bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counterbalance: modulation of VEGF/VEGFR activities by TNFSF15
Authors: Yang Gui-Li , Li Lu-Yuan 
Published: July 2018

AbstractVascular hyperpermeability occurs in angiogenesis and several pathobiological conditions, producing elevated interstitial fluid pressure and lymphangiogenesis. How these closely related events are modulated is a fundamentally important question regarding the maintenance of vascular homeostasis and treatment of disease conditions such as cancer, stroke, and myocardial infarction. Signals mediated by vascular endothelial growth factor receptors, noticeably VEGFR-1, −2, and −3, are centrally involved in the promotion of both blood vessel and lymphatic vessel growth. These signaling pathways are counterbalanced or, in the case of VEGFR3, augmented by signals induced by tumor necrosis factor superfamily-15 (TNFSF15). TNFSF15 can simultaneously downregulate membrane-bound VEGFR1 and upregulate soluble VEGFR1, thus changing VEGF/VEGFR1 signals from pro-angiogenic to anti-angiogenic. In addition, TNFSF15 inhibits VEGF-induced VEGFR2 phosphorylation, thereby curbing VEGFR2-mediated enhancement of vascular permeability. Third, and perhaps more interestingly, TNFSF15 is capable of stimulatingVEGFR3gene expression in lymphatic endothelial cells, thus augmenting VEGF-C/D-VEGFR3-facilitated lymphangiogenesis. We discuss the intertwining relationship between the actions of TNFSF15 and VEGF in this review.
Overexpression of PEAK1 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer through modulating ERK1/2 and JAK2 signaling
Authors: Ding Chenbo , Tang Wendong , Fan Xiaobo , Wang Xiyong , Wu Hairu , Xu Hongbo , Xu Wei , Gao Wei , Wu Guoqiu 
Published: July 2018

AbstractPseudopodium-enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, has been demonstrated to act as an oncogenic regulator in breast and pancreatic cancers. However, the role of PEAK1 in the progression and metastasis of lung cancer is still unknown. Here, we observed that ectopic PEAK1 expression promoted lung cancer cell migration and invasion, while PEAK1 knockout resulted in suppressed cell migration and invasion. Interestingly, cell proliferation did not significantly increase or decrease in either the PEAK1 overexpression or knockout groups compared with the corresponding control cells. In addition, PEAK1 overexpression could induce epithelial-to-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in vivo, whereas PEAK1 knockout had the opposite effects. Then, we had confirmed that PEAK1 was significantly upregulated in lung cancer tissues, and correlated with a higher tumor node metastasis stage. Moreover, PEAK1 upregulation markedly enhanced the activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and Janus kinase-2 (JAK2) signaling in lung cancer cells. Further work demonstrated that the combination of PD98059 with AZD1480 could reverse the effects of PEAK1-induced EMT, cell migration and invasion. Our findings highlight a newer mechanism for PEAK1 in regulating EMT and metastasis in lung cancer, which might serve as a therapeutic target for lung cancer patients.
A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS- and MPTP- induced neuroinflammation
Authors: Ye Yongyi , He Xiaozheng , Lu Fengfei , Mao Hengxu , Zhu Zhiyuan , Yao Longping , Luo Wanxian , Sun Xiang , Wang Baoyan , Qian Chen , Zhang Yizhou , Lu Guohui , Zhang Shizhong 
Published: July 2018

AbstractThe role of microglial-mediated sustained neuroinflammation in the onset and progression of Parkinson’s disease (PD) is well established, but the mechanisms contributing to microglial activation remain unclear. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated. Here, we report that lincRNA-p21 promotes microglial activation through a p53-dependent transcriptional pathway. We further demonstrate that lincRNA-p21 competitively binds to the miR-181 family and induces microglial activation through the miR-181/PKC-δ pathway. Moreover, PKC-δ induction further increases the expression of p53/lincRNA-p21 and thus forms a circuit. Taken together, our results suggest that p53/lincRNA-p21, together with miR-181/PKC-δ, form a double-negative feedback loop that facilitates sustained microglial activation and the deterioration of neurodegeneration.
ZDHHC8 critically regulates seizure susceptibility in epilepsy
Authors: Yang Qin , Zheng Fangshuo , Hu Yida , Yang Yi , Li Yun , Chen Guojun , Wang Wei , He Miaoqing , Zhou Ruijiao , Ma Yuanlin , Xu Demei , Tian Xin , Gao Xiaoya , Wang Qing , Wang Xuefeng 
Published: July 2018

AbstractEpilepsy is one of the most prevalent and drug-refractory neurological disorders. Zinc finger DHHC-type containing 8 (ZDHHC8) is a putative palmitoyltransferase that is highly expressed in the brain. However, the impact of ZDHHC8 on seizures remains unclear. We aimed to explore the association of ZDHHC8 with epilepsy and investigate its in epileptogenesis in in vivo and in vitro models through behavioral, electrophysiological, and pathological studies. We used kainic acid- and pilocarpine-induced C57BL/6 mice and magnesium-free-induced pyramidal neurons as experimental epileptic models in this study. We first found increased ZDHHC8 expression in the brains of temporal lobe epilepsy (TLE) patients, similar to that observed in chronic epileptic mice, strongly suggesting that ZDHHC8 is correlated with human epilepsy. In the in vitro seizure models, knocking down ZDHHC8 using recombinant adeno-associated virus (rAAV) delayed seizure precipitation and decreased chronic spontaneous recurrent seizures (SRSs) and epileptiform-like discharges, while ZDHHC8 overexpression had the opposite effect. ZDHHC8 levels were consistent with seizure susceptibility in induced mice with SRSs. In an in vitro magnesium-free model, neuronal hyperexcitability and hypersynchrony were reduced in ZDHHC8-knockdown neurons but were increased in ZDHHC8-overexpressing neurons. To further explore the potential mechanisms, we observed that ZDHHC8 had a significant modulatory effect on 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-related excitatory, but not inhibitory, glutamatergic synaptic neurotransmission, further affecting the inward rectification of AMPA currents in acute hippocampal slices in whole-cell recordings. ZDHHC8 facilitated GluA1 trafficking to the neuronal surface in the hippocampus, as shown by immunoprecipitation and Western blotting. These results suggest that ZDHHC8 may promote the generation and propagation of seizures in humans and that knocking down ZDHHC8 might produce anti-epileptogenic effects in drug-resistant epilepsy. Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.
Programmable DNA repair with CRISPRa/i enhanced homology-directed repair efficiency with a single Cas9
Authors: Ye Lupeng , Wang Chengkun , Hong Lingjuan , Sun Ninghe , Chen Danyang , Chen Sidi , Han Feng 
Published: July 2018

AbstractCRISPR systems have been proven as versatile tools for site-specific genome engineering in mammalian species. During the gene editing processes, these RNA-guide nucleases introduce DNA double strand breaks (DSBs), in which non-homologous DNA end joining (NHEJ) dominates the DNA repair pathway, limiting the efficiency of homology-directed repair (HDR), the alternative pathway essential for precise gene targeting. Multiple approaches have been developed to enhance HDR, including chemical compound or RNA interference-mediated inhibition of NHEJ factors, small molecule activation of HDR enzymes, or cell cycle timed delivery of CRISPR complex. However, these approaches face multiple challenges, yet have moderate or variable effects. Here we developed a new approach that programs both NHEJ and HDR pathways with CRISPR activation and interference (CRISPRa/i) to achieve significantly enhanced HDR efficiency of CRISPR-mediated gene editing. The manipulation of NHEJ and HDR pathway components, such as CtIP, CDK1, KU70, KU80, and LIG4, was mediated by catalytically dead guide RNAs (dgRNAs), thus relying on only a single catalytically active Cas9 to perform both CRISPRa/i and precise gene editing. While reprogramming of most DNA repair factors or their combinations tested enhanced HDR efficiency, simultaneously activating CDK1 and repressing KU80 has the strongest effect with increased HDR rate upto an order of magnitude. Doxycycline-induced dgRNA-based CRISPRa/i programming of DNA repair enzymes, as well as viral packaging enabled flexible and tunable HDR enhancement for broader applicability in mammalian cells. Our study provides an effective, flexible, and potentially safer strategy to enhance precise genome modifications, which might broadly impact human gene editing and therapy.
Operando and three-dimensional visualization of anion depletion and lithium growth by stimulated Raman scattering microscopy
Authors: Cheng Qian , Wei Lu , Liu Zhe , Ni Nan , Sang Zhe , Zhu Bin , Xu Weiheng , Chen Meijie , Miao Yupeng , Chen Long-Qing , Min Wei , Yang Yuan 
Published: July 2018

AbstractVisualization of ion transport in electrolytes provides fundamental understandings of electrolyte dynamics and electrolyte-electrode interactions. However, this is challenging because existing techniques are hard to capture low ionic concentrations and fast electrolyte dynamics. Here we show that stimulated Raman scattering microscopy offers required resolutions to address a long-lasting question: how does the lithium-ion concentration correlate to uneven lithium deposition? In this study, anions are used to represent lithium ions since their concentrations should not deviate for more than 0.1 mM, even near nanoelectrodes. A three-stage lithium deposition process is uncovered, corresponding to no depletion, partial depletion, and full depletion of lithium ions. Further analysis reveals a feedback mechanism between the lithium dendrite growth and heterogeneity of local ionic concentration, which can be suppressed by artificial solid electrolyte interphase. This study shows that stimulated Raman scattering microscopy is a powerful tool for the materials and energy field.
Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production
Authors: Amini Poorya , Stojkov Darko , Felser Andrea , Jackson Christopher B. , Courage Carolina , Schaller André , Gelman Laurent , Soriano Maria Eugenia , Nuoffer Jean-Marc , Scorrano Luca , Benarafa Charaf , Yousefi Shida , Simon Hans-Uwe 
Published: July 2018

AbstractOptic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1N∆), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD+ availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1N∆ mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.
Mechanical dissipation from charge and spin transitions in oxygen-deficient SrTiO3 surfaces
Authors: Kisiel Marcin , Brovko Oleg O. , Yildiz Dilek , Pawlak Rémy , Gysin Urs , Tosatti Erio , Meyer Ernst 
Published: July 2018

AbstractBodies in relative motion separated by a gap of a few nanometers can experience a tiny friction force. This non-contact dissipation can have various origins and can be successfully measured by a sensitive pendulum atomic force microscope tip oscillating laterally above the surface. Here, we report on the observation of dissipation peaks at selected voltage-dependent tip-surface distances for oxygen-deficient strontium titanate (SrTiO3) surface at low temperatures (T = 5 K). The observed dissipation peaks are attributed to tip-induced charge and spin state transitions in quantum-dot-like entities formed by single oxygen vacancies (and clusters thereof, possibly through a collective mechanism) at the SrTiO3 surface, which in view of technological and fundamental research relevance of the material opens important avenues for further studies and applications.
A user-friendly herbicide derived from photo-responsive supramolecular vesicles
Authors: Gao Cheng , Huang Qiaoxian , Lan Qingping , Feng Yu , Tang Fan , Hoi Maggie P. M. , Zhang Jianxiang , Lee Simon M. Y. , Wang Ruibing 
Published: July 2018

AbstractParaquat, as one of the most widely used herbicides globally, is highly toxic to humans, and chronic exposure and acute ingestion leads to high morbidity and mortality rates. Here, we report user-friendly, photo-responsive paraquat-loaded supramolecular vesicles, prepared via one-pot self-assembly of amphiphilic, ternary host-guest complexes between cucurbit[8]uril, paraquat, and an azobenzene derivative. In this vesicle formulation, paraquat is only released upon UV or sunlight irradiation that converts the azobenzene derivative from its trans- to its cis- form, which in turn dissociates the ternary host-guest complexations and the vesicles. The cytotoxicity evaluation of this vesicle formulation of paraquat on in vitro cell models, in vivo zebrafish models, and mouse models demonstrates an enhanced safety profile. Additionally, the PQ-loaded vesicles’ herbicidal activity against a model of invasive weed is nearly identical to that of free paraquat under natural sunlight. This study provides a safe yet effective herbicide formulation.
Nanometer-scale gradient atomic packing structure surrounding soft spots in metallic glasses
Authors: Wang Binbin , Luo Liangshun , Guo Enyu , Su Yanqing , Wang Mingyue , Ritchie Robert O. , Dong Fuyu , Wang Liang , Guo Jingjie , Fu Hengzhi 
Published: July 2018

AbstractThe hidden order of atomic packing in amorphous structures and how this may provide the origin of plastic events have long been a goal in the understanding of plastic deformation in metallic glasses. To pursue this issue, we employ here molecular dynamic simulations to create three-dimensional models for a few metallic glasses where, based on the geometrical frustration of the coordination polyhedra, we classify the atoms in the amorphous structure into six distinct species, where “gradient atomic packing structure” exists. The local structure in the amorphous state can display a gradual transition from loose stacking to dense stacking of atoms, followed by a gradient evolution of atomic performance. As such, the amorphous alloy specifically comprises three discernible regions: solid-like, transition, and liquid-like regions, each one possessing different types of atoms. We also demonstrate that the liquid-like atoms correlate most strongly with fertile sites for shear transformation, the transition atoms take second place, whereas the solid-like atoms contribute the least because of their lowest correlation level with the liquid-like atoms. Unlike the “geometrically unfavored motifs” model which fails to consider the role of medium-range order, our model gives a definite structure for the so-called “soft spots”, that is, a combination of liquid-like atoms and their neighbors, in favor of quantifying and comparing their number between different metallic glasses, which can provide a rational explanation for the unique mechanical behavior of metallic glasses.
Nondestructive detector for exchange symmetry of photonic qubits
Authors: Stárek Robert , Mičuda Michal , Miková Martina , Straka Ivo , Dušek Miloslav , Marek Petr , Ježek Miroslav , Filip Radim , Fiurášek Jaromír 
Published: July 2018

AbstractWe experimentally realize a quantum Fredkin gate and use it for constructing a nondestructive detector of exchange symmetry for qubits. The detector, which discriminates between symmetric and anti-symmetric quantum states of two qubits, allows us to directly measure a purity and overlap of quantum states and implement a quantum state programmable measurement. Furthermore, the nondestructive nature of the detector can be used for analysis of the back-action of the measurements, as well as for realization of nonlinear quantum operations, such as quantum purification and quantum cloning. As a whole, the experiment demonstrates the utility of exchange symmetry measurements and their potential for multi-step characterization and processing of quantum states.
Matrine inhibits itching by lowering the activity of calcium channel
Authors: Geng Xiao , Shi Hao , Ye Fan , Du Han , Qian Linnan , Gu Leying , Wu Guanyi , Zhu Chan , Yang Yan , Wang Changming , Zhou Yuan , Yu Guang , Liu Qin , Dong Xinzhong , Yu Lei , Tang Zongxiang 
Published: July 2018

AbstractSophorae Flavescentis Radix(SFR) is a medicinal herb with many functions that are involved in anti-inflammation, antinociception, and anticancer.SFRis also used to treat a variety of itching diseases. Matrine (MT) is one of the main constituents in SFR and also has the effect of relieving itching, but the antipruritic mechanism is still unclear. Here, we investigated the effect of MT on anti-pruritus. In acute and chronic itch models, MT significantly inhibited the scratching behavior not only in acute itching induced by histamine (His), chloroquine (CQ) and compound 48/80 with a dose-depended manner, but also in the chronic pruritus models of atopic dermatitis (AD) and acetone-ether-water (AEW) in mice. Furthermore, MT could be detected in the blood after intraperitoneal injection (i.p.) and subcutaneous injection (s.c.). Finally, electrophysiological and calcium imaging results showed that MT inhibited the excitatory synaptic transmission from dorsal root ganglion (DRG) to the dorsal horn of the spinal cord by suppressing the presynaptic N-type calcium channel. Taken together, we believe that MT is a novel drug candidate in treating pruritus diseases, especially for histamine-independent and chronic pruritus, which might be attributed to inhibition of the presynaptic N-type calcium channel.
Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy
Authors: Napoli Eleonora , Song Gyu , Panoutsopoulos Alexios , Riyadh M. Asrafuzzaman , Kaushik Gaurav , Halmai Julian , Levenson Richard , Zarbalis Konstantinos S. , Giulivi Cecilia 
Published: July 2018

AbstractWD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3+/lacZ mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood. We found that Wdfy3 is required for sustaining brain bioenergetics and morphology via mitophagy. Decreased mitochondrial quality control by conventional mitophagy was partly compensated for by the increased formation of mitochondria-derived vesicles (MDV) targeted to lysosomal degradation (micromitophagy). These observations, extended through proteomic analysis of mitochondria-enriched cortical fractions, showed significant enrichment for pathways associated with mitophagy, mitochondrial transport and axon guidance via semaphorin, Robo, L1cam and Eph-ephrin signaling. Collectively, our findings support a critical role for Wdfy3 in mitochondrial homeostasis with implications for neuron differentiation, neurodevelopment and age-dependent neurodegeneration.
Streptozotocin-induced β-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain
Authors: Nikolakopoulou Polyxeni , Chatzigeorgiou Antonios , Kourtzelis Ioannis , Toutouna Louiza , Masjkur Jimmy , Arps-Forker Carina , Poser Steven W. , Rozman Jan , Rathkolb Birgit , Aguilar-Pimentel Juan Antonio ,   German Mouse Clinic Consortium, Becker Lore , Klopstock Thomas , Treise Irina , Busch Dirk H. , Beckers Johannes , Moreth Kristin , Bekeredjian Raffi , Garrett Lillian , Hölter Sabine M. , Zimprich Annemarie , Wurst Wolfgang , Brommage Robert , Amarie Oana , Graw Jochen , Calzada-Wack Julia , Neff Frauke , Zimmer Andreas , Östereicher Manuela , Steinkamp Ralph , Lengger Christoph , Maier Holger , Stoeger Claudia , Leuchtenberger Stefanie , Wolf Eckhard , Klingenspor Martin , Ollert Markus , Schmidt-Weber Carsten , Fuchs Helmut , Gailus-Durner Valerie , Hrabe de Angelis Martin , Tsata Vasiliki , Monasor Laura Sebastian , Troullinaki Maria , Witt Anke , Anastasiou Vivian , Chrousos George , Yi Chun-Xia , García-Cáceres Cristina , Tschöp Matthias H. , Bornstein Stefan R. , Androutsellis-Theotokis Andreas 
Published: July 2018

AbstractDiabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise; it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced β-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus.