bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2
Authors: Carter Megan , Jemth Ann-Sofie , Hagenkort Anna , Page Brent D. G. , Gustafsson Robert , Griese Julia J. , Gad Helge , Valerie Nicholas C. K. , Desroses Matthieu , Boström Johan , Warpman Berglund Ulrika , Helleday Thomas , Stenmark Pål 
Published: August 2015

AbstractDeregulated redox metabolism in cancer leads to oxidative damage to cellular components including deoxyribonucleoside triphosphates (dNTPs). Targeting dNTP pool sanitizing enzymes, such as MTH1, is a highly promising anticancer strategy. The MTH2 protein, known as NUDT15, is described as the second human homologue of bacterial MutT with 8-oxo-dGTPase activity. We present the first NUDT15 crystal structure and demonstrate that NUDT15 prefers other nucleotide substrates over 8-oxo-dGTP. Key structural features are identified that explain different substrate preferences for NUDT15 and MTH1. We find that depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT17 and NUDT18 were also profiled and found to have far less activity than MTH1 against oxidized nucleotides. We show that NUDT15 is not a biologically relevant 8-oxo-dGTPase, and that MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date.
Droplets move over viscoelastic substrates by surfing a ridge
Authors: Karpitschka S. , Das S. , van Gorcum M. , Perrin H. , Andreotti B. , Snoeijer J. H. 
Published: August 2015

AbstractLiquid drops on soft solids generate strong deformations below the contact line, resulting from a balance of capillary and elastic forces. The movement of these drops may cause strong, potentially singular dissipation in the soft solid. Here we show that a drop on a soft substrate moves by surfing a ridge: the initially flat solid surface is deformed into a sharp ridge whose orientation angle depends on the contact line velocity. We measure this angle for water on a silicone gel and develop a theory based on the substrate rheology. We quantitatively recover the dynamic contact angle and provide a mechanism for stick–slip motion when a drop is forced strongly: the contact line depins and slides down the wetting ridge, forming a new one after a transient. We anticipate that our theory will have implications in problems such as self-organization of cell tissues or the design of capillarity-based microrheometers.
Non-plasmonic nanoantennas for surface enhanced spectroscopies with ultra-low heat conversion
Authors: Caldarola Martín , Albella Pablo , Cortés Emiliano , Rahmani Mohsen , Roschuk Tyler , Grinblat Gustavo , Oulton Rupert F. , Bragas Andrea V. , Maier Stefan A. 
Published: August 2015

AbstractNanoplasmonics has recently revolutionized our ability to control light on the nanoscale. Using metallic nanostructures with tailored shapes, it is possible to efficiently focus light into nanoscale field ‘hot spots’. High field enhancement factors have been achieved in such optical nanoantennas, enabling transformative science in the areas of single molecule interactions, highly enhanced nonlinearities and nanoscale waveguiding. Unfortunately, these large enhancements come at the price of high optical losses due to absorption in the metal, severely limiting real-world applications. Via the realization of a novel nanophotonic platform based on dielectric nanostructures to form efficient nanoantennas with ultra-low light-into-heat conversion, here we demonstrate an approach that overcomes these limitations. We show that dimer-like silicon-based single nanoantennas produce both high surface enhanced fluorescence and surface enhanced Raman scattering, while at the same time generating a negligible temperature increase in their hot spots and surrounding environments.
Time reversal and charge conjugation in an embedding quantum simulator
Authors: Zhang Xiang , Shen Yangchao , Zhang Junhua , Casanova Jorge , Lamata Lucas , Solano Enrique , Yung Man-Hong , Zhang Jing-Ning , Kim Kihwan 
Published: August 2015

AbstractA quantum simulator is an important device that may soon outperform current classical computations. A basic arithmetic operation, the complex conjugate, however, is considered to be impossible to be implemented in such a quantum system due to the linear character of quantum mechanics. Here, we present the experimental quantum simulation of such an unphysical operation beyond the regime of unitary and dissipative evolutions through the embedding of a quantum dynamics in the electronic multilevels of a 171Yb+ ion. We perform time reversal and charge conjugation, which are paradigmatic examples of antiunitary symmetry operators, in the evolution of a Majorana equation without the tomographic knowledge of the evolving state. Thus, these operations can be applied regardless of the system size. Our approach offers the possibility to add unphysical operations to the toolbox of quantum simulation, and provides a route to efficiently compute otherwise intractable quantities, such as entanglement monotones.
A search for synergy in the binding kinetics of Trastuzumab and Pertuzumab whole and F(ab) to Her2
Authors: Lua Wai-Heng , Gan Samuel Ken-En , Lane David Philip , Verma Chandra Shekhar 
Published: August 2015

AbstractTherapeutic efficacy resulting from combining Trastuzumab and Pertuzumab in the treatment of Her2 overexpressing breast cancer patients has been shown to increase patient survival. This is thought to arise from inhibition of receptor dimerization and the immune tagging of the cancer cells; however, the underlying molecular mechanisms have remained enigmatic. Previously, a molecular modeling study suggested that this resulted from colocalization of the two antibodies on to the extracellular domain of Her2. We report here the experimental characterization of this interaction by measuring the binding kinetics of these two whole antibodies and their F(ab)s to the extracellular domain of Her2 in solution. We found that both antibodies (the whole antibodies and the fragments) colocalized on to Her2, but did not augment the binding of each other.
A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment
Authors: Fu Wei , Zhu Pengyu , Wang Chenguang , Huang Kunlun , Du Zhixin , Tian Wenying , Wang Qin , Wang Huiyu , Xu Wentao , Zhu Shuifang 
Published: August 2015

AbstractDigital PCR has developed rapidly since it was first reported in the 1990s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.
USP18 negatively regulates NF-κB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms
Authors: Yang Zhifen , Xian Huifang , Hu Jiajia , Tian Shuo , Qin Yunfei , Wang Rong-Fu , Cui Jun 
Published: August 2015

AbstractNuclear factor κB (NF-κB) is a key transcription factor in inflammatory immune responses and cell survival. Multiple types of ubiquitination play critical roles in the activation of NF-κB signaling, yet the molecular mechanisms responsible for their reversible deubiquitination are still poorly understood. In this study, we identified a member of the deubiquitinases family, ubiquitin-specific protease 18 (USP18), as a novel negative regulator in Toll-like receptor (TLR)-mediated NF-κB activation in human macrophages. USP18 is an interferon inducible gene, which is also upregulated by various TLR ligands in human monocytes and macrophages. Knockdown of USP18 enhanced the phosphorylation of IKK, the degradation of IκB and augmented the expression of pro-inflammatory cytokines. Furthermore, USP18 interacted with TAK1-TAB1 complex and IKKα/β-NEMO complex, respectively. USP18 cleaved the K63-linked polyubiquitin chains attached to TAK1 in a protease-dependent manner. Moreover, USP18 targeted the IKK complex through the regulatory subunit NEMO of IKK and specifically inhibited K63-linked ubiquitination of NEMO. Mutation analysis revealed direct binding of USP18 to the UBAN motif of NEMO. Our study has identified a previously unrecognized role for USP18 in the negative regulation of NF-κB activation by inhibiting K63-linked ubiquitination of TAK1 and NEMO through distinct mechanisms.
N-myc is a key switch regulating the proliferation cycle of postnatal cerebellar granule cell progenitors
Authors: Ma Ming , Wu Wenting , Li Qing , Li Jinya , Sheng Zhejin , Shi Jiahao , Zhang Mengjie , Yang Hua , Wang Zhugang , Sun Ruilin , Fei Jian 
Published: August 2015

AbstractN-myc plays an important role in early cerebellar development; however, the role of N-myc in postnatal cerebellar development is still unknown. In this study, inducible and reversible N-myc mouse models (NmycTRE/TRE:tTS and NmycEGFP/TRE:tTS) are used to regulate and track the expression of endogenous N-myc in vivo. Loss of N-myc at the neonatal stage results in reduced proliferation of granule cell precursors (GCPs) and reduced cerebellar volume/mass. Restoration of N-myc expression no later than postnatal day 4 can rescue the cerebellar developmental defect caused by the absence of N-myc after birth. During cerebellar postnatal development, N-myc acts as a key switch, regulating the proliferation cycle of postnatal granule cell progenitors. Loss of N-myc significantly impairs the Sonic hedgehog signalling pathway and disrupts the expression of cell cycle effectors with a significant reduction of Ccnd2. More importantly, N-myc negatively regulates the expression of microRNA-9 during postnatal cerebellar development. Our findings demonstrate that over-expression of miR-9 can inhibit the proliferation of GCPs. The regulation of these factors by N-myc is at least partly responsible for the switch role of N-myc in the proliferation cycle of GCPs.
Interface Engineering through Atomic Layer Deposition towards Highly Improved Performance of Dye-Sensitized Solar Cells
Authors: Lu Hao , Tian Wei , Guo Jun , Li Liang 
Published: August 2015

AbstractA composite photoanode comprising ultralong ZnO nanobelts and TiO2 nanoparticles was prepared and its performance in dye-sensitized solar cells (DSSCs) was optimized and compared to the photoanode consisting of conventional TiO2 nanoparticles. The ultralong ZnO nanobelts were synthesized in high yield by a facile solution approach at 90 oC followed by annealing at 500 oC. The effect of the ratio of ZnO nanobelts to TiO2 nanoparticles on the light scattering, specific surface area and interface recombination were investigated. An optimum amount of ZnO nanobelts enhanced the photon-conversion efficiency by 61.4% compared to that of the conventional TiO2 nanoparticles. To further reduce the recombination rate and increase the carrier lifetime, Atomic Layer Deposition (ALD) technique was utilized to coat a continuous TiO2 film surrounding the ZnO nanobelts and TiO2 nanoparticles, functioning as a barrier-free access of all electrons to conductive electrodes. This ALD treatment improved the interface contact within the whole photoanode system, finally leading to significant enhancement (137%) in the conversion efficiency of DSSCs.
HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response
Authors: Lim Key-Hwan , Park Jang-Joon , Gu Bon-Hee , Kim Jin-Ock , Park Sang Gyu , Baek Kwang-Hyun 
Published: August 2015

AbstractHAUSP (herpes virus-associated ubiquitin specific protease, known as ubiquitin specific protease 7), one of DUBs, regulates the dynamics of the p53 and Mdm2 network in response to DNA damage by deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Its concerted action increases the level of functional p53 by preventing proteasome-dependent degradation of p53. However, the protein substrates that are targeted by HAUSP to mediate DNA damage responses in the context of the HAUSP-p53-Mdm2 complex are not fully identified. Here, we identified nucleolin as a new substrate for HAUSP by proteomic analysis. Nucleolin has two HAUSP binding sites in its N- and C-terminal regions and the mutation of HAUSP interacting peptides on nucleolin disrupts their interaction and it leads to the increased level of nucleolin ubiquitination. In addition, HAUSP regulates the stability of nucleolin by removing ubiquitin from nucleolin. Nucleolin exists as a component of the HAUSP-p53-Mdm2 complex and both Mdm2 and p53 are required for the interaction between HAUSP and nucleolin. Importantly, the irradiation increases the HAUSP-nucleolin interaction, leading to nucleolin stabilization significantly. Taken together, this study reveals a new component of the HAUSP-p53-Mdm2 complex that governs dynamic cellular responses to DNA damage.
Sensitivity of mRNA Translation
Authors: Poker Gilad , Margaliot Michael , Tuller Tamir 
Published: August 2015

AbstractUsing the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, elongation and termination rates along the mRNA strand on the steady-state protein translation rate. We show that the sensitivity of mRNA translation is equal to the sensitivity of the maximal eigenvalue of a symmetric, nonnegative, tridiagonal and irreducible matrix. This leads to new analytical results as well as efficient numerical schemes that are applicable for large-scale models. Our results show that in the usual endogenous case, when initiation is more rate-limiting than elongation, the sensitivity of the translation rate to small mutations rapidly increases towards the 5′ end of the ORF. When the initiation rate is high, as may be the case for highly expressed and/or heterologous optimized genes, the maximal sensitivity is with respect to the elongation rates at the middle of the mRNA strand. We also show that the maximal possible effect of a small increase/decrease in any of the rates along the mRNA is an increase/decrease of the same magnitude in the translation rate. These results are in agreement with previous molecular evolutionary and synthetic biology experimental studies.
Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients
Authors: Ho Li-chun , Yen Chung-Jen , Chao Chia-Ter , Chiang Chih-Kang , Huang Jenq-Wen , Hung Kuan-Yu 
Published: August 2015

AbstractFactors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.
CACUL1/CAC1 Regulates the Antioxidant Response by Stabilizing Nrf2
Authors: Kigoshi Yu , Fukuda Tomomi , Endo Tomoyuki , Hayasaka Nami , Iemura Shun-ichiro , Natsume Toru , Tsuruta Fuminori , Chiba Tomoki 
Published: August 2015

AbstractNrf2 is the pre-dominant transcription activator responsible for coordinated up-regulation of ARE-driven antioxidant and detoxification genes. The activity of Nrf2 is tightly regulated at basal levels through its ubiquitination by Cul3-Keap1 and consequential degradation. Upon exposure to stress, the Cul3-Keap1 ligase is inhibited, leading to Nrf2 stabilization and activation. Here we describe CACUL1/CAC1 as a positive regulator of the Nrf2 pathway. We found that CACUL1 is up-regulated by Nrf2-activating oxidative stresses in cells and in mice. The association of CACUL1 with the Cul3-Keap1 complex led to a decrease in Nrf2 ubiquitination levels at non-stressed as well as stressed conditions and sensitized cells for higher Nrf2 activation. Furthermore, CACUL1 knock-down led to a decrease in Nrf2 activity and cell viability under stress. Our results show that CACUL1 is a regulator of Nrf2 ubiquitination, adding another regulatory layer to the Nrf2 antioxidant stress response.
A Surface-Enhanced Raman Scattering Sensor Integrated with Battery-Controlled Fluidic Device for Capture and Detection of Trace Small Molecules
Authors: Zhou Qitao , Meng Guowen , Zheng Peng , Cushing Scott , Wu Nianqiang , Huang Qing , Zhu Chuhong , Zhang Zhuo , Wang Zhiwei 
Published: August 2015

AbstractFor surface-enhanced Raman scattering (SERS) sensors, one of the important issues is the development of substrates not only with high SERS-activity but also with strong ability to capture analytes. However, it is difficult to achieve the two goals simultaneously especially when detecting small molecules. Herein a compact battery-controlled nanostructure-assembled SERS system has been demonstrated for capture and detection of trace small molecule pollutants in water. In this SERS fluidic system, an electrical heating constantan wire covered with the vertically aligned ZnO nanotapers decorated with Ag-nanoparticles is inserted into a glass capillary. A mixture of thermo-responsive microgels, Au-nanorods colloids and analyte solution is then filled into the remnant space of the capillary. When the system is heated by switching on the battery, the thermo-responsive microgels shrink, which immobilizes the analyte and drives the Au-nanorod close to each other and close to the Ag-ZnO nanotapers. This process has also created high-density “hot spots” due to multi-type plasmonic couplings in three-dimensional space, amplifying the SERS signal. This integrated device has been successfully used to measure methyl parathion in lake water, showing a great potential in detection of aquatic pollutants.
Measuring and mitigating agricultural greenhouse gas production in the US Great Plains, 1870–2000
Authors: Parton William J. , Gutmann Myron P. , Merchant Emily R. , Hartman Melannie D. , Adler Paul R. , McNeal Frederick M. , Lutz Susan M. 
Published: August 2015

Significance
The US Great Plains is an agricultural production center for the global market and a source of greenhouse gas (GHG) emissions. This article uses historical data and ecosystem models to estimate the magnitude of annual GHG fluxes from all agricultural sources (cropping, livestock, irrigation, fertilizer production, and tractor use) from 1870 to 2000. Carbon (C) emissions from plow-out of native grasslands peaked in the 1930s and were the largest agricultural source of GHG emissions at the time. Soil C emissions subsequently declined, whereas GHG fluxes from other activities increased. The results inform knowledge about the relationship between agriculture and its environmental setting and show that available alternative management practices could substantially mitigate the environmental consequences of agricultural activities without reducing food production.
Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily
Authors: McCulloch Kathryn M. , McCranie Emilianne K. , Smith Jarrod A. , Sarwar Maruf , Mathieu Jeannette L. , Gitschlag Bryan L. , Du Yu , Bachmann Brian O. , Iverson T. M. 
Published: August 2015

Significance
Bacterial resistance to clinically relevant antibiotics has renewed public interest in identifying therapeutics with new scaffolds for the treatment of such infections. Analogs of orthosomycins could provide one such scaffold. One route to modifying these scaffolds is through rational engineering of the biosynthetic enzymes, requiring characterization of the biosynthetic pathway. A key feature of orthosomycin antibiotics is the orthoester linkage between carbohydrate groups, and our data suggest that a family of oxygenases is likely responsible for orthoester formation.
Changing central Pacific El Niños reduce stability of North American salmon survival rates
Authors: Kilduff D. Patrick , Di Lorenzo Emanuele , Botsford Louis W. , Teo Steven L. H. 
Published: August 2015

Significance
Historically, many Pacific salmon species were thought to be influenced by the Pacific Decadal Oscillation (PDO), an indicator of ocean conditions, associated with El Niños. As the nature of El Niños has changed recently, another ocean indicator, the North Pacific Gyre Oscillation (NPGO) has become more important. By comparing time series, we find that coho and Chinook salmon survival rates along the west coast of North America are more strongly connected to the NPGO than the PDO. This was accompanied by increased similarity in survival rates of both species. Society seeks to maintain biodiversity among ecosystem components to provide a stable supply of ecosystem services through a portfolio effect. Increasingly similar salmon survivals implies reduced stability of these ecosystem services.
Spin-liquid polymorphism in a correlated electron system on the threshold of superconductivity
Authors: Zaliznyak Igor , Savici Andrei T. , Lumsden Mark , Tsvelik Alexei , Hu Rongwei , Petrovic Cedomir 
Published: August 2015

Significance
Liquid polymorphism and liquid–liquid phase transformations are remarkable phenomena of great fundamental and practical interest, as is unconventional superconductivity. Yet, despite being intensely studied, they still remain enigmatic. Our results not only provide a rare experimental example of liquid polymorphism, which occurs in the spin system of an iron chalcogenide superconductor, but also establish its unexpected connection with the onset of unconventional superconductivity.