bluuebunny/crossref_metadata_2025_split huggingface dataset:
Snail modulates JNK-mediated cell death in Drosophila
Authors: Wu Chenxi , Li Zhuojie , Ding Xiang , Guo Xiaowei , Sun Ying , Wang Xingjun , Hu Yujia , Li Tongtong , La Xiaojin , Li Jianing , Li Ji-an , Li Wenzhe , Xue Lei 
Published: November 2019

AbstractCell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.
Contribution of apical and basal dendrites to orientation encoding in mouse V1 L2/3 pyramidal neurons
Authors: Park Jiyoung , Papoutsi Athanasia , Ash Ryan T. , Marin Miguel A. , Poirazi Panayiota , Smirnakis Stelios M. 
Published: November 2019

AbstractPyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input.
Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma
Authors: Zhang Shuang , Dolgalev Igor , Zhang Tao , Ran Hao , Levine Douglas A. , Neel Benjamin G. 
Published: November 2019

AbstractThe cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8 + FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidly to the ovarian surface. These events were recapitulated by orthotopic injection of mutant FTE organoids. Engineering the same genetic lesions into Lgr5 + OSE or OSE-derived organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. FTE- and OSE-derived tumors had distinct transcriptomes, and comparative transcriptomics and genomics suggest that human HGSOC arises from both cell types. Finally, FTE- and OSE-derived organoids exhibited differential chemosensitivity. Our results comport with a dualistic origin for HGSOC and suggest that the cell-of-origin might influence therapeutic response.
Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories
Authors: Das Ravi K. , Gale Grace , Walsh Katie , Hennessy Vanessa E. , Iskandar Georges , Mordecai Luke A. , Brandner Brigitta , Kindt Merel , Curran H. Valerie , Kamboj Sunjeev K. 
Published: November 2019

AbstractMaladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical ‘reconsolidation window’ predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.
Flexible and durable wood-based triboelectric nanogenerators for self-powered sensing in athletic big data analytics
Authors: Luo Jianjun , Wang Ziming , Xu Liang , Wang Aurelia Chi , Han Kai , Jiang Tao , Lai Qingsong , Bai Yu , Tang Wei , Fan Feng Ru , Wang Zhong Lin 
Published: November 2019

AbstractIn the new era of internet of things, big data collection and analysis based on widely distributed intelligent sensing technology is particularly important. Here, we report a flexible and durable wood-based triboelectric nanogenerator for self-powered sensing in athletic big data analytics. Based on a simple and effective strategy, natural wood can be converted into a high-performance triboelectric material with excellent mechanical properties, such as 7.5-fold enhancement in strength, superior flexibility, wear resistance and processability. The electrical output performance is also enhanced by more than 70% compared with natural wood. A self-powered falling point distribution statistical system and an edge ball judgement system are further developed to provide training guidance and real-time competition assistance for both athletes and referees. This work can not only expand the application area of the self-powered system to smart sport monitoring and assisting, but also promote the development of big data analytics in intelligent sports industry.
On-target restoration of a split T cell-engaging antibody for precision immunotherapy
Authors: Banaszek Agnes , Bumm Thomas G. P. , Nowotny Boris , Geis Maria , Jacob Kim , Wölfl Matthias , Trebing Johannes , Kucka Kirstin , Kouhestani Dina , Gogishvili Tea , Krenz Bastian , Lutz Justina , Rasche Leo , Hönemann Dirk , Neuweiler Hannes , Heiby Julia C. , Bargou Ralf C. , Wajant Harald , Einsele Hermann , Riethmüller Gert , Stuhler Gernot 
Published: November 2019

AbstractT cell-engaging immunotherapies are changing the landscape of current cancer care. However, suitable target antigens are scarce, restricting these strategies to very few tumor types. Here, we report on a T cell-engaging antibody derivative that comes in two complementary halves and addresses antigen combinations instead of single molecules. Each half, now coined hemibody, contains an antigen-specific single-chain variable fragment (scFv) fused to either the variable light (VL) or variable heavy (VH) chain domain of an anti-CD3 antibody. When the two hemibodies simultaneously bind their respective antigens on a single cell, they align and reconstitute the original CD3-binding site to engage T cells. Employing preclinical models for aggressive leukemia and breast cancer, we show that by the combinatorial nature of this approach, T lymphocytes exclusively eliminate dual antigen-positive cells while sparing single positive bystanders. This allows for precision targeting of cancers not amenable to current immunotherapies.
Molecular mechanism of a potassium channel gating through activation gate-selectivity filter coupling
Authors: Kopec Wojciech , Rothberg Brad S. , de Groot Bert L. 
Published: November 2019

AbstractPotassium channels are presumed to have two allosterically coupled gates, the activation gate and the selectivity filter gate, that control channel opening, closing, and inactivation. However, the molecular mechanism of how these gates regulate K+ ion flow through the channel remains poorly understood. An activation process, occurring at the selectivity filter, has been recently proposed for several potassium channels. Here, we use X-ray crystallography and extensive molecular dynamics simulations, to study ion permeation through a potassium channel MthK, for various opening levels of both gates. We find that the channel conductance is controlled at the selectivity filter, whose conformation depends on the activation gate. The crosstalk between the gates is mediated through a collective motion of channel helices, involving hydrophobic contacts between an isoleucine and a conserved threonine in the selectivity filter. We propose a gating model of selectivity filter-activated potassium channels, including pharmacologically relevant two-pore domain (K2P) and big potassium (BK) channels.
Structural insights into the formation and voltage degradation of lithium- and manganese-rich layered oxides
Authors: Hua Weibo , Wang Suning , Knapp Michael , Leake Steven J. , Senyshyn Anatoliy , Richter Carsten , Yavuz Murat , Binder Joachim R. , Grey Clare P. , Ehrenberg Helmut , Indris Sylvio , Schwarz Björn 
Published: November 2019

AbstractOne major challenge in the field of lithium-ion batteries is to understand the degradation mechanism of high-energy lithium- and manganese-rich layered cathode materials. Although they can deliver 30 % excess capacity compared with today’s commercially- used cathodes, the so-called voltage decay has been restricting their practical application. In order to unravel the nature of this phenomenon, we have investigated systematically the structural and compositional dependence of manganese-rich lithium insertion compounds on the lithium content provided during synthesis. Structural, electronic and electrochemical characterizations of LixNi0.2Mn0.6Oy with a wide range of lithium contents (0.00 ≤ x ≤ 1.52, 1.07 ≤ y < 2.4) and an analysis of the complexity in the synthesis pathways of monoclinic-layered Li[Li0.2Ni0.2Mn0.6]O2 oxide provide insight into the underlying processes that cause voltage fading in these cathode materials, i.e. transformation of the lithium-rich layered phase to a lithium-poor spinel phase via an intermediate lithium-containing rock-salt phase with release of lithium/oxygen.
Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network
Authors: Haupt Sue , Caramia Franco , Herschtal Alan , Soussi Thierry , Lozano Guillermina , Chen Hu , Liang Han , Speed Terence P. , Haupt Ygal 
Published: November 2019

AbstractThe disproportionately high prevalence of male cancer is poorly understood. We tested for sex-disparity in the functional integrity of the major tumor suppressor p53 in sporadic cancers. Our bioinformatics analyses expose three novel levels of p53 impact on sex-disparity in 12 non-reproductive cancer types. First, TP53 mutation is more frequent in these cancers among US males than females, with poorest survival correlating with its mutation. Second, numerous X-linked genes are associated with p53, including vital genomic regulators. Males are at unique risk from alterations of their single copies of these genes. High expression of X-linked negative regulators of p53 in wild-type TP53 cancers corresponds with reduced survival. Third, females exhibit an exceptional incidence of non-expressed mutations among p53-associated X-linked genes. Our data indicate that poor survival in males is contributed by high frequencies of TP53 mutations and an inability to shield against deregulated X-linked genes that engage in p53 networks.
Targeting mutant p53-expressing tumours with a T cell receptor-like antibody specific for a wild-type antigen
Authors: Low Lionel , Goh Angeline , Koh Joanna , Lim Samantha , Wang Cheng-I 
Published: November 2019

AbstractAccumulation of mutant p53 proteins is frequently found in a wide range of cancers. While conventional antibodies fail to target intracellular proteins, proteosomal degradation results in the presentation of p53-derived peptides on the tumour cell surface by class I molecules of the major histocompatibility complex (MHC). Elevated levels of such p53-derived peptide-MHCs on tumour cells potentially differentiate them from healthy tissues. Here, we report the engineering of an affinity-matured human antibody, P1C1TM, specific for the unmutated p53125-134peptide in complex with the HLA-A24 class I MHC molecule. We show that P1C1TM distinguishes between mutant and wild-type p53 expressing HLA-A24+cells, and mediates antibody dependent cellular cytotoxicity of mutant p53 expressing cells in vitro. Furthermore, we show that cytotoxic PNU-159682-P1C1TM drug conjugates specifically inhibit growth of mutant p53 expressing cells in vitro and in vivo. Hence, p53-associated peptide-MHCs are attractive targets for the immunotherapy against mutant p53 expressing tumours.
Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development
Authors: Seishima Ryo , Leung Carly , Yada Swathi , Murad Katzrin Bte Ahmed , Tan Liang Thing , Hajamohideen Amin , Tan Si Hui , Itoh Hideki , Murakami Kazuhiro , Ishida Yoshihiro , Nakamizo Satoshi , Yoshikawa Yusuke , Wong Esther , Barker Nick 
Published: November 2019

AbstractWnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential for the development of glandular epithelia in the intestine and stomach, but their existence in the developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models to identify Lgr5-expressing cells in the developing uterus and to evaluate their stem cell identity and function. Lgr5 is broadly expressed in the uterine epithelium during embryogenesis, but becomes largely restricted to the tips of developing glands after birth. In-vivo lineage tracing/ablation/organoid culture assays identify these gland-resident Lgr5high cells as Wnt-dependent stem cells responsible for uterine gland development. Adjacent Lgr5neg epithelial cells within the neonatal glands function as essential niche components to support the function of Lgr5high stem cells ex-vivo. These findings constitute a major advance in our understanding of uterine development and lay the foundations for investigating potential contributions of Lgr5+ stem/progenitor cells to uterine disorders.
Spatial variance of spring phenology in temperate deciduous forests is constrained by background climatic conditions
Authors: Peaucelle Marc , Janssens Ivan A. , Stocker Benjamin D. , Descals Ferrando Adrià , Fu Yongshuo H. , Molowny-Horas Roberto , Ciais Philippe , Peñuelas Josep 
Published: November 2019

AbstractLeaf unfolding in temperate forests is driven by spring temperature, but little is known about the spatial variance of that temperature dependency. Here we use in situ leaf unfolding observations for eight deciduous tree species to show that the two factors that control chilling (number of cold days) and heat requirement (growing degree days at leaf unfolding, GDDreq) only explain 30% of the spatial variance of leaf unfolding. Radiation and aridity differences among sites together explain 10% of the spatial variance of leaf unfolding date, and 40% of the variation in GDDreq. Radiation intensity is positively correlated with GDDreq and aridity is negatively correlated with GDDreq spatial variance. These results suggest that leaf unfolding of temperate deciduous trees is adapted to local mean climate, including water and light availability, through altered sensitivity to spring temperature. Such adaptation of heat requirement to background climate would imply that models using constant temperature response are inherently inaccurate at local scale.
Orbitally dominated Rashba-Edelstein effect in noncentrosymmetric antiferromagnets
Authors: Salemi Leandro , Berritta Marco , Nandy Ashis K. , Oppeneer Peter M. 
Published: November 2019

AbstractEfficient manipulation of magnetic order with electric current pulses is desirable for achieving fast spintronic devices. The Rashba-Edelstein effect, wherein spin polarization is electrically induced in noncentrosymmetric systems, provides a mean to achieve staggered spin-orbit torques. Initially predicted for spin, its orbital counterpart has been disregarded up to now. Here we report a generalized Rashba-Edelstein effect, which generates not only spin polarization but also orbital polarization, which we find to be far from being negligible. We show that the orbital Rashba-Edelstein effect does not require spin-orbit coupling to exist. We present first-principles calculations of the frequency-dependent spin and orbital Rashba-Edelstein tensors for the noncentrosymmetric antiferromagnets CuMnAs and Mn$${}_{2}$$2Au. We show that the electrically induced local magnetization can exhibit Rashba-like or Dresselhaus-like symmetries, depending on the magnetic configuration. We compute sizable induced magnetizations at optical frequencies, which suggest that electric-field driven switching could be achieved at much higher frequencies.
Multivariate chemometrics as a key tool for prediction of K and Fe in a diverse German agricultural soil-set using EDXRF
Authors: Büchele Dominique , Chao Madlen , Ostermann Markus , Leenen Matthias , Bald Ilko 
Published: November 2019

AbstractWithin the framework of precision agriculture, the determination of various soil properties is moving into focus, especially the demand for sensors suitable for in-situ measurements. Energy-dispersive X-ray fluorescence (EDXRF) can be a powerful tool for this purpose. In this study a huge diverse soil set (n = 598) from 12 different study sites in Germany was analysed with EDXRF. First, a principal component analysis (PCA) was performed to identify possible similarities among the sample set. Clustering was observed within the four texture classes clay, loam, silt and sand, as clay samples contain high and sandy soils low iron mass fractions. Furthermore, the potential of uni- and multivariate data evaluation with partial least squares regression (PLSR) was assessed for accurate determination of nutrients in German agricultural samples using two calibration sample sets. Potassium and iron were chosen for testing the performance of both models. Prediction of these nutrients in 598 German soil samples with EDXRF was more accurate using PLSR which is confirmed by a better overall averaged deviation and PLSR should therefore be preferred.
Watershed geomorphology modifies the sensitivity of aquatic ecosystem metabolism to temperature
Authors: Jankowski K. J. , Schindler D. E. 
Published: November 2019

AbstractThe regulation of aquatic carbon cycles by temperature is a significant uncertainty in our understanding of how watersheds will respond to climate change. Aquatic ecosystems transport substantial quantities of carbon to the atmosphere and ocean, yet we have limited understanding of how temperature modifies aquatic ecosystem metabolic processes and contributions to carbon cycles at watershed to global scales. We propose that geomorphology controls the distribution and quality of organic material that forms the metabolic base of aquatic ecosystems, thereby controlling the response of aquatic ecosystem metabolism to temperature across landscapes. Across 23 streams and four years during summer baseflow, we estimated variation in the temperature sensitivity of ecosystem respiration (R) among streams draining watersheds with different geomorphic characteristics across a boreal river basin. We found that geomorphic features imposed strong controls on temperature sensitivity; R in streams draining flat watersheds was up to six times more temperature sensitive than streams draining steeper watersheds. Further, our results show that this association between watershed geomorphology and temperature sensitivity of R was linked to the carbon quality of substrates that changed systematically across the geomorphic gradient. This suggests that geomorphology will control how carbon is transported, stored, and incorporated into river food webs as the climate warms.
A new method based on diffusive gradients in thin films for in situ monitoring microcystin-LR in waters
Authors: Yao Lei , Steinman Alan D. , Wan Xiang , Shu Xiubo , Xie Liqiang 
Published: November 2019

AbstractThe passive sampling method of diffusive gradients in thin-films (DGT) was developed to provide a quantitative and time-integrated measurement of microcystin-LR (MC-LR) in waters. The DGT method in this study used HLB (hydrophilic-lipophilic-balanced) material as a binding agent, and methanol as an eluent. The diffusion coefficient of MC-LR was 5.01 × 10−6 cm2 s−1 at 25 °C in 0.45 mm thick diffusion layer. This DGT method had a binding capacity of 4.24 μg per binding gel disk (3.14 cm2), ensuring sufficient capacity to measure MC-LR in most water matrices. The detection limit of HLB DGT was 0.48 ng L−1. DGT coupled to analysis by HPLC appears to be an accurate method for MC-LR monitoring. Comparison of DGT measurements for MC-LR in water and a conventional active sampling method showed little difference. This study demonstrates that HLB-based DGT is a useful tool for in situ monitoring of MC-LR in fresh waters.
First molecular detection of Toxoplasma gondii in vegetable samples in China using qualitative, quantitative real-time PCR and multilocus genotyping
Authors: Lass Anna , Ma Liqing , Kontogeorgos Ioannis , Zhang Xueyong , Li Xiuping , Karanis Panagiotis 
Published: November 2019

AbstractToxoplasma gondii infection is becoming increasing problem in China but there is no data concerning contamination of vegetables intended for consumption with this parasite. The aim of the present study was to investigate fresh vegetables originated from open markets located in the Xining City, the Qinghai-Tibet Plateau (QTP), P.R. China for their contamination with T. gondii. A total of 279 fresh vegetable samples were collected and analysed using real-time PCR assay targeting B1 gene and multilocus genotyping. T. gondii DNA was found in 10 (3.6%) samples tested; eight of them represented T. gondii type I and remaining two T. gondii type II. The approximate level of contamination of positive vegetables samples, estimated based on quantitative real-time PCR (qPCR), ranged between less than one and 27000 T. gondii oocysts per sample, with majority not exceeding several oocysts per sample. The results of the study confirmed that T. gondii is present in vegetables offered in open markets in the Qinghai province, P.R. China; eating them unwashed and raw may therefore pose a threat to consumers. This is the first investigation describing T. gondii detection in fresh vegetables intended for consumption collected from the territory of P.R. China using sensitive molecular tools.