bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant Growth‐Promoting Rhizobacteria (PGPR) Reduce Evaporation and Increase Soil Water Retention
Authors: Zheng Wenjuan , Zeng Saiqi , Bais Harsh , LaManna Jacob M. , Hussey Daniel S. , Jacobson David L. , Jin Yan 
Published: April 2018

AbstractEnhancement of plant drought stress tolerance by plant growth‐promoting rhizobacteria (PGPR) has been increasingly documented in the literature. However, most studies to date have focused on PGPR‐root/plant interactions; very little is known about PGPR's role in mediating physiochemical and hydrological changes in the rhizospheric soil that may impact plant drought stress tolerance. Our study aimed to advance mechanistic understanding of PGPR‐mediated biophysical changes in the rhizospheric soil that may contribute to plant drought stress tolerance in addition to plant responses. We measured soil water retention characteristics, hydraulic conductivity, and water evaporation in soils with various textures (i.e., pure sand, sandy soil, and clay) as influenced by a representative PGPR (Bacillus subtilis strain UD1022) using the HYPROP system. We found that all PGPR‐treated soils held more water and had reduced hydraulic conductivity and accumulative evaporation, compared to their corresponding controls. We discuss three mechanisms, due to B. subtilis incubation or production of extracellular polymeric substances (EPS), that are potentially responsible for the changes in hydraulic properties and soil evaporation: (i) EPS have a large water holding capacity; (ii) EPS alter soil matrix structure and connectivity of pore space; (iii) EPS modify the physicochemical properties of water (surface tension and viscosity). These results clearly demonstrate PGPR's ability to increase water availability to plants by slowing down evaporation and by increasing the time available for plants to make metabolic adjustments to drought stress.
Donor-dependent variation of human umbilical cord blood mesenchymal stem cells in response to hypoxic preconditioning and amelioration of limb ischemia
Authors: Kang Insung , Lee Byung-Chul , Choi Soon Won , Lee Jin Young , Kim Jae-Jun , Kim Bo-Eun , Kim Da-Hyun , Lee Seung Eun , Shin Nari , Seo Yoojin , Kim Hyung-Sik , Kim Dong-Ik , Kang Kyung-Sun 
Published: April 2018

AbstractWith the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Because of their immunosuppressive properties, MSCs are commonly used as an allogeneic treatment. However, for the many donors who could potentially be used, it is important to understand the capacity for therapeutic usage with donor-to-donor heterogeneity. In this study, we aimed to investigate MSCs as a promising therapeutic strategy for critical limb ischemia. We evaluated MSCs from two donors (#55 and #64) and analyzed the capacity for angiogenesis through in vivo and in vitro assays to compare the therapeutic effect between different donors. We emphasized the importance of intra-population heterogeneity of MSCs on therapeutic usage by evaluating the effects of hypoxia on activating cellular angiogenesis in MSCs. The precondition of hypoxia in MSCs is known to enhance therapeutic efficacy. Our study suggests that sensitivity to hypoxic conditions is different between cells originating from different donors, and this difference affects the contribution to angiogenesis. The bioinformatics analysis of different donors under hypoxic culture conditions identified intrinsic variability in gene expression patterns and suggests alternative potential genetic factors ANGPTL4, ADM, SLC2A3, and CDON as guaranteed general indicators for further stem cell therapy.
Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models
Authors: Syn Nicholas L. , Lim Pei Li , Kong Li Ren , Wang Lingzhi , Wong Andrea Li-Ann , Lim Chwee Ming , Loh Thomas Kwok Seng , Siemeister Gerhard , Goh Boon Cher , Hsieh Wen-Son 
Published: April 2018

AbstractIn addition to their canonical roles in regulating cell cycle transition and transcription, cyclin-dependent kinases (CDKs) have been shown to coordinate DNA damage response pathways, suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies. Here, we report that roniciclib (BAY1000394), a potent pan-CDK inhibitor, displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma (NPC) models. Proliferation of the NPC cell lines HONE-1, CNE-2, C666-1, and HK-1 was effectively curbed by roniciclib treatment, with IC50 values between 11 and 38 nmol/L. These anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1, 2, 3, and 4 and transcriptional CDKs 7 and 9, ultimately resulting in arrest at G1/S and G2/M, downregulation of the transcriptional apparatus, and repression of anti-apoptotic proteins. Considerably enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0 μmol/L cisplatin; this combination therapy achieved a response over 250% greater than either drug alone. Although roniciclib chemosensitized NPC cells to cisplatin, it did not sensitize untransformed (NP69) cells. The administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin, whereas combining these two agents produced far greater tumor suppression than either of the monotherapies. In summary, these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses, thus justifying further evaluation of this combinatorial approach in clinical settings.
THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders
Authors: Guennewig Boris , Bitar Maina , Obiorah Ifeanyi , Hanks James , O’Brien Elizabeth A. , Kaczorowski Dominik C. , Hurd Yasmin L. , Roussos Panos , Brennand Kristen J. , Barry Guy 
Published: April 2018

AbstractThere is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Δ9-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC.
Increased functional connectivity of the posterior cingulate cortex with the lateral orbitofrontal cortex in depression
Authors: Cheng Wei , Rolls Edmund T. , Qiu Jiang , Xie Xiongfei , Wei Dongtao , Huang Chu-Chung , Yang Albert C. , Tsai Shih-Jen , Li Qi , Meng Jie , Lin Ching-Po , Xie Peng , Feng Jianfeng 
Published: April 2018

AbstractTo analyze the functioning of the posterior cingulate cortex (PCC) in depression, we performed the first fully voxel-level resting state functional-connectivity neuroimaging analysis of depression of the PCC, with 336 patients with major depressive disorder and 350 controls. Voxels in the PCC had significantly increased functional connectivity with the lateral orbitofrontal cortex, a region implicated in non-reward and which is thereby implicated in depression. In patients receiving medication, the functional connectivity between the lateral orbitofrontal cortex and PCC was decreased back towards that in the controls. In the 350 controls, it was shown that the PCC has high functional connectivity with the parahippocampal regions which are involved in memory. The findings support the theory that the non-reward system in the lateral orbitofrontal cortex has increased effects on memory systems, which contribute to the rumination about sad memories and events in depression. These new findings provide evidence that a key target to ameliorate depression is the lateral orbitofrontal cortex.
Exosomal circRNA_100284 from arsenite-transformed cells, via microRNA-217 regulation of EZH2, is involved in the malignant transformation of human hepatic cells by accelerating the cell cycle and promoting cell proliferation
Authors: Dai Xiangyu , Chen Chao , Yang Qianlei , Xue Junchao , Chen Xiong , Sun Baofei , Luo Fei , Liu Xinlu , Xiao Tian , Xu Hui , Sun Qian , Zhang Aihua , Liu Qizhan 
Published: April 2018

AbstractIntercellular communication between malignant cells and neighboring nonmalignant cells is involved in carcinogenesis. In the progression of carcinogenesis, exosomes are messengers for intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs with functions that include regulation of the cell cycle and proliferation. However, the functions of exosomal circRNAs are not clear. The present research aimed to determine whether circRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 cells and become functionally active in the normal cells. The results showed that circRNA_100284 is involved in the malignant transformation of L-02 cells induced by arsenite. The medium from transformed L-02 cells induced upregulation of circRNA_100284, accelerated the cell cycle, and promoted proliferation of normal L-02 cells. Transformed cells transferred circRNA_100284 into normal L-02 cells via exosomes and led to the malignant transformation of the non-transformed cells. Knockdown of circRNA_100284, which reduced circRNA_100284 levels in exosomes derived from transformed L-02 cells, blocked the accelerated cell cycle and reduced proliferation and malignancy. In addition, in normal L-02 cells, exosomal circRNA_100284 derived from arsenite-transformed L-02 cells induced acceleration of the cell cycle and promoted proliferation via acting as a sponge of microRNA-217. Further, exosomal circRNA_100284 was upregulated in the sera of people exposed to arsenite. Thus, exosomes derived from transformed L-02 cells transferred circRNA_100284 to surrounding cells, which induced an accelerated cell cycle and promoted proliferation of normal liver cells and led to the malignant transformation of the non-transformed cells. The findings support the concept that exosomal circRNAs are involved in cell–cell communication during carcinogenesis induced by arsenite.
Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies
Authors: Boyd Mette , Thodberg Malte , Vitezic Morana , Bornholdt Jette , Vitting-Seerup Kristoffer , Chen Yun , Coskun Mehmet , Li Yuan , Lo Bobby Zhao Sheng , Klausen Pia , Jan Schweiger Pawel , Pedersen Anders Gorm , Rapin Nicolas , Skovgaard Kerstin , Dahlgaard Katja , Andersson Robin , Terkelsen Thilde Bagger , Lilje Berit , Troelsen Jesper Thorvald , Petersen Andreas Munk , Jensen Kim Bak , Gögenur Ismail , Thielsen Peter , Seidelin Jakob Benedict , Nielsen Ole Haagen , Bjerrum Jacob Tveiten , Sandelin Albin 
Published: April 2018

AbstractInflammatory bowel disease (IBD) is a chronic intestinal disorder, with two main types: Crohn’s disease (CD) and ulcerative colitis (UC), whose molecular pathology is not well understood. The majority of IBD-associated SNPs are located in non-coding regions and are hard to characterize since regulatory regions in IBD are not known. Here we profile transcription start sites (TSSs) and enhancers in the descending colon of 94 IBD patients and controls. IBD-upregulated promoters and enhancers are highly enriched for IBD-associated SNPs and are bound by the same transcription factors. IBD-specific TSSs are associated to genes with roles in both inflammatory cascades and gut epithelia while TSSs distinguishing UC and CD are associated to gut epithelia functions. We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.
Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus
Authors: Abdi Khadar , Lai Chun-Hsiang , Paez-Gonzalez Patricia , Lay Mark , Pyun Joon , Kuo Chay T. 
Published: April 2018

AbstractSpecialized, differentiated cells often perform unique tasks that require them to maintain a stable phenotype. Multiciliated ependymal cells (ECs) are unique glial cells lining the brain ventricles, important for cerebral spinal fluid circulation. While functional ECs are needed to prevent hydrocephalus, they have also been reported to generate new neurons: whether ECs represent a stable cellular population remains unclear. Via a chemical screen we found that mature ECs are inherently plastic, with their multiciliated state needing constant maintenance by the Foxj1 transcription factor, which paradoxically is rapidly turned over by the ubiquitin-proteasome system leading to cellular de-differentiation. Mechanistic analyses revealed a novel NF-κB-independent IKK2 activity stabilizing Foxj1 in mature ECs, and we found that known IKK2 inhibitors including viruses and growth factors robustly induced Foxj1 degradation, EC de-differentiation, and hydrocephalus. Although mature ECs upon de-differentiation can divide and regenerate multiciliated ECs, we did not detect evidence supporting EC’s neurogenic potential.
Gold-catalyzed stereoselective cycloisomerization of allenoic acids for two types of common natural γ-butyrolactones
Authors: Zhou Jing , Fu Chunling , Ma Shengming 
Published: April 2018

Abstractγ-(E)-Vinylic and γ-alkylic γ-butyrolactones are two different types of lactones existing extensively in animals and plants and many of them show interesting biological activities. Nature makes alkylic γ-butyrolactones by many different enzymatic lactonization processes. Scientists have been mimicking the natural strategy by developing new catalysts. However, direct and efficient access to γ-(E)-vinylic γ-butyrolactones is still extremely limited. Here, we wish to present our modular allene approach, which provides an efficient asymmetric approach to (E)-vinylic γ-butyrolactones from allenoic acids by identifying a new gold complex as the catalyst. Based on this cycloisomerization strategy, the first syntheses of racemic xestospongiene and xestospongienes E, F, G, and H have been realized and the absolute configurations of the chiral centers in xestospongienes E and F have been revised. In addition, by applying a C–O bond cleavage-free hydrogenation, the syntheses of naturally occurring γ-alkylic γ-lactones, (R)-4-tetradecalactone, (S)-4-tetradecalactone, (R)-γ-palmitolactone, and (R)-4-decalactone, have also been achieved.
Correlation of the Dzyaloshinskii–Moriya interaction with Heisenberg exchange and orbital asphericity
Authors: Kim Sanghoon , Ueda Kohei , Go Gyungchoon , Jang Peong-Hwa , Lee Kyung-Jin , Belabbes Abderrezak , Manchon Aurelien , Suzuki Motohiro , Kotani Yoshinori , Nakamura Tetsuya , Nakamura Kohji , Koyama Tomohiro , Chiba Daichi , Yamada Kihiro. T. , Kim Duck-Ho , Moriyama Takahiro , Kim Kab-Jin , Ono Teruo 
Published: April 2018

AbstractChiral spin textures of a ferromagnetic layer in contact to a heavy non-magnetic metal, such as Néel-type domain walls and skyrmions, have been studied intensively because of their potential for future nanomagnetic devices. The Dyzaloshinskii–Moriya interaction (DMI) is an essential phenomenon for the formation of such chiral spin textures. In spite of recent theoretical progress aiming at understanding the microscopic origin of the DMI, an experimental investigation unravelling the physics at stake is still required. Here we experimentally demonstrate the close correlation of the DMI with the anisotropy of the orbital magnetic moment and with the magnetic dipole moment of the ferromagnetic metal in addition to Heisenberg exchange. The density functional theory and the tight-binding model calculations reveal that inversion symmetry breaking with spin–orbit coupling gives rise to the orbital-related correlation. Our study provides the experimental connection between the orbital physics and the spin–orbit-related phenomena, such as DMI.
Blackbody radiation shift assessment for a lutetium ion clock
Authors: Arnold K. J. , Kaewuam R. , Roy A. , Tan T. R. , Barrett M. D. 
Published: April 2018

AbstractThe accuracy of state-of-the-art atomic clocks is derived from the insensitivity of narrow optical atomic resonances to environmental perturbations. Two such resonances in singly ionized lutetium have been identified with potentially lower sensitivities compared to other clock candidates. Here we report measurement of the most significant unknown atomic property of both transitions, the static differential scalar polarizability. From this, the fractional blackbody radiation shift for one of the transitions is found to be −1.36(9) × 10−18 at 300 K, the lowest of any established optical atomic clock. In consideration of leading systematic effects common to all ion clocks, both transitions compare favorably to the most accurate ion-based clocks reported to date. This work firmly establishes Lu+ as a promising candidate for a future generation of more accurate optical atomic clocks.
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
Authors: Ali Mina , Ajore Ram , Wihlborg Anna-Karin , Niroula Abhishek , Swaminathan Bhairavi , Johnsson Ellinor , Stephens Owen W , Morgan Gareth , Meissner Tobias , Turesson Ingemar , Goldschmidt Hartmut , Mellqvist Ulf-Henrik , Gullberg Urban , Hansson Markus , Hemminki Kari , Nahi Hareth , Waage Anders , Weinhold Niels , Nilsson Björn 
Published: April 2018

AbstractRecently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
Magnetically tunable bidirectional locomotion of a self-assembled nanorod-sphere propeller
Authors: García-Torres José , Calero Carles , Sagués Francesc , Pagonabarraga Ignacio , Tierno Pietro 
Published: April 2018

AbstractField-driven direct assembly of nanoscale matter has impact in disparate fields of science. In microscale systems, such concept has been recently exploited to optimize propulsion in viscous fluids. Despite the great potential offered by miniaturization, using self-assembly to achieve transport at the nanoscale remains an elusive task. Here we show that a hybrid propeller, composed by a ferromagnetic nanorod and a paramagnetic microsphere, can be steered in a fluid in a variety of modes, from pusher to puller, when the pair is dynamically actuated by a simple oscillating magnetic field. We exploit this unique design to build more complex structures capable of carrying several colloidal cargos as microscopic trains that quickly disassemble at will under magnetic command. In addition, our prototype can be extended to smaller nanorods below the diffraction limit, but still dynamically reconfigurable by the applied magnetic field.
Stochastic system identification without an a priori chosen kinetic model—exploring feasible cell regulation with piecewise linear functions
Authors: Hoffmann Martin , Galle Jörg 
Published: April 2018

AbstractKinetic models are at the heart of system identification. A priori chosen rate functions may, however, be unfitting or too restrictive for complex or previously unanticipated regulation. We applied general purpose piecewise linear functions for stochastic system identification in one dimension using published flow cytometry data on E.coli and report on identification results for equilibrium state and dynamic time series. In metabolic labelling experiments during yeast osmotic stress response, we find mRNA production and degradation to be strongly co-regulated. In addition, mRNA degradation appears overall uncorrelated with mRNA level. Comparison of different system identification approaches using semi-empirical synthetic data revealed the superiority of single-cell tracking for parameter identification. Generally, we find that even within restrictive error bounds for deviation from experimental data, the number of viable regulation types may be large. Indeed, distinct regulation can lead to similar expression behaviour over time. Our results demonstrate that molecule production and degradation rates may often differ from classical constant, linear or Michaelis–Menten type kinetics.
Integrative annotation and knowledge discovery of kinase post-translational modifications and cancer-associated mutations through federated protein ontologies and resources
Authors: Huang Liang-Chin , Ross Karen E. , Baffi Timothy R. , Drabkin Harold , Kochut Krzysztof J. , Ruan Zheng , D’Eustachio Peter , McSkimming Daniel , Arighi Cecilia , Chen Chuming , Natale Darren A. , Smith Cynthia , Gaudet Pascale , Newton Alexandra C. , Wu Cathy , Kannan Natarajan 
Published: April 2018

AbstractMany bioinformatics resources with unique perspectives on the protein landscape are currently available. However, generating new knowledge from these resources requires interoperable workflows that support cross-resource queries. In this study, we employ federated queries linking information from the Protein Kinase Ontology, iPTMnet, Protein Ontology, neXtProt, and the Mouse Genome Informatics to identify key knowledge gaps in the functional coverage of the human kinome and prioritize understudied kinases, cancer variants and post-translational modifications (PTMs) for functional studies. We identify 32 functional domains enriched in cancer variants and PTMs and generate mechanistic hypotheses on overlapping variant and PTM sites by aggregating information at the residue, protein, pathway and species level from these resources. We experimentally test the hypothesis that S768 phosphorylation in the C-helix of EGFR is inhibitory by showing that oncogenic variants altering S768 phosphorylation increase basal EGFR activity. In contrast, oncogenic variants altering conserved phosphorylation sites in the ‘hydrophobic motif’ of PKCβII (S660F and S660C) are loss-of-function in that they reduce kinase activity and enhance membrane translocation. Our studies provide a framework for integrative, consistent, and reproducible annotation of the cancer kinomes.