bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIWIL2 suppresses Siah2-mediated degradation of HDAC3 and facilitates CK2α-mediated HDAC3 phosphorylation
Authors: Zhang Yingying , Zheng Xulei , Tan Hao , Lu Yilu , Tao Dachang , Liu Yunqiang , Ma Yongxin 
Published: April 2018

AbstractHDAC3 is involved in deacetylation of histone and non-histone proteins, having a key role in the regulation of gene transcription and also in the process of tumorgenesis. However, how HDAC3 is regulated in cancer remains largely unclear. Here, we showed that PIWIL2 can interact with HDAC3, leading to stabilization of HDAC3 from ubiquitin-mediated degradation by competitive association with E3 ubiquitin ligase Siah2. Furthermore, we found that expression of PIWIL2 enhanced HDAC3 activity via CK2α. PIWIL2 facilitated the interaction between HDAC3 and CK2α, thus exhibiting a promotion on the HDAC3 phosphorylation by CK2α. Further work showed that PIWIL2 could promote cell proliferation and suppress cell apoptosis via regulating HDAC3. Our present study firstly revealed that PIWIL2 can play a role in HDAC3-mediated epigenetic regulation on cancer cell proliferation and apoptosis. These findings provide a novel insight into the roles of PIWIL2 in tumorigenesis.
Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma
Authors: Zhao Yuanyuan , Yi Jun , Tao Leilei , Huang Guichun , Chu Xiaoyuan , Song Haizhu , Chen Longbang 
Published: April 2018

AbstractAlthough many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cells and was further activated upon ionizing radiation (IR) exposure. In addition, radioresistant cells acquired epithelial-to-mesenchymal transition (EMT) properties and stem quality. Wnt signaling was then found to be involved in radioresistance by promoting DNA damage repair. In our present study, high-mobility group box 1 protein (HMGB1), a chromatin-associated protein, was firstly found to be transactivated by Wnt signaling and mediate Wnt-induced radioresistance. The role of HMGB1 in the regulation of DNA damage repair with the activation of DNA damage checkpoint response in response to IR was the main cause of HMGB1-induced radioresistance.
Methamphetamine alters T cell cycle entry and progression: role in immune dysfunction
Authors: Potula Raghava , Haldar Bijayesh , Cenna Jonathan M , Sriram Uma , Fan Shongshan 
Published: April 2018

AbstractWe and others have demonstrated that stimulants such as methamphetamine (METH) exerts immunosuppressive effects on the host’s innate and adaptive immune systems and has profound immunological implications. Evaluation of the mechanisms responsible for T-cell immune dysregulation may lead to ways of regulating immune homeostasis during stimulant use. Here we evaluated the effects of METH on T cell cycle entry and progression following activation. Kinetic analyses of cell cycle progression of T-cell subsets exposed to METH demonstrated protracted G1/S phase transition and differentially regulated genes responsible for cell cycle regulation. This result was supported by in vivo studies where mice exposed to METH had altered G1 cell cycle phase and impaired T-cell proliferation. In addition, T cells subsets exposed to METH had significant decreased expression of cyclin E, CDK2 and transcription factor E2F1 expression. Overall, our results indicate that METH exposure results in altered T cell cycle entry and progression. Our findings suggest that disruption of cell cycle machinery due to METH may limit T-cell proliferation essential for mounting an effective adaptive immune response and thus may strongly contribute to deleterious effect on immune system.
Single rhodium atoms anchored in micropores for efficient transformation of methane under mild conditions
Authors: Tang Yu , Li Yuting , Fung Victor , Jiang De-en , Huang Weixin , Zhang Shiran , Iwasawa Yasuhiro , Sakata Tomohiro , Nguyen Luan , Zhang Xiaoyan , Frenkel Anatoly I. , Tao Franklin 
Published: April 2018

AbstractCatalytic transformation of CH4 under a mild condition is significant for efficient utilization of shale gas under the circumstance of switching raw materials of chemical industries to shale gas. Here, we report the transformation of CH4 to acetic acid and methanol through coupling of CH4, CO and O2 on single-site Rh1O5 anchored in microporous aluminosilicates in solution at ≤150 °C. The activity of these singly dispersed precious metal sites for production of organic oxygenates can reach about 0.10 acetic acid molecules on a Rh1O5 site per second at 150 °C with a selectivity of ~70% for production of acetic acid. It is higher than the activity of free Rh cations by >1000 times. Computational studies suggest that the first C–H bond of CH4 is activated by Rh1O5 anchored on the wall of micropores of ZSM-5; the formed CH3 then couples with CO and OH, to produce acetic acid over a low activation barrier.
Ruthenium(II)-enabled para-selective C–H difluoromethylation of anilides and their derivatives
Authors: Yuan Chunchen , Zhu Lei , Chen Changpeng , Chen Xiaolan , Yang Yong , Lan Yu , Zhao Yingsheng 
Published: April 2018

AbstractTransition-metal-catalyzed direct site-selective functionalization of arene C–H bonds has emerged as an innovative approach for building the core structure of pharmaceutical agents and other versatile complex compounds. However, para-selective C–H functionalization has seldom been explored, only a few examples, such as steric-hindered arenes, electron-rich arenes, and substrates with a directing group, have been reported to date. Here we describe the development of a ruthenium-enabled para-selective C–H difluoromethylation of anilides, indolines, and tetrahydroquinolines. This reaction tolerates various substituted arenes, affording para-difluoromethylation products in moderate to good yields. Results of a preliminary study of the mechanism indicate that chelation-assisted cycloruthenation might play a role in the selective activation of para-CAr–H bonds. Furthermore, this method provides a direct approach for the synthesis of fluorinated drug derivatives, which has important application for drug discovery and development.
RING tetramerization is required for nuclear body biogenesis and PML sumoylation
Authors: Wang Pengran , Benhenda Shirine , Wu Haiyan , Lallemand-Breitenbach Valérie , Zhen Tao , Jollivet Florence , Peres Laurent , Li Yuwen , Chen Sai-Juan , Chen Zhu , de Thé Hugues , Meng Guoyu 
Published: April 2018

AbstractProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray crystallography and SAXS characterization, we demonstrate that PML RING tetramerizes through highly conserved PML-specific sequences, which are required for NB assembly and PML sumoylation. Conserved residues implicated in RING dimerization of other TRIMs also contribute to PML tetramer stability. Wild-type PML rescues the ability of some RING mutants to form NBs as well as their sumoylation. Impaired RING tetramerization abolishes PML/RARA-driven leukemogenesis in vivo and arsenic-induced differentiation ex vivo. Our studies thus identify RING tetramerization as a key step in the NB macro-molecular scaffolding. They suggest that higher order RING interactions allow efficient UBC9 recruitment and thus change the biochemical nature of TRIM-facilitated post-translational modifications.
Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects
Authors: Corbet Cyril , Bastien Estelle , Draoui Nihed , Doix Bastien , Mignion Lionel , Jordan Bénédicte F. , Marchand Arnaud , Vanherck Jean-Christophe , Chaltin Patrick , Schakman Olivier , Becker Holger M. , Riant Olivier , Feron Olivier 
Published: April 2018

AbstractLactate exchange between glycolytic and oxidative cancer cells is proposed to optimize tumor growth. Blocking lactate uptake through monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic strategy but may stimulate glucose consumption by oxidative cancer cells. We report here that inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks of blocking lactate use while preventing glucose oxidative metabolism. Using in vitro 13C-glucose and in vivo hyperpolarized 13C-pyruvate, we identify 7ACC2 as a potent inhibitor of mitochondrial pyruvate transport which consecutively blocks extracellular lactate uptake by promoting intracellular pyruvate accumulation. Also, while in spheroids MCT1 inhibition leads to cytostatic effects, MPC activity inhibition induces cytotoxic effects together with glycolysis stimulation and uncompensated inhibition of mitochondrial respiration. Hypoxia reduction obtained with 7ACC2 is further shown to sensitize tumor xenografts to radiotherapy. This study positions MPC as a control point for lactate metabolism and expands on the anticancer potential of MPC inhibition.
Ecological control of nitrite in the upper ocean
Authors: Zakem Emily J. , Al-Haj Alia , Church Matthew J. , van Dijken Gert L. , Dutkiewicz Stephanie , Foster Sarah Q. , Fulweiler Robinson W. , Mills Matthew M. , Follows Michael J. 
Published: April 2018

AbstractMicroorganisms oxidize organic nitrogen to nitrate in a series of steps. Nitrite, an intermediate product, accumulates at the base of the sunlit layer in the subtropical ocean, forming a primary nitrite maximum, but can accumulate throughout the sunlit layer at higher latitudes. We model nitrifying chemoautotrophs in a marine ecosystem and demonstrate that microbial community interactions can explain the nitrite distributions. Our theoretical framework proposes that nitrite can accumulate to a higher concentration than ammonium because of differences in underlying redox chemistry and cell size between ammonia- and nitrite-oxidizing chemoautotrophs. Using ocean circulation models, we demonstrate that nitrifying microorganisms are excluded in the sunlit layer when phytoplankton are nitrogen-limited, but thrive at depth when phytoplankton become light-limited, resulting in nitrite accumulation there. However, nitrifying microorganisms may coexist in the sunlit layer when phytoplankton are iron- or light-limited (often in higher latitudes). These results improve understanding of the controls on nitrification, and provide a framework for representing chemoautotrophs and their biogeochemical effects in ocean models.
Rescue of conformational dynamics in enzyme catalysis by directed evolution
Authors: Otten Renee , Liu Lin , Kenner Lillian R. , Clarkson Michael W. , Mavor David , Tawfik Dan S. , Kern Dorothee , Fraser James S. 
Published: April 2018

AbstractRational design and directed evolution have proved to be successful approaches to increase catalytic efficiencies of both natural and artificial enzymes. Protein dynamics is recognized as important, but due to the inherent flexibility of biological macromolecules it is often difficult to distinguish which conformational changes are directly related to function. Here, we use directed evolution on an impaired mutant of the proline isomerase CypA and identify two second-shell mutations that partially restore its catalytic activity. We show both kinetically, using NMR spectroscopy, and structurally, by room-temperature X-ray crystallography, how local perturbations propagate through a large allosteric network to facilitate conformational dynamics. The increased catalysis selected for in the evolutionary screen is correlated with an accelerated interconversion between the two catalytically essential conformational sub-states, which are both captured in the high-resolution X-ray ensembles. Our data provide a glimpse of an evolutionary trajectory and show how subtle changes can fine-tune enzyme function.
A biochemical network controlling basal myosin oscillation
Authors: Qin Xiang , Hannezo Edouard , Mangeat Thomas , Liu Chang , Majumder Pralay , Liu Jiaying , Choesmel-Cadamuro Valerie , McDonald Jocelyn A. , Liu Yiyao , Yi Bin , Wang Xiaobo 
Published: April 2018

AbstractThe actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on the spatio-temporal dynamics of force generation.
Oncofetal gene SALL4 reactivation by hepatitis B virus counteracts miR-200c in PD-L1-induced T cell exhaustion
Authors: Sun Cheng , Lan Peixiang , Han Qiuju , Huang Mei , Zhang Zhihong , Xu Geliang , Song Jiaxi , Wang Jinyu , Wei Haiming , Zhang Jian , Sun Rui , Zhang Cai , Tian Zhigang 
Published: April 2018

AbstractA chronic viral or tumor microenvironment can push T cells to exhaustion by promoting coinhibitory ligand expression. However, how host factors control coinhibitory ligand expression and whether viral infection breaks this control during tumor progress is unknown. Here we show a close negative correlation between SALL4 or PD-L1 and miR-200c in tumors from 98 patients with HBV-related hepatocellular carcinoma. SALL4 or PD-L1 expression correlates negatively with miR-200c expression, and patients with lower levels of SALL4 or PD-L1 and higher miR-200c survive longer. Moreover, over-expression of miR-200c antagonizes HBV-mediated PD-L1 expression by targeting 3ʹ-UTR of CD274 (encoding PD-L1) directly, and reverses antiviral CD8+ T cell exhaustion. MiR-200c transcription is inhibited by oncofetal protein SALL4, which is re-expressed through HBV-induced STAT3 activation in adulthood. We propose that an HBV-pSTAT3-SALL4-miR-200c axis regulates PD-L1. Therapeutic strategies to influence this axis might reverse virus-induced immune exhaustion.
USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization
Authors: Yang Shangda , Liu Ling , Cao Cheng , Song Nan , Wang Yuejiao , Ma Shuai , Zhang Qi , Yu Na , Ding Xiang , Yang Fuquan , Tian Shanshan , Zhang Kai , Sun Tao , Yang Jie , Yao Zhi , Wu Shaoyuan , Shi Lei 
Published: April 2018

AbstractHistone chaperone ASF1A has been reported to be dysregulated in multiple tumors; however, the underlying molecular mechanism that how the abundance and function of ASF1A are regulated remains unclear. Here we report that ASF1A is physically associated with USP52, which is previously identified as a pseudo-deubiquitinase. Interestingly, we demonstrate that USP52 is a bona fide ubiquitin-specific protease, and USP52 promotes ASF1A deubiquitination and stabilization. USP52-promoted ASF1A stabilization facilitates chromatin assembly and favors cell cycle progression. Additionally, we find that USP52 is overexpressed in breast carcinomas, and its level of expression correlates with that of ASF1A. Moreover, we reveal that impairment of USP52-promoted ASF1A stabilization results in growth arrest of breast cancer cells and sensitizes these cells to DNA damage. Our experiments identify USP52 as a truly protein deubiquitinase, uncover a molecular mechanism of USP52 in chromatin assembly, and reveal a potential role of USP52 in breast carcinogenesis.
Asymmetric electric field screening in van der Waals heterostructures
Authors: Li Lu Hua , Tian Tian , Cai Qiran , Shih Chih-Jen , Santos Elton J. G. 
Published: April 2018

AbstractA long-standing challenge facing the combination of two-dimensional crystals into heterojunction is the unknown effect of mixing layer of different electronic properties (semiconductors, metals, insulators) on the screening features of the fabricated device platforms including their functionality. Here we use a compelling set of theoretical and experimental techniques to elucidate the intrinsic dielectric screening properties of heterostructures formed by MoS2 and graphene layers. We experimentally observed an asymmetric field screening effect relative to the polarization of the applied gate bias into the surface. Surprisingly, such behavior allows selection of the electronic states that screen external fields, and it can be enhanced with increasing of the number of layers of the semiconducting MoS2 rather than the semi-metal. This work not only provides unique insights on the screening properties of a vast amount of heterojunction fabricated so far, but also uncovers the great potential of controlling a fundamental property for device applications.
Counterregulation of cAMP-directed kinase activities controls ciliogenesis
Authors: Porpora Monia , Sauchella Simona , Rinaldi Laura , Delle Donne Rossella , Sepe Maria , Torres-Quesada Omar , Intartaglia Daniela , Garbi Corrado , Insabato Luigi , Santoriello Margherita , Bachmann Verena A. , Synofzik Matthis , Lindner Herbert H. , Conte Ivan , Stefan Eduard , Feliciello Antonio 
Published: April 2018

AbstractThe primary cilium emanates from the cell surface of growth-arrested cells and plays a central role in vertebrate development and tissue homeostasis. The mechanisms that control ciliogenesis have been extensively explored. However, the intersection between GPCR signaling and the ubiquitin pathway in the control of cilium stability are unknown. Here we observe that cAMP elevation promotes cilia resorption. At centriolar satellites, we identify a multimeric complex nucleated by PCM1 that includes two kinases, NEK10 and PKA, and the E3 ubiquitin ligase CHIP. We show that NEK10 is essential for ciliogenesis in mammals and for the development of medaka fish. PKA phosphorylation primes NEK10 for CHIP-mediated ubiquitination and proteolysis resulting in cilia resorption. Disarrangement of this control mechanism occurs in proliferative and genetic disorders. These findings unveil a pericentriolar kinase signalosome that efficiently links the cAMP cascade with the ubiquitin-proteasome system, thereby controlling essential aspects of ciliogenesis.
A semi-synthetic regulon enables rapid growth of yeast on xylose
Authors: Endalur Gopinarayanan Venkatesh , Nair Nikhil U. 
Published: April 2018

AbstractNutrient assimilation is the first step that allows biological systems to proliferate and produce value-added products. Yet, implementation of heterologous catabolic pathways has so far relied on constitutive gene expression without consideration for global regulatory systems that may enhance nutrient assimilation and cell growth. In contrast, natural systems prefer nutrient-responsive gene regulation (called regulons) that control multiple cellular functions necessary for cell survival and growth. Here, in Saccharomyces cerevisiae, by partially- and fully uncoupling galactose (GAL)-responsive regulation and metabolism, we demonstrate the significant growth benefits conferred by the GAL regulon. Next, by adapting the various aspects of the GAL regulon for a non-native nutrient, xylose, we build a semi-synthetic regulon that exhibits higher growth rate, better nutrient consumption, and improved growth fitness compared to the traditional and ubiquitous constitutive expression strategy. This work provides an elegant paradigm to integrate non-native nutrient catabolism with native, global cellular responses to support fast growth.
Pharmacologically induced amnesia for learned fear is time and sleep dependent
Authors: Kindt Merel , Soeter Marieke 
Published: April 2018

AbstractThe discovery in animal research that fear memories may change upon retrieval has sparked a wave of interest into whether this phenomenon of reconsolidation also occurs in humans. The critical conditions under which memory reconsolidation can be observed and targeted in humans, however, remain elusive. Here we report that blocking beta-adrenergic receptors in the brain, either before or after reactivation, effectively neutralizes the expression of fear memory. We show a specific time-window during which beta-adrenergic receptors are involved in the reconsolidation of fear memory. Finally, we observe intact fear memory expression 12 h after reactivation and amnesic drug intake when the retention test takes place during the same day as the intervention, but post-reactivation amnesia after a night of sleep (12 h or 24 h later). We conclude that memory reconsolidation is not simply time-dependent, but that sleep is a final and necessary link to fundamentally change the fear memory engram.
Endogenous modulation of human visual cortex activity improves perception at twilight
Authors: Cordani Lorenzo , Tagliazucchi Enzo , Vetter Céline , Hassemer Christian , Roenneberg Till , Stehle Jörg H. , Kell Christian A. 
Published: April 2018

AbstractPerception, particularly in the visual domain, is drastically influenced by rhythmic changes in ambient lighting conditions. Anticipation of daylight changes by the circadian system is critical for survival. However, the neural bases of time-of-day-dependent modulation in human perception are not yet understood. We used fMRI to study brain dynamics during resting-state and close-to-threshold visual perception repeatedly at six times of the day. Here we report that resting-state signal variance drops endogenously at times coinciding with dawn and dusk, notably in sensory cortices only. In parallel, perception-related signal variance in visual cortices decreases and correlates negatively with detection performance, identifying an anticipatory mechanism that compensates for the deteriorated visual signal quality at dawn and dusk. Generally, our findings imply that decreases in spontaneous neural activity improve close-to-threshold perception.
Valence and spin states of iron are invisible in Earth’s lower mantle
Authors: Liu Jiachao , Dorfman Susannah M. , Zhu Feng , Li Jie , Wang Yonggang , Zhang Dongzhou , Xiao Yuming , Bi Wenli , Alp E. Ercan 
Published: April 2018

AbstractHeterogeneity in Earth’s mantle is a record of chemical and dynamic processes over Earth’s history. The geophysical signatures of heterogeneity can only be interpreted with quantitative constraints on effects of major elements such as iron on physical properties including density, compressibility, and electrical conductivity. However, deconvolution of the effects of multiple valence and spin states of iron in bridgmanite (Bdg), the most abundant mineral in the lower mantle, has been challenging. Here we show through a study of a ferric-iron-only (Mg0.46Fe3+0.53)(Si0.49Fe3+0.51)O3Bdg that Fe3+in the octahedral site undergoes a spin transition between 43 and 53 GPa at 300 K. The resolved effects of the spin transition on density, bulk sound velocity, and electrical conductivity are smaller than previous estimations, consistent with the smooth depth profiles from geophysical observations. For likely mantle compositions, the valence state of iron has minor effects on density and sound velocities relative to major cation composition.