modulate plant competitive dynamics. However, how traits and their plasticity in response to contrasting environments connect with the mechanisms determining species coexistence remains poorly understood. Here, we couple field experiments under two contrasting climatic conditions to a plant population model describing competitive dynamics between 10 annual plant species in order to evaluate how 19 functional traits, covering physiological, morphological and reproductive characteristics, are associated with species’ niche and fitness differences. We find a rich diversity of univariate and multidimensional associations, which highlight the primary role of traits related to water- and light-use-efficiency for modulating the determinants of competitive outcomes. Importantly, such traits and their plasticity promote species coexistence across climatic conditions by enhancing stabilizing niche differences and by generating competitive trade-offs between species. Our study represents a significant advance showing how leading dimensions of plant function connect to the mechanisms determining the maintenance of biodiversity.
LUX ARRHYTHMO mediates crosstalk between the circadian clock and defense in Arabidopsis
Authors: Zhang Chong , Gao Min , Seitz Nicholas C. , Angel William , Hallworth Amelia , Wiratan Linda , Darwish Omar , Alkharouf Nadim , Dawit Teklu , Lin Daniela , Egoshi Riki , Wang Xiping , McClung C. Robertson , Lu Hua 
Published: June 2019

AbstractThe circadian clock is known to regulate plant innate immunity but the underlying mechanism of this regulation remains largely unclear. We show here that mutations in the core clock component LUX ARRHYTHMO (LUX) disrupt circadian regulation of stomata under free running andPseudomonassyringaechallenge conditions as well as defense signaling mediated by SA and JA, leading to compromised disease resistance. RNA-seq analysis reveals that both clock- and defense-related genes are regulated by LUX. LUX binds to clock gene promoters that have not been shown before, expanding the clock gene networks that require LUX function. LUX also binds to the promoters ofEDS1andJAZ5, likely acting through these genes to affect SA- and JA-signaling. We further show that JA signaling reciprocally affects clock activity. Thus, our data support crosstalk between the circadian clock and plant innate immunity and imply an important role ofLUXin this process.
In situ observations of an active MoS2 model hydrodesulfurization catalyst
Authors: Mom Rik V. , Louwen Jaap N. , Frenken Joost W. M. , Groot Irene M. N. 
Published: June 2019

AbstractThe hydrodesulfurization process is one of the cornerstones of the chemical industry, removing harmful sulfur from oil to produce clean hydrocarbons. The reaction is catalyzed by the edges of MoS2 nanoislands and is operated in hydrogen-oil mixtures at 5–160 bar and 260–380 °C. Until now, it has remained unclear how these harsh conditions affect the structure of the catalyst. Using a special-purpose high-pressure scanning tunneling microscope, we provide direct observations of an active MoS2 model catalyst under reaction conditions. We show that the active edge sites adapt their sulfur, hydrogen, and hydrocarbon coverages depending on the gas environment. By comparing these observations to density functional theory calculations, we propose that the dominant edge structure during the desulfurization of CH3SH contains a mixture of adsorbed sulfur and CH3SH.
Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts
Authors: Daszynski Damian M. , Santhoshkumar Puttur , Phadte Ashutosh S. , Sharma K. Krishna , Zhong Haizhen A. , Lou Marjorie F. , Kador Peter F. 
Published: June 2019

AbstractThe paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to αB-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses cultured for 48 hours in TC-199 bicarbonate media through physical trauma, 10 mM ouabain as Na+/K+ ATPase ion transport inhibitor, or 1 mM of an experimental compound that induces water influx into the lens. Subsequent 48-hour incubation with 15 mM of lanosterol liposomes failed to either reverse these lens opacities or prevent the further progression of cataracts to the nuclear stage. Similarly, 3-day incubation of 47-year old human lenses in media containing 0.20 mM lanosterol or 60-year-old human lenses in 0.25 and 0.50 mM 25-hydroxycholesterol failed to increase the levels of soluble lens proteins or decrease the levels of insoluble lens proteins. These binding studies were followed up with in silico binding studies of lanosterol, 25-hydroxycholesterol, and ATP as a control to two wild type (2WJ7 and 2KLR) and one R120G mutant (2Y1Z) αB-crystallins using standard MOETM (Molecular Operating Environment) and Schrödinger’s Maestro software. Results confirmed that compared to ATP, both oxysterols failed to reach the acceptable threshold binding scores for good predictive binding to the αB-crystallins. In summary, all three studies failed to provide evidence that lanosterol or 25-hydroxycholesterol have either anti-cataractogenic activity or bind aggregated lens protein to dissolve cataracts.
Amaryllidaceae alkaloids: identification and partial characterization of montanine production in Rhodophiala bifida plant
Authors: Reis Andressa , Magne Kevin , Massot Sophie , Tallini Luciana R. , Scopel Marina , Bastida Jaume , Ratet Pascal , Zuanazzi José A. S. 
Published: June 2019

AbstractRhodophiala bifida (R. bifida) is a representative of the Amaryllidaceae plant family and is rich in montanine, an alkaloid with high pharmaceutical potential. Despite the interest in these compounds, many steps of the biosynthetic pathway have not been elucidated. In this study, we identified the alkaloids produced in different organs of R. bifida under different growth conditions, set up the conditions for in vitro R. bifida regeneration and initiated the molecular characterization of two R. bifida genes involved in alkaloids biosynthesis: the Norbelladine 4′-O-Methyltransferase (RbN4OMT) and the Cytochrome P450 (RbCYP96T). We show that montanine is the main alkaloid produced in the different R. bifida organs and developed a direct organogenesis regeneration protocol, using twin-scale explants cultivated on media enriched with naphthalene acetic acid and benzyladenine. Finally, we analyzed the RbN4OMT and RbCYP96T gene expressions in different organs and culture conditions and compared them to alkaloid production. In different organs of R. bifida young, adult and regenerated plants, as well as under various growing conditions, the transcripts accumulation was correlated with the production of alkaloids. This work provides new tools to improve the production of this important pharmaceutical compound and for future biotechnological studies.
First crystal structure of an endo-levanase – the BT1760 from a human gut commensal Bacteroides thetaiotaomicron
Authors: Ernits Karin , Eek Priit , Lukk Tiit , Visnapuu Triinu , Alamäe Tiina 
Published: June 2019

AbstractThe endo-levanase BT1760 of a human gut commensal Bacteroides thetaiotaomicron randomly cuts a β-2,6-linked fructan, levan, into fructo-oligosaccharides providing a prebiotic substrate for gut microbiota. Here we introduce the crystal structure of BT1760 at resolution of 1.65 Å. The fold of the enzyme is typical for GH32 family proteins: a catalytic N-terminal five-bladed β-propeller connected with a C-terminal β-sandwich domain. The levantetraose-bound structure of catalytically inactive mutant E221A at 1.90-Å resolution reveals differences in substrate binding between the endo-acting fructanases. A shallow substrate-binding pocket of the endo-inulinase INU2 of Aspergillus ficuum binds at least three fructose residues at its flat bottom. In the levantetraose-soaked crystal of the endo-levanase E221A mutant the ligand was bent into the pond-like substrate pocket with its fructose residues making contacts at −3, −2, −1 and + 1 subsites residing at several pocket depths. Binding of levantetraose to the β-sandwich domain was not detected. The N- and C-terminal modules of BT1760 did not bind levan if expressed separately, the catalytic domain lost its activity and both modules tended to precipitate. We gather that endo-levanase BT1760 requires both domains for correct folding, solubility and stability of the protein.
Nanosecond pulsed electric fields induce extracellular release of chromosomal DNA and histone citrullination in neutrophil-differentiated HL-60 cells
Authors: Koga Tsubasa , Morotomi-Yano Keiko , Sakugawa Takashi , Saitoh Hisato , Yano Ken-ichi 
Published: June 2019

AbstractNanosecond pulsed electric fields (nsPEFs) have gained attention as a novel physical stimulus for life sciences. Although cancer therapy is currently their promising application, nsPEFs have further potential owing to their ability to elicit various cellular responses. This study aimed to explore stimulatory actions of nsPEFs, and we used HL-60 cells that were differentiated into neutrophils under cultured conditions. Exposure of neutrophil-differentiated HL-60 cells to nsPEFs led to the extracellular release of chromosomal DNA, which appears to be equivalent to neutrophil extracellular traps (NETs) that serve as a host defense mechanism against pathogens. Fluorometric measurement of extracellular DNA showed that DNA extrusion was rapidly induced after nsPEF exposure and increased over time. Western blot analysis demonstrated that nsPEFs induced histone citrullination that is the hydrolytic conversion of arginine to citrulline on histones and facilitates chromatin decondensation. DNA extrusion and histone citrullination by nsPEFs were cell type-specific and Ca2+-dependent events. Taken together, these observations suggest that nsPEFs drive the mechanism for neutrophil-specific immune response without infection, highlighting a novel aspect of nsPEFs as a physical stimulus.