bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ atomistic insight into the growth mechanisms of single layer 2D transition metal carbides
Authors: Sang Xiahan , Xie Yu , Yilmaz Dundar E. , Lotfi Roghayyeh , Alhabeb Mohamed , Ostadhossein Alireza , Anasori Babak , Sun Weiwei , Li Xufan , Xiao Kai , Kent Paul R. C. , van Duin Adri C. T. , Gogotsi Yury , Unocic Raymond R. 
Published: June 2018

AbstractDeveloping strategies for atomic-scale controlled synthesis of new two-dimensional (2D) functional materials will directly impact their applications. Here, using in situ aberration-corrected scanning transmission electron microscopy, we obtain direct insight into the homoepitaxial Frank–van der Merwe atomic layer growth mechanism of TiC single adlayers synthesized on surfaces of Ti3C2 MXene substrates with the substrate being the source material. Activated by thermal exposure and electron-beam irradiation, hexagonal TiC single adlayers form on defunctionalized surfaces of Ti3C2 MXene at temperatures above 500 °C, generating new 2D materials Ti4C3 and Ti5C4. The growth mechanism for a single TiC adlayer and the energies that govern atom migration and diffusion are elucidated by comprehensive density functional theory and force-bias Monte Carlo/molecular dynamics simulations. This work could lead to the development of bottom-up synthesis methods using substrates terminated with similar hexagonal-metal surfaces, for controllable synthesis of larger-scale and higher quality single-layer transition metal carbides.
Drivers of woody plant encroachment over Africa
Authors: Venter Z. S. , Cramer M. D. , Hawkins H.-J. 
Published: June 2018

AbstractWhile global deforestation induced by human land use has been quantified, the drivers and extent of simultaneous woody plant encroachment (WPE) into open areas are only regionally known. WPE has important consequences for ecosystem functioning, global carbon balances and human economies. Here we report, using high-resolution satellite imagery, that woody vegetation cover over sub-Saharan Africa increased by 8% over the past three decades and that a diversity of drivers, other than CO2, were able to explain 78% of the spatial variation in this trend. A decline in burned area along with warmer, wetter climates drove WPE, although this has been mitigated in areas with high population growth rates, and high and low extremes of herbivory, specifically browsers. These results confirm global greening trends, thereby bringing into question widely held theories about declining terrestrial carbon balances and desert expansion. Importantly, while global drivers such as climate and CO2 may enhance the risk of WPE, managing fire and herbivory at the local scale provides tools to mitigate continental WPE.
SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity
Authors: Yao Fan , Zhou Zhicheng , Kim Jongchan , Hang Qinglei , Xiao Zhenna , Ton Baochau N. , Chang Liang , Liu Na , Zeng Liyong , Wang Wenqi , Wang Yumeng , Zhang Peijing , Hu Xiaoyu , Su Xiaohua , Liang Han , Sun Yutong , Ma Li 
Published: June 2018

AbstractDysregulation of YAP localization and activity is associated with pathological conditions such as cancer. Although activation of the Hippo phosphorylation cascade is known to cause cytoplasmic retention and inactivation of YAP, emerging evidence suggests that YAP can be regulated in a Hippo-independent manner. Here, we report that YAP is subject to non-proteolytic, K63-linked polyubiquitination by the SCFSKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1. The non-proteolytic ubiquitination of YAP enhances its interaction with its nuclear binding partner TEAD, thereby inducing YAP’s nuclear localization, transcriptional activity, and growth-promoting function. Independently of Hippo signaling, mutation of YAP’s K63-linkage specific ubiquitination sites K321 and K497, depletion of SKP2, or overexpression of OTUD1 retains YAP in the cytoplasm and inhibits its activity. Conversely, overexpression of SKP2 or loss of OTUD1 leads to nuclear localization and activation of YAP. Altogether, our study sheds light on the ubiquitination-mediated, Hippo-independent regulation of YAP.
Map of synthetic rescue interactions for the Fanconi anemia DNA repair pathway identifies USP48
Authors: Velimezi Georgia , Robinson-Garcia Lydia , Muñoz-Martínez Francisco , Wiegant Wouter W. , Ferreira da Silva Joana , Owusu Michel , Moder Martin , Wiedner Marc , Rosenthal Sara Brin , Fisch Kathleen M. , Moffat Jason , Menche Jörg , van Attikum Haico , Jackson Stephen P. , Loizou Joanna I. 
Published: June 2018

AbstractDefects in DNA repair can cause various genetic diseases with severe pathological phenotypes. Fanconi anemia (FA) is a rare disease characterized by bone marrow failure, developmental abnormalities, and increased cancer risk that is caused by defective repair of DNA interstrand crosslinks (ICLs). Here, we identify the deubiquitylating enzyme USP48 as synthetic viable for FA-gene deficiencies by performing genome-wide loss-of-function screens across a panel of human haploid isogenic FA-defective cells (FANCA, FANCC, FANCG, FANCI, FANCD2). Thus, as compared to FA-defective cells alone, FA-deficient cells additionally lacking USP48 are less sensitive to genotoxic stress induced by ICL agents and display enhanced, BRCA1-dependent, clearance of DNA damage. Consequently, USP48 inactivation reduces chromosomal instability of FA-defective cells. Our results highlight a role for USP48 in controlling DNA repair and suggest it as a potential target that could be therapeutically exploited for FA.
Transport regimes of a split gate superconducting quantum point contact in the two-dimensional LaAlO3/SrTiO3 superfluid
Authors: Thierschmann Holger , Mulazimoglu Emre , Manca Nicola , Goswami Srijit , Klapwijk Teun M. , Caviglia Andrea D. 
Published: June 2018

AbstractOne of the hallmark experiments of quantum transport is the observation of the quantized resistance in a point contact in GaAs/AlGaAs heterostructures. Being formed with split gate technology, these structures represent in an ideal manner equilibrium reservoirs which are connected only through a few electron mode channel. It has been a long standing goal to achieve similar experimental conditions also in superconductors. Here we demonstrate the formation of a superconducting quantum point contact (SQPC) with split gate technology in a two-dimensional superconductor, utilizing the unique gate tunability of the superfluid at the LaAlO3/SrTiO3 interface. When the constriction is tuned through the action of metallic split gates we identify three regimes of transport: First, SQPC for which the supercurrent is carried only by a few quantum transport channels. Second, superconducting island strongly coupled to the equilibrium reservoirs. Third, charge island with a discrete spectrum weakly coupled to the reservoirs.
Postsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons
Authors: Wang Jiejie , Lv Xinyou , Wu Yu , Xu Tao , Jiao Mingfei , Yang Risheng , Li Xia , Chen Ming , Yan Yinggang , Chen Changwan , Dong Weifan , Yang Wei , Zhuo Min , Chen Tao , Luo Jianhong , Qiu Shuang 
Published: June 2018

AbstractNMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory. Moreover, RIM1 levels in hippocampal neurons influence both the constitutive and regulated NMDAR trafficking, without affecting constitutive AMPAR trafficking. We further demonstrate that RIM1 binds to Rab11 via its N terminus, and knockdown of RIM1 impairs membrane insertion of Rab11-positive recycling endosomes containing NMDARs. Together, these results identify a RIM1-dependent mechanism critical for modulating synaptic function by facilitating membrane delivery of recycling NMDARs.
Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity
Authors: Strunz Benedikt , Hengst Julia , Deterding Katja , Manns Michael P. , Cornberg Markus , Ljunggren Hans-Gustaf , Wedemeyer Heiner , Björkström Niklas K. 
Published: June 2018

AbstractDiversity is a central requirement for the immune system’s capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface
Authors: Tang Maggie K. S. , Yue Patrick Y. K. , Ip Philip P. , Huang Rui-Lan , Lai Hung-Cheng , Cheung Annie N. Y. , Tse Ka Yu , Ngan Hextan Y. S. , Wong Alice S. T. 
Published: June 2018

AbstractThe limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.
Diversity and evolution of the emerging Pandoraviridae family
Authors: Legendre Matthieu , Fabre Elisabeth , Poirot Olivier , Jeudy Sandra , Lartigue Audrey , Alempic Jean-Marie , Beucher Laure , Philippe Nadège , Bertaux Lionel , Christo-Foroux Eugène , Labadie Karine , Couté Yohann , Abergel Chantal , Claverie Jean-Michel 
Published: June 2018

AbstractWith DNA genomes reaching 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infecting pandoraviruses remained up to now the most complex viruses since their discovery in 2013. Our isolation of three new strains from distant locations and environments is now used to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses reveals many non-coding transcripts and significantly reduces the former set of predicted protein-coding genes. Here we show that the pandoraviruses exhibit an open pan-genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain-specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggest that de novo gene creation could contribute to the evolution of the giant pandoravirus genomes.
Nanoscale membranes that chemically isolate and electronically wire up the abiotic/biotic interface
Authors: Cornejo Jose A. , Sheng Hua , Edri Eran , M. Ajo-Franklin Caroline , Frei Heinz 
Published: June 2018

AbstractBy electrochemically coupling microbial and abiotic catalysts, bioelectrochemical systems such as microbial electrolysis cells and microbial electrosynthesis systems synthesize energy-rich chemicals from energy-poor precursors with unmatched efficiency. However, to circumvent chemical incompatibilities between the microbial cells and inorganic materials that result in toxicity, corrosion, fouling, and efficiency-degrading cross-reactions between oxidation and reduction environments, bioelectrochemical systems physically separate the microbial and inorganic catalysts by macroscopic distances, thus introducing ohmic losses, rendering these systems impractical at scale. Here we electrochemically couple an inorganic catalyst, a SnO2 anode, with a microbial catalyst, Shewanella oneidensis, via a 2-nm-thick silica membrane containing -CN and -NO2 functionalized p-oligo(phenylene vinylene) molecular wires. This membrane enables electron flow at 0.51 μA cm−2 from microbial catalysts to the inorganic anode, while blocking small molecule transport. Thus the modular architecture avoids chemical incompatibilities without ohmic losses and introduces an immense design space for scale up of bioelectrochemical systems.
Interplay of the two ancient metabolites auxin and MEcPP regulates adaptive growth
Authors: Jiang Jishan , Rodriguez-Furlan Cecilia , Wang Jin-Zheng , de Souza Amancio , Ke Haiyan , Pasternak Taras , Lasok Hanna , Ditengou Franck A. , Palme Klaus , Dehesh Katayoon 
Published: June 2018

AbstractThe ancient morphoregulatory hormone auxin dynamically realigns dedicated cellular processes that shape plant growth under prevailing environmental conditions. However, the nature of the stress-responsive signal altering auxin homeostasis remains elusive. Here we establish that the evolutionarily conserved plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) controls adaptive growth by dual transcriptional and post-translational regulatory inputs that modulate auxin levels and distribution patterns in response to stress. We demonstrate that in vivo accumulation or exogenous application of MEcPP alters the expression of two auxin reporters, DR5:GFP and DII-VENUS, and reduces the abundance of the auxin-efflux carrier PIN-FORMED1 (PIN1) at the plasma membrane. However, pharmacological intervention with clathrin-mediated endocytosis blocks the PIN1 reduction. This study provides insight into the interplay between these two indispensable signaling metabolites by establishing the mode of MEcPP action in altering auxin homeostasis, and as such, positioning plastidial function as the primary driver of adaptive growth.
Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment
Authors: Scheggia Diego , Mastrogiacomo Rosa , Mereu Maddalena , Sannino Sara , Straub Richard E. , Armando Marco , Managò Francesca , Guadagna Simone , Piras Fabrizio , Zhang Fengyu , Kleinman Joel E. , Hyde Thomas M. , Kaalund Sanne S. , Pontillo Maria , Orso Genny , Caltagirone Carlo , Borrelli Emiliana , De Luca Maria A. , Vicari Stefano , Weinberger Daniel R. , Spalletta Gianfranco , Papaleo Francesco 
Published: June 2018

AbstractAntipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.
Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation
Authors: Zheng Dinghai , Wang Ruijia , Ding Qingbao , Wang Tianying , Xie Bingning , Wei Lu , Zhong Zhaohua , Tian Bin 
Published: June 2018

AbstractMost eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3′UTR lengths, production of which is influenced by cellular conditions. Here, we show that arsenic stress elicits global shortening of 3′UTRs through preferential usage of proximal polyadenylation sites during stress and enhanced degradation of long 3′UTR isoforms during recovery. We demonstrate that RNA-binding protein TIA1 preferentially interacts with alternative 3′UTR sequences through U-rich motifs, correlating with stress granule association and mRNA decay of long 3′UTR isoforms. By contrast, genes with shortened 3′UTRs due to stress-induced APA can evade mRNA clearance and maintain transcript abundance post stress. Furthermore, we show that stress causes distinct 3′UTR size changes in proliferating and differentiated cells, highlighting its context-specific impacts on the 3′UTR landscape. Together, our data reveal a global, 3′UTR-based mRNA stability control in stressed cells and indicate that APA can function as an adaptive mechanism to preserve mRNAs in response to stress.
An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex
Authors: Kawauchi Keiko , Sugimoto Wataru , Yasui Takatoshi , Murata Kohei , Itoh Katsuhiko , Takagi Kazuki , Tsuruoka Takaaki , Akamatsu Kensuke , Tateishi-Karimata Hisae , Sugimoto Naoki , Miyoshi Daisuke 
Published: June 2018

AbstractAberrant activation of RAS signalling pathways contributes to aggressive phenotypes of cancer cells. The RAS-targeted therapies for cancer, therefore, have been recognised to be effective; however, current developments on targeting RAS have not advanced due to structural features of the RAS protein. Here, we show that expression of NRAS, a major isoform of RAS, can be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA. In vitro experiments reveal that ZnAPC binds to a G-quadruplex–forming oligonucleotide derived from the 5′-untranslated region of NRAS mRNA even in the presence of excess double-stranded RNA, which is abundant in cells, resulting in selective cleavage of the target RNA’s G-quadruplex upon photo-irradiation. In line with these results, upon photo-irradiation, ZnAPC decreases NRAS mRNA and NRAS expression and thus viability of cancer cells. These results indicate that ZnAPC may be a prominent photosensitiser for a molecularly targeted photodynamic therapy for cancer.
Mapping biological process relationships and disease perturbations within a pathway network
Authors: Stoney Ruth , Robertson David L , Nenadic Goran , Schwartz Jean-Marc 
Published: June 2018

AbstractMolecular interaction networks are routinely used to map the organization of cellular function. Edges represent interactions between genes, proteins, or metabolites. However, in living cells, molecular interactions are dynamic, necessitating context-dependent models. Contextual information can be integrated into molecular interaction networks through the inclusion of additional molecular data, but there are concerns about completeness and relevance of this data. We developed an approach for representing the organization of human cellular processes using pathways as the nodes in a network. Pathways represent spatial and temporal sets of context-dependent interactions, generating a high-level network when linked together, which incorporates contextual information without the need for molecular interaction data. Analysis of the pathway network revealed linked communities representing functional relationships, comparable to those found in molecular networks, including metabolism, signaling, immunity, and the cell cycle. We mapped a range of diseases onto this network and find that pathways associated with diseases tend to be functionally connected, highlighting the perturbed functions that result in disease phenotypes. We demonstrated that disease pathways cluster within the network. We then examined the distribution of cancer pathways and showed that cancer pathways tend to localize within the signaling, DNA processes and immune modules, although some cancer-associated nodes are found in other network regions. Altogether, we generated a high-confidence functional network, which avoids some of the shortcomings faced by conventional molecular models. Our representation provides an intuitive functional interpretation of cellular organization, which relies only on high-quality pathway and Gene Ontology data. The network is available athttps://data.mendeley.com/datasets/3pbwkxjxg9/1.
Expression of Cry2Aa, a Bacillus thuringiensis insecticidal protein in transgenic pigeon pea confers resistance to gram pod borer, Helicoverpa armigera
Authors: Singh Shweta , Kumar Nikhil Ram , Maniraj R. , Lakshmikanth R. , Rao K. Y. S. , Muralimohan N. , Arulprakash T. , Karthik K. , Shashibhushan N. B. , Vinutha T. , Pattanayak Debasis , Dash Prasanta K. , Kumar P. Ananda , Sreevathsa Rohini 
Published: June 2018

AbstractPigeon pea is an important legume infested by a plethora of insect pests amongst which gram pod borer Helicoverpa armigera is very prominent. Imparting resistance to this insect herbivore is of global importance in attaining food security. Expression of insecticidal crystal proteins (ICP) in diverse crops has led to increased resistance to several pests. We report in this paper, expression of Cry2Aa in transgenic pigeon pea and its effectiveness towards H. armigera by employing Agrobacterium-mediated in planta transformation approach. Approximately 0.8% of T1 generation plants were identified as putative transformants based on screening in the presence of 70 ppm kanamycin as the selection agent. Promising events were further recognized in advanced generations based on integration, expression and bioefficacy of the transgenes. Seven T3 lines (11.8% of the selected T1 events) were categorized as superior as these events demonstrated 80–100% mortality of the challenged larvae and improved ability to prevent damage caused by the larvae. The selected transgenic plants accumulated Cry2Aa in the range of 25–80 µg/g FW. The transgenic events developed in the study can be used in pigeon pea improvement programmes for pod borer resistance.