bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branched-chain amino acids sustain pancreatic cancer growth by regulating lipid metabolism
Authors: Lee Ji Hyeon , Cho Young-ra , Kim Ji Hye , Kim Jongwook , Nam Hae Yun , Kim Seong Who , Son Jaekyoung 
Published: November 2019

AbstractBranched-chain amino acid (BCAA) catabolism and high levels of enzymes in the BCAA metabolic pathway have recently been shown to be associated with cancer growth and survival. However, the precise roles of BCAA metabolism in cancer growth and survival remain largely unclear. Here, we found that BCAA metabolism has an important role in human pancreatic ductal adenocarcinoma (PDAC) growth by regulating lipogenesis. Compared with nontransformed human pancreatic ductal (HPDE) cells, PDAC cells exhibited significantly elevated BCAA uptake through solute carrier transporters, which were highly upregulated in pancreatic tumor tissues compared with normal tissues. Branched-chain amino-acid transaminase 2 (BCAT2) knockdown markedly impaired PDAC cell proliferation, but not HPDE cell proliferation, without significant alterations in glutamate or reactive oxygen species levels. Furthermore, PDAC cell proliferation, but not HPDE cell proliferation, was substantially inhibited upon knockdown of branched-chain α-keto acid dehydrogenase a (BCKDHA). Interestingly, BCKDHA knockdown had no significant effect on mitochondrial metabolism; that is, neither the level of tricarboxylic acid cycle intermediates nor the oxygen consumption rate was affected. However, BCKDHA knockdown significantly inhibited fatty-acid synthesis, indicating that PDAC cells may utilize BCAAs as a carbon source for fatty-acid biosynthesis. Overall, our findings show that the BCAA metabolic pathway may provide a novel therapeutic target for pancreatic cancer.
Adaptive optics in laser processing
Authors: Salter Patrick S. , Booth Martin J. 
Published: November 2019

AbstractAdaptive optics are becoming a valuable tool for laser processing, providing enhanced functionality and flexibility for a range of systems. Using a single adaptive element, it is possible to correct for aberrations introduced when focusing inside the workpiece, tailor the focal intensity distribution for the particular fabrication task and/or provide parallelisation to reduce processing times. This is particularly promising for applications using ultrafast lasers for three-dimensional fabrication. We review recent developments in adaptive laser processing, including methods and applications, before discussing prospects for the future.
PCDH17 increases the sensitivity of colorectal cancer to 5-fluorouracil treatment by inducing apoptosis and autophagic cell death
Authors: Liu Shuiping , Lin Haoming , Wang Da , Li Qiang , Luo Hong , Li Guoxiong , Chen Xiaohui , Li Yongqiang , Chen Peng , Zhai Bingtao , Wang Wengang , Zhang Ruonan , Chen Bi , Zhang Mingming , Han Xuemeng , Li Qiujie , Chen Liuxi , Liu Ying , Chen Xiaying , Li Guohua , Xiang Yu , Duan Ting , Feng Jiao , Lou Jianshu , Huang Xingxing , Zhang Qin , Pan Ting , Yan Lili , Jin Ting , Zhang Wenzheng , Zhuo Lvjia , Sun Yitian , Xie Tian , Sui Xinbing 
Published: November 2019

Abstract5-Fluorouracil (5-FU) is known as a first-line chemotherapeutic agent against colorectal cancer (CRC), but drug resistance occurs frequently and significantly limits its clinical success. Our previous study showed that the protocadherin 17 (PCDH17) gene was frequently methylated and functioned as a tumor suppressor in CRC. However, the relationship between PCDH17 and 5-FU resistance in CRC remains unclear. Here, we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues, and high expression of PCDH17 was correlated with high BECN1 expression. Moreover, this expression profile contributed to superior prognosis and increased survival in CRC patients. Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death. Furthermore, autophagy played a dominant role in PCDH17-induced cell death, as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK. PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity. Mechanistically, we showed that c-Jun NH2-terminal kinase (JNK) activation was a key determinant in PCDH17-induced autophagy. The compound SP600125, an inhibitor of JNK, suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells. Taken together, our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death. PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients.
Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers
Authors: Tuna Musaffe , Ju Zhenlin , Yoshihara Kosuke , Amos Christopher I. , Tanyi Janos L. , Mills Gordon B. 
Published: November 2019

AbstractBackgroundMutation ofTP53is the most frequent genetic alteration in high-grade serous ovarian cancer (HGSOC). The impact of hotspot mutations ofTP53and protein levels on patient outcomes in HGSOC has not been fully elucidated.MethodsThe study population (n = 791) comprised of HGSOC samples withTP53mutation from TCGA and other publicly available data. Univariate and multivariate cox proportional hazards regression analyses were used to select variables that were correlated with patient survival.ResultsWe assessed the effects ofTP53mutations based on type and individual hotspot mutations on patient outcomes in HGSOC. Only hotspot mutations were associated with outcomes. Three hotspot mutations: G266, Y163C, and R282, in aggregate were associated with a worsened overall and recurrence-free survival compared with other hotspot mutations (p < 0.0001 andp = 0.001), other non-hotspot missense mutations (p < 0.0001 andp = 0.008), truncated mutations (p < 0.0001 andp = 0.001), and all other mutations (p < 0.0001 andp = 0.001). Specific hotspot mutations were associated with different protein expression patterns consistent with different functions.ConclusionsThis study provides evidence that individualTP53hotspot mutations have different impact on HGSOC patient outcomes and potentially TP53 function. Thus the status of particularTP53aberrations could influence response to therapy and selection of therapeutic agents.
Rebound of shelf water salinity in the Ross Sea
Authors: Castagno Pasquale , Capozzi Vincenzo , DiTullio Giacomo R. , Falco Pierpaolo , Fusco Giannetta , Rintoul Stephen R. , Spezie Giancarlo , Budillon Giorgio 
Published: November 2019

AbstractAntarctic Bottom Water (AABW) supplies the lower limb of the global overturning circulation and ventilates the abyssal ocean. In recent decades, AABW has warmed, freshened and reduced in volume. Ross Sea Bottom Water (RSBW), the second largest source of AABW, has experienced the largest freshening. Here we use 23 years of summer measurements to document temporal variability in the salinity of the Ross Sea High Salinity Shelf Water (HSSW), a precursor to RSBW. HSSW salinity decreased between 1995 and 2014, consistent with freshening observed between 1958 and 2008. However, HSSW salinity rebounded sharply after 2014, with values in 2018 similar to those observed in the mid-late 1990s. Near-synchronous interannual fluctuations in salinity observed at five locations on the continental shelf suggest that upstream preconditioning and large-scale forcing influence HSSW salinity. The rate, magnitude and duration of the recent salinity increase are unusual in the context of the (sparse) observational record.
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
Authors: Kobayashi Taeko , Piao Wenhui , Takamura Toshiya , Kori Hiroshi , Miyachi Hitoshi , Kitano Satsuki , Iwamoto Yumiko , Yamada Mayumi , Imayoshi Itaru , Shioda Seiji , Ballabio Andrea , Kageyama Ryoichiro 
Published: November 2019

AbstractQuiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricular zone of the mouse brain, but it remains largely unknown how lysosomal function is involved in the quiescence. Here we show that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs. Chemical inhibition of lysosomal degradation in qNSCs prevents degradation of signaling receptors resulting in exit from quiescence. Furthermore, conditional knockout of TFEB, a lysosomal master regulator, delays NSCs quiescence in vitro and increases NSC proliferation in the dentate gyrus of mice. Taken together, our results demonstrate that enhanced lysosomal degradation is an important regulator of qNSC maintenance.
Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET
Authors: Huynh Nhan , Ou Qiuxiang , Cox Pendleton , Lill Roland , King-Jones Kirst 
Published: November 2019

AbstractIron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.
Room-temperature quantum interference in single perovskite quantum dot junctions
Authors: Zheng Haining , Hou Songjun , Xin Chenguang , Wu Qingqing , Jiang Feng , Tan Zhibing , Zhou Xin , Lin Luchun , He Wenxiang , Li Qingmin , Zheng Jueting , Zhang Longyi , Liu Junyang , Yang Yang , Shi Jia , Zhang Xiaodan , Zhao Ying , Li Yuelong , Lambert Colin , Hong Wenjing 
Published: November 2019

AbstractThe studies of quantum interference effects through bulk perovskite materials at the Ångstrom scale still remain as a major challenge. Herein, we provide the observation of room-temperature quantum interference effects in metal halide perovskite quantum dots (QDs) using the mechanically controllable break junction technique. Single-QD conductance measurements reveal that there are multiple conductance peaks for the CH3NH3PbBr3 and CH3NH3PbBr2.15Cl0.85 QDs, whose displacement distributions match the lattice constant of QDs, suggesting that the gold electrodes slide through different lattice sites of the QD via Au-halogen coupling. We also observe a distinct conductance ‘jump’ at the end of the sliding process, which is further evidence that quantum interference effects dominate charge transport in these single-QD junctions. This conductance ‘jump’ is also confirmed by our theoretical calculations utilizing density functional theory combined with quantum transport theory. Our measurements and theory create a pathway to exploit quantum interference effects in quantum-controlled perovskite materials.
CRISPR-Switch regulates sgRNA activity by Cre recombination for sequential editing of two loci
Authors: Chylinski Krzysztof , Hubmann Maria , Hanna Ruth E. , Yanchus Connor , Michlits Georg , Uijttewaal Esther C. H. , Doench John , Schramek Daniel , Elling Ulrich 
Published: November 2019

AbstractCRISPR-Cas9 is an efficient and versatile tool for genome engineering in many species. However, inducible CRISPR-Cas9 editing systems that regulate Cas9 activity or sgRNA expression often suffer from significant limitations, including reduced editing capacity, off-target effects, or leaky expression. Here, we develop a precisely controlled sgRNA expression cassette that can be combined with widely-used Cre systems, termed CRISPR-Switch (SgRNA With Induction/Termination by Cre Homologous recombination). Switch-ON facilitates controlled, rapid induction of sgRNA activity. In turn, Switch-OFF-mediated termination of editing improves generation of heterozygous genotypes and can limit off-target effects. Furthermore, we design sequential CRISPR-Switch-based editing of two loci in a strictly programmable manner and determined the order of mutagenic events that leads to development of glioblastoma in mice. Thus, CRISPR-Switch substantially increases the versatility of gene editing through precise and rapid switching ON or OFF sgRNA activity, as well as switching OVER to secondary sgRNAs.
Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli
Authors: Amanatidou Elli , Matthews Andrew C. , Kuhlicke Ute , Neu Thomas R. , McEvoy James P. , Raymond Ben 
Published: November 2019

AbstractGram-negative bacteria such as Escherichia coli commonly resist β-lactam antibiotics using plasmid-encoded β-lactamase enzymes. Bacterial strains that express β-lactamases have been found to detoxify liquid cultures and thus to protect genetically susceptible strains, constituting a clear laboratory example of social protection. These results are not necessarily general; on solid media, for instance, the rapid bactericidal action of β-lactams largely prevents social protection. Here, we tested the hypothesis that the greater tolerance of biofilm bacteria for β-lactams would facilitate social interactions. We used a recently isolated E. coli strain, capable of strong biofilm formation, to compare how cooperation and exploitation in colony biofilms and broth culture drives the dynamics of a non-conjugative plasmid encoding a clinically important β-lactamase. Susceptible cells in biofilms were tolerant of ampicillin—high doses and several days of exposure were required to kill them. In support of our hypothesis, we found robust social protection of susceptible E. coli in biofilms, despite fine-scale physical separation of resistant and susceptible cells and lower rates of production of extracellular β-lactamase. In contrast, social interactions in broth were restricted to a relatively narrow range of ampicillin doses. Our results show that β-lactam selection pressure on Gram-negative biofilms leads to cooperative resistance characterized by a low equilibrium frequency of resistance plasmids, sufficient to protect all cells.
Systematic beyond-DFT study of binary transition metal oxides
Authors: Mandal Subhasish , Haule Kristjan , Rabe Karin M. , Vanderbilt David 
Published: November 2019

AbstractVarious methods going beyond density functional theory (DFT), such as DFT+U, hybrid functionals, meta-GGAs, GW, and DFT-embedded dynamical mean field theory (eDMFT), have been developed to describe the electronic structure of correlated materials, but it is unclear how accurate these methods can be expected to be when applied to a given strongly correlated solid. It is thus of pressing interest to compare their accuracy as they apply to different categories of materials. Here we introduce a novel paradigm in which a chosen set of beyond-DFT methods is systematically and uniformly tested on a chosen class of materials. For a first application, we choose the target materials to be the binary transition metal oxides FeO, CoO, MnO, and NiO in their antiferromagnetic phase and present a head-to-head comparison of spectral properties as computed using the various methods. We also compare with available experimental angle-resolved photoemission spectroscopy (ARPES), inverse-photoemission spectroscopy, and with optical absorption. For the class of compounds studied here, we find that both B3LYP and eDMFT reproduce the experiments quite well, with eDMFT doing best, in particular when comparing with the ARPES data.
Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats
Authors: Iyer Vishakh , Vo Quynh , Mell Anthony , Chinniah Siven , Zenerovitz Ashley , Venkiteswaran Kala , Kunselman Allen R. , Fang Jidong , Subramanian Thyagarajan 
Published: November 2019

AbstractRapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.
Local-measurement-based quantum state tomography via neural networks
Authors: Xin Tao , Lu Sirui , Cao Ningping , Anikeeva Galit , Lu Dawei , Li Jun , Long Guilu , Zeng Bei 
Published: November 2019

AbstractQuantum state tomography is a daunting challenge of experimental quantum computing, even in moderate system size. One way to boost the efficiency of state tomography is via local measurements on reduced density matrices, but the reconstruction of the full state thereafter is hard. Here, we present a machine-learning method to recover the ground states of $$k$$k-local Hamiltonians from just the local information, where a fully connected neural network is built to fulfill the task with up to seven qubits. In particular, we test the neural network model with a practical dataset, that in a 4-qubit nuclear magnetic resonance system our method yields global states via the 2-local information with high accuracy. Our work paves the way towards scalable state tomography in large quantum systems.
A global wildfire dataset for the analysis of fire regimes and fire behaviour
Authors: Artés Tomàs , Oom Duarte , de Rigo Daniele , Durrant Tracy Houston , Maianti Pieralberto , Libertà Giorgio , San-Miguel-Ayanz Jesús 
Published: November 2019

AbstractGlobal fire monitoring systems are crucial to study fire behaviour, fire regimes and their impact at the global scale. Although global fire products based on the use of Earth Observation satellites exist, most remote sensing products only partially cover the requirements for these analyses. These data do not provide information like fire size, fire spread speed, how fires may evolve and joint into single event, or the number of fire events for a given area. This high level of abstraction is very valuable; it makes it possible to characterize fires by types (either size, spread, behaviour, etc.). Here, we present and test a data mining work flow to create a global database of single fires that allows for the characterization of fire types and fire regimes worldwide. This work describes the data produced by a data mining process using MODIS burnt area product Collection 6 (MCD64A1). The entire product has been computed until the present and is available under the umbrella of the Global Wildfire Information System (GWIS).
Quantitative firing pattern phenotyping of hippocampal neuron types
Authors: Komendantov Alexander O. , Venkadesh Siva , Rees Christopher L. , Wheeler Diek W. , Hamilton David J. , Ascoli Giorgio A. 
Published: November 2019

AbstractSystematically organizing the anatomical, molecular, and physiological properties of cortical neurons is important for understanding their computational functions. Hippocampome.org defines 122 neuron types in the rodent hippocampal formation based on their somatic, axonal, and dendritic locations, putative excitatory/inhibitory outputs, molecular marker expression, and biophysical properties. We augmented the electrophysiological data of this knowledge base by collecting, quantifying, and analyzing the firing responses to depolarizing current injections for every hippocampal neuron type from published experiments. We designed and implemented objective protocols to classify firing patterns based on 5 transients (delay, adapting spiking, rapidly adapting spiking, transient stuttering, and transient slow-wave bursting) and 4 steady states (non-adapting spiking, persistent stuttering, persistent slow-wave bursting, and silence). This automated approach revealed 9 unique (plus one spurious) families of firing pattern phenotypes while distinguishing potential new neuronal subtypes. Novel statistical associations emerged between firing responses and other electrophysiological properties, morphological features, and molecular marker expression. The firing pattern parameters, experimental conditions, spike times, references to the original empirical evidences, and analysis scripts are released open-source through Hippocampome.org for all neuron types, greatly enhancing the existing search and browse capabilities. This information, collated online in human- and machine-accessible form, will help design and interpret both experiments and model simulations.
Translocation through a narrow pore under a pulling force
Authors: Niknam Hamidabad Mohammadreza , Haji Abdolvahab Rouhollah 
Published: November 2019

AbstractWe employ a three-dimensional molecular dynamics to simulate a driven polymer translocation through a nanopore by applying an external force, for four pore diameters and two external forces. To see the polymer and pore interaction effects on translocation time, we studied nine interaction energies. Moreover, to better understand the simulation results, we investigate polymer center of mass, shape factor and the monomer spatial distribution through the translocation process. Our results reveal that increasing the polymer-pore interaction energy is accompanied by an increase in the translocation time and decrease in the process rate. Furthermore, for pores with greater diameter, the translocation becomes faster. The shape analysis of the polymer indicates that the polymer shape is highly sensitive to the interaction energy. In great interactions, the monomers come close to the pore from both sides. As a result, the translocation becomes fast at first and slows down at last. Overall, it can be concluded that the external force does not play a major role in the shape and distribution of translocated monomers. However, the interaction energy between monomer and nanopore has a major effect especially on the distribution of translocated monomers on the trans side.