bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-κB and β-catenin/TCF signaling pathways
Authors: Wang Lina , Feng Wenli , Yang Xiao , Yang Feifei , Wang Rong , Ren Qian , Zhu Xiaofan , Zheng Guoguang 
Published: April 2018

AbstractThe ubiquitin–proteasome system (UPS) participates in both physiological and pathological processes through the posttranslational regulation of intracellular signal transduction pathways. F-box and WD-40 domain protein 11 (Fbxw11) is a component of the SCF (Skp1–Cul1–F-box) E3 ubiquitin ligase complex. Fbxw11 regulates various signal transduction pathways, and it may have pathological roles in tumorigenesis. However, the role of Fbxw11 in the development of leukemia and the underlying mechanisms remain largely unknown. In this study, Fbxw11 expression was aberrantly upregulated in patients with lymphocytic leukemia. Its expression was dramatically decreased in patients who achieved complete remission (CR) after chemotherapy. The high level of Fbxw11 expression in L1210 lymphocytic leukemia cells stimulated cell proliferation in vitro and tumor formation in vivo. The effects were mediated by the stimulation of cell cycle progression rather than the induction of apoptosis. Furthermore, a bioinformatics analysis suggested concomitant activation of the NF-κB and β-catenin/TCF signaling pathways, which were confirmed by reporter gene assays. Moreover, blocking experiments suggested the involvement of both pathways in the growth-promoting effects of Fbxw11. Our results reveal the role of Fbxw11 in lymphocytic leukemia cells and imply that Fbxw11 may serve as a potential molecular target for the treatment of lymphocytic leukemia.
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer
Authors: Gao Yuan , Li Xiaoju , Shu Zhen , Zhang Kuo , Xue Xiaochang , Li Weina , Hao Qiang , Wang Zhaowei , Zhang Wangqian , Wang Shuning , Zeng Cheng , Fan Dong , Zhang Wei , Zhang Yingqi , Zhao Huadong , Li Meng , Zhang Cun 
Published: April 2018

AbstractFOXP3 is an important X-linked suppressor of breast cancer. It is reported that FOXP3 is usually mutant, absent, or cytoplasmic distribution in breast cancer cells, which increases the risk of breast cancer. However, in our study the full-length FOXP3 transcript can be detected in breast cancer cells and nuclear FOXP3 is expressed in some breast cancer samples. Therefore, an important question is how the tumor-suppressive function of wild-type FOXP3 is negated in these cancers. We found that Gal-1 is a novel interacting protein of FOXP3 in breast cancer. Furthermore, our results show that the FKH domain in FOXP3 is essential for its interaction with Gal-1. Through ChIP-seq assay, we found that the expression of Gal-1 could inhibit a variety of target genes which were directly regulated by FOXP3. More importantly, these FOXP3-bound genes are involved in the development and metastasis of cancer. Furthermore, functional studies revealed that blocking the FOXP3/Gal-1 interaction restores the tumor-suppressive properties of FOXP3 in breast cancer cells. Finally, we observed that the nuclear abundance of Gal-1 was significantly higher in breast cancer tissues than that in adjacent normal tissues. In addition, we identified that the acidic extracellular microenvironment in breast cancer tissues causes Gal-1 to accumulate in the nucleus. Altogether, nuclear Gal-1 interferes with the binding of FOXP3 to DNA by interacting with the FKH domain of FOXP3, and it indicates a possible mechanism for the loss of the tumor-suppressive properties of FOXP3 in wild-type FOXP3-positive breast cancer.
Taurine protects dopaminergic neurons in a mouse Parkinson’s disease model through inhibition of microglial M1 polarization
Authors: Che Yuning , Hou Liyan , Sun Fuqiang , Zhang Cong , Liu Xiaofang , Piao Fengyuan , Zhang Dan , Li Huihua , Wang Qingshan 
Published: April 2018

AbstractMicroglia-mediated neuroinflammation is implicated in multiple neurodegenerative disorders, including Parkinson’s disease (PD). Hence, the modulatioein of sustained microglial activation may have therapeutic potential. This study is designed to test the neuroprotective efficacy of taurine, a major intracellular free β-amino acid in mammalian tissues, by using paraquat and maneb-induced PD model. Results showed that mice intoxicated with paraquat and maneb displayed progressive dopaminergic neurodegeneration and motor deficits, which was significantly ameliorated by taurine. Taurine also attenuated the aggregation of α-synuclein in paraquat and maneb-intoxicated mice. Mechanistically, taurine suppressed paraquat and maneb-induced microglial activation. Moreover, depletion of microglia abrogated the dopaminergic neuroprotective effects of taurine, revealing the role of microglial activation in taurine-afforded neuroprotection. Subsequently, we found that taurine suppressed paraquat and maneb-induced microglial M1 polarization and gene expression levels of proinflammatory factors. Furthermore, taurine was shown to be able to inhibit the activation of NADPH oxidase (NOX2) by interfering with membrane translocation of cytosolic subunit, p47phox and nuclear factor-kappa B (NF-κB) pathway, two key factors for the initiation and maintenance of M1 microglial inflammatory response. Altogether, our results showed that taurine exerted dopaminergic neuroprotection through inactivation of microglia-mediated neuroinflammation, providing a promising avenue and candidate for the potential therapy for patients suffering from PD.
Macrophage inducible nitric oxide synthase circulates inflammation and promotes lung carcinogenesis
Authors: Wang Xin , Gray Zane , Willette-Brown Jami , Zhu Feng , Shi Gongping , Jiang Qun , Song Na-Young , Dong Liang , Hu Yinling 
Published: April 2018

AbstractHuman lung squamous cell carcinoma (SCC) is highly associated with increased pulmonary macrophage infiltration. Previously, we showed that marked pulmonary infiltrating macrophages were required for spontaneous lung SCC development in a mouse model (L-Ikkα
KA/KA
, KA/KA) that resembles human lung SCC. Interestingly the lung SCC-associated macrophages specifically express elevated inducible nitric oxide synthase (NOS2). However, the role of macrophage NOS2 in lung carcinogenesis has not been explored. Here, we show that NOS2 ablation inhibits macrophage infiltration, fibrosis, and SCC development in the lungs of KA/KA mice. Macrophage NOS2 was found to circulate inflammation and enhance macrophage migration and survival. NOS2 promotes foamy macrophage formation characterized with impaired lipid metabolism. NOS2 null bone marrow transplantation reduces foamy macrophage numbers and carcinogenesis in KA/KA chimaeras. This finding sheds light on a new mechanism by which macrophage NOS2 increases pulmonary inflammatory responses and macrophage survival and impairs macrophage lipid metabolism, thereby promoting lung SCC formation.
Chasing the signaling run by tri-molecular time-lapse FRET microscopy
Authors: Kuo Hsiang-Ling , Ho Pei-Chuan , Huang Shenq-Shyang , Chang Nan-Shan 
Published: April 2018

AbstractA feasible design is made to measure three protein/protein interactions to visualize signal pathways by time-lapse Förster resonance energy transfer (FRET) microscopy. When interacting proteins are in close proximity, excitation energy is provided to allow the energy flow from the first molecule to excite the second, followed by energy transfer to the third. By phorbol ester/calcium ionophore stimulation, for example, a real-time complex formation of ectopic IκBα/ERK/WWOX occurs as measured by FRET microscopy, indicative of an ongoing functional signaling. Hyaluronan induces membrane Hyal-2 signaling, which allows FRET measurement of the complex formation of ectopic Smad4/WWOX/Hyal-2 for causing bubbling cell death. If ectopic p53 is recruited to replace Hyal-2, the resulting ectopic Smad4/WWOX/p53 complex induces membrane blebbing without cell death. Together, in this perspective review article, we demonstrate the utilization of time-lapse FRET microscopy to visualize the signaling event via the tri-molecular protein complex formation and their biological outcomes. We show an initial two-protein binding to form the driving force to jumpstart the tri-molecular execution for the signal pathway.
Large-area and bright pulsed electroluminescence in monolayer semiconductors
Authors: Lien Der-Hsien , Amani Matin , Desai Sujay B. , Ahn Geun Ho , Han Kevin , He Jr-Hau , Ager Joel W. , Wu Ming C. , Javey Ali 
Published: April 2018

AbstractTransition-metal dichalcogenide monolayers have naturally terminated surfaces and can exhibit a near-unity photoluminescence quantum yield in the presence of suitable defect passivation. To date, steady-state monolayer light-emitting devices suffer from Schottky contacts or require complex heterostructures. We demonstrate a transient-mode electroluminescent device based on transition-metal dichalcogenide monolayers (MoS2, WS2, MoSe2, and WSe2) to overcome these problems. Electroluminescence from this dopant-free two-terminal device is obtained by applying an AC voltage between the gate and the semiconductor. Notably, the electroluminescence intensity is weakly dependent on the Schottky barrier height or polarity of the contact. We fabricate a monolayer seven-segment display and achieve the first transparent and bright millimeter-scale light-emitting monolayer semiconductor device.
Mechanistic insights into allosteric regulation of the A2A adenosine G protein-coupled receptor by physiological cations
Authors: Ye Libin , Neale Chris , Sljoka Adnan , Lyda Brent , Pichugin Dmitry , Tsuchimura Nobuyuki , Larda Sacha T. , Pomès Régis , García Angel E. , Ernst Oliver P. , Sunahara Roger K. , Prosser R. Scott 
Published: April 2018

AbstractCations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here,19F NMR is used to delineate the effects of cations on functional states of the adenosine A2AGPCR. While Na+reinforces an inactive ensemble and a partial-agonist stabilized state, Ca2+and Mg2+shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridge specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. An understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu.
A licensing step links AID to transcription elongation for mutagenesis in B cells
Authors: Methot Stephen P. , Litzler Ludivine C. , Subramani Poorani Ganesh , Eranki Anil K. , Fifield Heather , Patenaude Anne-Marie , Gilmore Julian C. , Santiago Gabriel E. , Bagci Halil , Côté Jean-François , Larijani Mani , Verdun Ramiro E. , Di Noia Javier M. 
Published: April 2018

AbstractActivation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID mutates a few hundred other loci, but most AID-occupied genes are spared. The mechanisms underlying productive deamination versus non-productive AID targeting are unclear. Here we show that three clustered arginine residues define a functional AID domain required for SHM, CSR, and off-target activity in B cells without affecting AID deaminase activity or Escherichia coli mutagenesis. Both wt AID and mutants with single amino acid replacements in this domain broadly associate with Spt5 and chromatin and occupy the promoter of AID target genes. However, mutant AID fails to occupy the corresponding gene bodies and loses association with transcription elongation factors. Thus AID mutagenic activity is determined not by locus occupancy but by a licensing mechanism, which couples AID to transcription elongation.
Designable ultra-smooth ultra-thin solid-electrolyte interphases of three alkali metal anodes
Authors: Gu Yu , Wang Wei-Wei , Li Yi-Juan , Wu Qi-Hui , Tang Shuai , Yan Jia-Wei , Zheng Ming-Sen , Wu De-Yin , Fan Chun-Hai , Hu Wei-Qiang , Chen Zhao-Bin , Fang Yuan , Zhang Qing-Hong , Dong Quan-Feng , Mao Bing-Wei 
Published: April 2018

AbstractDendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm–2 with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.
Cell-free protein synthesis from genomically recoded bacteria enables multisite incorporation of noncanonical amino acids
Authors: Martin Rey W. , Des Soye Benjamin J. , Kwon Yong-Chan , Kay Jennifer , Davis Roderick G. , Thomas Paul M. , Majewska Natalia I. , Chen Cindy X. , Marcum Ryan D. , Weiss Mary Grace , Stoddart Ashleigh E. , Amiram Miriam , Ranji Charna Arnaz K. , Patel Jaymin R. , Isaacs Farren J. , Kelleher Neil L. , Hong Seok Hoon , Jewett Michael C. 
Published: April 2018

AbstractCell-free protein synthesis has emerged as a powerful approach for expanding the range of genetically encoded chemistry into proteins. Unfortunately, efforts to site-specifically incorporate multiple non-canonical amino acids into proteins using crude extract-based cell-free systems have been limited by release factor 1 competition. Here we address this limitation by establishing a bacterial cell-free protein synthesis platform based on genomically recoded Escherichia coli lacking release factor 1. This platform was developed by exploiting multiplex genome engineering to enhance extract performance by functionally inactivating negative effectors. Our most productive cell extracts enabled synthesis of 1,780 ± 30 mg/L superfolder green fluorescent protein. Using an optimized platform, we demonstrated the ability to introduce 40 identical p-acetyl-l-phenylalanine residues site specifically into an elastin-like polypeptide with high accuracy of incorporation ( ≥ 98%) and yield (96 ± 3 mg/L). We expect this cell-free platform to facilitate fundamental understanding and enable manufacturing paradigms for proteins with new and diverse chemistries.
Engineering enhanced cellobiohydrolase activity
Authors: Taylor Larry E. , Knott Brandon C. , Baker John O. , Alahuhta P. Markus , Hobdey Sarah E. , Linger Jeffrey G. , Lunin Vladimir V. , Amore Antonella , Subramanian Venkataramanan , Podkaminer Kara , Xu Qi , VanderWall Todd A. , Schuster Logan A. , Chaudhari Yogesh B. , Adney William S. , Crowley Michael F. , Himmel Michael E. , Decker Stephen R. , Beckham Gregg T. 
Published: April 2018

AbstractGlycoside Hydrolase Family 7 cellobiohydrolases (GH7 CBHs) catalyze cellulose depolymerization in cellulolytic eukaryotes, making them key discovery and engineering targets. However, there remains a lack of robust structure–activity relationships for these industrially important cellulases. Here, we compare CBHs from Trichoderma reesei (TrCel7A) and Penicillium funiculosum (PfCel7A), which exhibit a multi-modular architecture consisting of catalytic domain (CD), carbohydrate-binding module, and linker. We show that PfCel7A exhibits 60% greater performance on biomass than TrCel7A. To understand the contribution of each domain to this improvement, we measure enzymatic activity for a library of CBH chimeras with swapped subdomains, demonstrating that the enhancement is mainly caused by PfCel7A CD. We solve the crystal structure of PfCel7A CD and use this information to create a second library of TrCel7A CD mutants, identifying a TrCel7A double mutant with near-equivalent activity to wild-type PfCel7A. Overall, these results reveal CBH regions that enable targeted activity improvements.
Silicon and glass very large scale microfluidic droplet integration for terascale generation of polymer microparticles
Authors: Yadavali Sagar , Jeong Heon-Ho , Lee Daeyeon , Issadore David 
Published: April 2018

AbstractMicrofluidic chips can generate emulsions, which can be used to synthesize polymer microparticles that have superior pharmacological performance compared to particles prepared by conventional techniques. However, low production rates of microfluidics remains a challenge to successfully translate laboratory discoveries to commercial manufacturing. We present a silicon and glass device that incorporates an array of 10,260 (285 × 36) microfluidic droplet generators that uses only a single set of inlets and outlets, increasing throughput by >10,000× compared to microfluidics with a single generator. Our design breaks the tradeoff between the number of generators and the maximum throughput of individual generators by incorporating high aspect ratio flow resistors. We test these design strategies by generating hexadecane microdroplets at >1 trillion droplets per h with a coefficient of variation CV <3%. To demonstrate the synthesis of biocompatible microparticles, we generated 8–16 µm polycaprolactone particles with a CV <5% at a rate of 277 g h−1.
Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase
Authors: Navarro Gemma , Cordomí Arnau , Casadó-Anguera Verónica , Moreno Estefanía , Cai Ning-Sheng , Cortés Antoni , Canela Enric I. , Dessauer Carmen W. , Casadó Vicent , Pardo Leonardo , Lluís Carme , Ferré Sergi 
Published: April 2018

AbstractG protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A2A receptor and dopamine D2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.
Low ocean-floor rises regulate subpolar sea surface temperature by forming baroclinic jets
Authors: Mitsudera H. , Miyama T. , Nishigaki H. , Nakanowatari T. , Nishikawa H. , Nakamura T. , Wagawa T. , Furue R. , Fujii Y. , Ito S. 
Published: April 2018

AbstractSea surface temperature (SST) fronts in mid- to high-latitude oceans have significant impacts on extratropical atmospheric circulations and climate. In the western subarctic Pacific, sharp SST fronts form between the cold subarctic water and the recently found quasi-stationary jets that advect warm waters originating in the Kuroshio northeastward. Here we present a new mechanism of the jet formation paying attention to the propagation of baroclinic Rossby waves that is deflected by eddy-driven barotropic flows over bottom rises, although their height is low (~500 m) compared with the depth of the North Pacific Ocean (~6000 m). Steered by the barotropic flows, Rossby waves bring a thicker upper layer from the subtropical gyre and a thinner upper layer from the subarctic gyre, thereby creating a thickness jump, hence a surface jet, where they converge. This study reveals an overlooked role of low-rise bottom topography in regulating SST anomalies in subpolar oceans.
Impact of evolving greenhouse gas forcing on the warming signal in regional climate model experiments
Authors: Jerez S. , López-Romero J. M. , Turco M. , Jiménez-Guerrero P. , Vautard R. , Montávez J. P. 
Published: April 2018

AbstractVariations in the atmospheric concentrations of greenhouse gases (GHG) may not be included as external forcing when running regional climate models (RCMs); at least, this is a non-regulated, non-documented practice. Here we investigate the so far unexplored impact of considering the rising evolution of the CO2, CH4, and N2O atmospheric concentrations on near-surface air temperature (TAS) trends, for both the recent past and the near future, as simulated by a state-of-the-art RCM over Europe. The results show that the TAS trends are significantly affected by 1–2 K century−1, which under 1.5 °C global warming translates into a non-negligible impact of up to 1 K in the regional projections of TAS, similarly affecting projections for maximum and minimum temperatures. In some cases, these differences involve a doubling signal, laying further claim to careful reconsideration of the RCM setups with regard to the inclusion of GHG concentrations as an evolving external forcing which, for the sake of research reproducibility and reliability, should be clearly documented in the literature.
Asymmetric synthesis of γ-branched amines via rhodium-catalyzed reductive amination
Authors: Wu Zhao , Laffoon Summer D. , Hull Kami L. 
Published: April 2018

AbstractAmines bearing γ-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral γ-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents, which allows for a rapid and modular synthesis of many chiral γ-branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity.