bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy
Authors: Borah A , Raveendran S , Rochani A , Maekawa T , Kumar D S 
Published: November 2015

AbstractExtensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.
Rational design of inorganic dielectric materials with expected permittivity
Authors: Xie Congwei , Oganov Artem R. , Dong Dong , Liu Ning , Li Duan , Debela Tekalign Terfa 
Published: November 2015

AbstractTechniques for rapid design of dielectric materials with appropriate permittivity for many important technological applications are urgently needed. It is found that functional structure blocks (FSBs) are helpful in rational design of inorganic dielectrics with expected permittivity. To achieve this, coordination polyhedra are parameterized as FSBs and a simple empirical model to evaluate permittivity based on these FSB parameters is proposed. Using this model, a wide range of examples including ferroelectric, high/low permittivity materials are discussed, resulting in several candidate materials for experimental follow-up.
Crystal structure of CobK reveals strand-swapping between Rossmann-fold domains and molecular basis of the reduced precorrin product trap
Authors: Gu Shuang , Sushko Oleksandr , Deery Evelyne , Warren Martin J. , Pickersgill Richard W. 
Published: November 2015

AbstractCobK catalyzes the essential reduction of the precorrin ring in the cobalamin biosynthetic pathway. The crystal structure of CobK reveals that the enzyme, despite not having the signature sequence, comprises two Rossmann fold domains which bind coenzyme and substrate respectively. The two parallel β-sheets have swapped their last β-strands giving a novel sheet topology which is an interesting variation on the Rossmann-fold. The trapped ternary complex with coenzyme and product reveals five conserved basic residues that bind the carboxylates of the tetrapyrrole tightly anchoring the product. A loop, disordered in both the apoenzyme and holoenzyme structures, closes around the product further tightening binding. The structure is consistent with a mechanism involving protonation of C18 and pro-R hydride transfer from NADPH to C19 of precorrin-6A and reveals the interactions responsible for the specificity of CobK. The almost complete burial of the reduced precorrin product suggests a remarkable form of metabolite channeling where the next enzyme in the biosynthetic pathway triggers product release.
Ternary SnS2–xSex Alloys Nanosheets and Nanosheet Assemblies with Tunable Chemical Compositions and Band Gaps for Photodetector Applications
Authors: Yu Jing , Xu Cheng-Yan , Li Yang , Zhou Fei , Chen Xiao-Shuang , Hu Ping-An , Zhen Liang 
Published: November 2015

AbstractTernary metal dichalcogenides alloys exhibit compositionally tunable optical properties and electronic structure and therefore, band gap engineering by controllable doping would provide a powerful approach to promote their physical and chemical properties. Herein we obtained ternary SnS2−xSexalloys with tunable chemical compositions and optical properties via a simple one-step solvothermal process. Raman scattering and UV-vis-NIR absorption spectra reveal the composition-related optical features and the band gaps can be discretely modulated from 2.23 to 1.29 eV with the increase of Se content. The variation tendency of band gap was also confirmed by first-principles calculations. The change of composition results in the difference of crystal structure as well as morphology for SnS2−xSexsolid solution, namely, nanosheets assemblies or nanosheet. The photoelectrochemical measurements indicate that the performance of ternary SnS2−xSexalloys depends on their band structures and morphology characteristics. Furthermore, SnS2−xSexphotodetectors present high photoresponsivity with a maximum of 35 mA W−1and good light stability in a wide range of spectral response from ultraviolet to visible light, which renders them promising candidates for a variety of optoelectronic applications.
Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI
Authors: Tarin Carlos , Carril Monica , Martin-Ventura Jose Luis , Markuerkiaga Irati , Padro Daniel , Llamas-Granda Patricia , Moreno Juan Antonio , García Isabel , Genicio Nuria , Plaza-Garcia Sandra , Blanco-Colio Luis Miguel , Penades Soledad , Egido Jesus 
Published: November 2015

AbstractCD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (−) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesions.
Structure of Mycobacterium thermoresistibile GlgE defines novel conformational states that contribute to the catalytic mechanism
Authors: Mendes Vitor , Blaszczyk Michal , Maranha Ana , Empadinhas Nuno , Blundell Tom L. 
Published: November 2015

AbstractGlgE, an enzyme of the pathway that converts trehalose to α-glucans, is essential for Mycobacterium tuberculosis. Inhibition of GlgE, which transfers maltose from a maltose-1-phosphate donor to α-glucan/maltooligosaccharide chain acceptor, leads to a toxic accumulation of maltose-1-phosphate that culminates in cellular death. Here we describe the first high-resolution mycobacterial GlgE structure from Mycobacterium thermoresistibile at 1.96 Å. We show that the structure resembles that of M. tuberculosis and Streptomyces coelicolor GlgEs, reported before, with each protomer in the homodimer comprising five domains. However, in M. thermoresistibile GlgE we observe several conformational states of the S domain and provide evidence that its high flexibility is important for enzyme activity. The structures here reported shed further light on the interactions between the N-terminal domains and the catalytic domains of opposing chains and how they contribute to the catalytic reaction. Importantly this work identifies a useful surrogate system to aid the development of GlgE inhibitors against opportunistic and pathogenic mycobacteria.
Effects of a discoloration-resistant calcium aluminosilicate cement on the viability and proliferation of undifferentiated human dental pulp stem cells
Authors: Niu Li-na , Watson Devon , Thames Kyle , Primus Carolyn M. , Bergeron Brian E. , Jiao Kai , Bortoluzzi Eduardo A. , Cutler Christopher W. , Chen Ji-hua , Pashley David H. , Tay Franklin R. 
Published: November 2015

AbstractDiscoloration-resistant calcium aluminosilicate cement has been formulated to overcome the timely problem of tooth discoloration reported in the clinical application of bismuth oxide-containing hydraulic cements. The present study examined the effects of this experimental cement (Quick-Set2) on the viability and proliferation of human dental pulp stem cells (hDPSCs) by comparing the cellular responses with commercially available calcium silicate cement (white mineral trioxide aggregate; WMTA) after different aging periods. Cell viability and proliferation were examined using assays that examined plasma membrane integrity, leakage of cytosolic enzyme, caspase-3 activity for early apoptosis, oxidative stress, mitochondrial metabolic activity and intracellular DNA content. Results of the six assays indicated that both Quick-Set2 and WMTA were initially cytotoxic to hDPSCs after setting for 24 h, with Quick-Set2 being comparatively less cytotoxic than WMTA at this stage. After two aging cycles, the cytotoxicity profiles of the two hydraulic cements were not significantly different and were much less cytotoxic than the positive control (zinc oxide–eugenol cement). Based on these results, it is envisaged that any potential beneficial effect of the discoloration-resistant calcium aluminosilicate cement on osteogenesis by differentiated hDPSCs is more likely to be revealed after outward diffusion and removal of its cytotoxic components.
M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production
Authors: Feng Jiaying , Gong Danyang , Fu Xudong , Wu Ting-ting , Wang Jane , Chang Jennifer , Zhou Jingting , Lu Gang , Wang Yibin , Sun Ren 
Published: November 2015

AbstractViruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.
CAP2 in cardiac conduction, sudden cardiac death and eye development
Authors: Field Jeffrey , Ye Diana Z. , Shinde Manasi , Liu Fang , Schillinger Kurt J. , Lu MinMin , Wang Tao , Skettini Michelle , Xiong Yao , Brice Angela K. , Chung Daniel C. , Patel Vickas V. 
Published: November 2015

AbstractSudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2−/cap2− males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2−/cap2− females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease.
Zeolite Nanoparticles for Selective Sorption of Plasma Proteins
Authors: Rahimi M. , Ng E.-P. , Bakhtiari K. , Vinciguerra M. , Ahmad H. Ali , Awala H. , Mintova S. , Daghighi M. , Bakhshandeh Rostami F. , de Vries M. , Motazacker M. M. , Peppelenbosch M. P. , Mahmoudi M. , Rezaee F. 
Published: November 2015

AbstractThe affinity of zeolite nanoparticles (diameter of 8–12 nm) possessing high surface area and high pore volume towards human plasma proteins has been investigated. The protein composition (corona) of zeolite nanoparticles has been shown to be more dependent on the plasma protein concentrations and the type of zeolites than zeolite nanoparticles concentration. The number of proteins present in the corona of zeolite nanoparticles at 100% plasma (in vivo state) is less than with 10% plasma exposure. This could be due to a competition between the proteins to occupy the corona of the zeolite nanoparticles. Moreover, a high selective adsorption for apolipoprotein C-III (APOC-III) and fibrinogen on the zeolite nanoparticles at high plasma concentration (100%) was observed. While the zeolite nanoparticles exposed to low plasma concentration (10%) exhibited a high selective adsorption for immunoglobulin gamma (i.e. IGHG1, IGHG2 and IGHG4) proteins. The zeolite nanoparticles can potentially be used for selectively capture of APOC-III in order to reduce the activation of lipoprotein lipase inhibition during hypertriglyceridemia treatment. The zeolite nanoparticles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX deficient)) with a risk of bleeding and thus might be potentially used in combination with the existing therapy.
A tool for determining duration of mortality events in archaeological assemblages using extant ungulate microwear
Authors: Rivals Florent , Prignano Luce , Semprebon Gina M. , Lozano Sergi 
Published: November 2015

AbstractThe seasonality of human occupations in archaeological sites is highly significant for the study of hominin behavioural ecology, in particular the hunting strategies for their main prey-ungulates. We propose a new tool to quantify such seasonality from tooth microwear patterns in a dataset of ten large samples of extant ungulates resulting from well-known mass mortality events. The tool is based on the combination of two measures of variability of scratch density, namely standard deviation and coefficient of variation. The integration of these two measurements of variability permits the classification of each case into one of the following three categories: (1) short events, (2) long-continued event and (3) two separated short events. The tool is tested on a selection of eleven fossil samples from five Palaeolithic localities in Western Europe which show a consistent classification in the three categories. The tool proposed here opens new doors to investigate seasonal patterns of ungulate accumulations in archaeological sites using non-destructive sampling.
Design of exceptionally strong and conductive Cu alloys beyond the conventional speculation via the interfacial energy-controlled dispersion of γ-Al2O3 nanoparticles
Authors: Zeon Han Seung , Kim Kwang Ho , Kang Joonhee , Joh Hongrae , Kim Sang Min , Ahn Jee Hyuk , Lee Jehyun , Lim Sung Hwan , Han Byungchan 
Published: November 2015

AbstractThe development of Cu-based alloys with high-mechanical properties (strength, ductility) and electrical conductivity plays a key role over a wide range of industrial applications. Successful design of the materials, however, has been rare due to the improvement of mutually exclusive properties as conventionally speculated. In this paper, we demonstrate that these contradictory material properties can be improved simultaneously if the interfacial energies of heterogeneous interfaces are carefully controlled. We uniformly disperse γ-Al2O3 nanoparticles over Cu matrix and then we controlled atomic level morphology of the interface γ-Al2O3//Cu by adding Ti solutes. It is shown that the Ti dramatically drives the interfacial phase transformation from very irregular to homogeneous spherical morphologies resulting in substantial enhancement of the mechanical property of Cu matrix. Furthermore, the Ti removes impurities (O and Al) in the Cu matrix by forming oxides leading to recovery of the electrical conductivity of pure Cu. We validate experimental results using TEM and EDX combined with first-principles density functional theory (DFT) calculations, which all consistently poise that our materials are suitable for industrial applications.
Isolation and Identification of Post-Transcriptional Gene Silencing-Related Micro-RNAs by Functionalized Silicon Nanowire Field-effect Transistor
Authors: Chen Kuan-I , Pan Chien-Yuan , Li Keng-Hui , Huang Ying-Chih , Lu Chia-Wei , Tang Chuan-Yi , Su Ya-Wen , Tseng Ling-Wei , Tseng Kun-Chang , Lin Chi-Yun , Chen Chii-Dong , Lin Shih-Shun , Chen Yit-Tsong 
Published: November 2015

AbstractMany transcribed RNAs are non-coding RNAs, including microRNAs (miRNAs), which bind to complementary sequences on messenger RNAs to regulate the translation efficacy. Therefore, identifying the miRNAs expressed in cells/organisms aids in understanding genetic control in cells/organisms. In this report, we determined the binding of oligonucleotides to a receptor-modified silicon nanowire field-effect transistor (SiNW-FET) by monitoring the changes in conductance of the SiNW-FET. We first modified a SiNW-FET with a DNA probe to directly and selectively detect the complementary miRNA in cell lysates. This SiNW-FET device has 7-fold higher sensitivity than reverse transcription-quantitative polymerase chain reaction in detecting the corresponding miRNA. Next, we anchored viral p19 proteins, which bind the double-strand small RNAs (ds-sRNAs), on the SiNW-FET. By perfusing the device with synthesized ds-sRNAs of different pairing statuses, the dissociation constants revealed that the nucleotides at the 3′-overhangs and pairings at the terminus are important for the interactions. After perfusing the total RNA mixture extracted from Nicotiana benthamiana across the device, this device could enrich the ds-sRNAs for sequence analysis. Finally, this bionanoelectronic SiNW-FET, which is able to isolate and identify the interacting protein-RNA, adds an additional tool in genomic technology for the future study of direct biomolecular interactions.
Porous VOxNy nanoribbons supported on CNTs as efficient and stable non-noble electrocatalysts for the oxygen reduction reaction
Authors: Huang K. , Bi K. , Lu Y. K. , Zhang R. , Liu J. , Wang W. J. , Tang H. L. , Wang Y. G. , Lei M. 
Published: November 2015

AbstractNovel nanocomposites of carbon nanotubes supported porous VOxNy nonoribbons (VOxNy-CNTs) have been synthesized by the annealing of the sol-gel mixture of CNTs and V2O5 under NH3 atmosphere as well as the ageing process in air. Besides the morphological and structural characterizations revealed by TEM, SEAD, EDS, XRD and XPS measurements, typical electrochemical tests including cyclic voltammetry (CV), rotating disk electrode (RDE) and chronoamperometry have been employed to determine the oxygen reduction reaction (ORR) performance of VOxNy-CNTs. Inspiringly, the results indicate that VOxNy-CNTs catalyst exhibits a 0.4 mA/cm2 larger diffusion-limited current density, a 0.10  V smaller onset potential value, a 10.73% less of ORR current decay and an excellent methanol-tolerance compared with commercial Pt/C catalyst. Therefore, we have reasonable grounds to believe that this new VOxNy-CNTs nanocomposites can be regarded as a promising non-precious methanol-tolerant ORR catalyst candidate for alkaline fuel cells.
An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand
Authors: Imwong Mallika , Jindakhad Thantip , Kunasol Chanon , Sutawong Kreepol , Vejakama Phisitt , Dondorp Arjen M. 
Published: November 2015

AbstractArtemisinin resistant falciparum malaria is an increasing problem in Southeast Asia, but has not been associated with increased transmission of the disease, yet. During a recent outbreak in 2014 in Ubon Ratchatani, Eastern Thailand, parasites from 101 patients with falciparum malaria were genotyped for antimalarial drug resistance markers. Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing. Resistance markers for antifolates and chloroquine were also highly prevalent. Most strains (91%) carried single copy number PfMDR1, suggesting sustained sensitivity to mefloquine, the partner drug in the local first-line artemisinin combination therapy (ACT). The high prevalence of artemisinin resistance in this recent malaria outbreak suggests but does not prove a causative role in increased transmission. Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.
Industrial arsenic contamination causes catastrophic changes in freshwater ecosystems
Authors: Chen Guangjie , Shi Haibin , Tao Jianshuang , Chen Li , Liu Yuanyuan , Lei Guoliang , Liu Xiaohai , Smol John P. 
Published: November 2015

AbstractHeavy metal pollution is now widely recognized to pose severe health and environmental threats, yet much of what is known concerning its adverse impacts on ecosystem health is derived from short-term ecotoxicological studies. Due to the frequent absence of long-term monitoring data, little is known of the long-tem ecological consequences of pollutants such as arsenic. Here, our dated sediment records from two contaminated lakes in China faithfully document a 13.9 and 21.4-fold increase of total arsenic relative to pre-1950 background levels. Concurrently, coherent responses in keystone biota signal pronounced ecosystem changes, with a >10-fold loss in crustacean zooplankton (important herbivores in the food webs of these lake systems) and a >5-fold increase in a highly metal-tolerant alga. Such fundamental ecological changes will cascade through the ecosystem, causing potentially catastrophic consequences for ecosystem services in contaminated regions.