bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms
Authors: Wolfsperger F , Hogh-Binder S A , Schittenhelm J , Psaras T , Ritter V , Bornes L , Huber S M , Jendrossek V , Rudner J 
Published: January 2016

AbstractGlioblastoma is a very aggressive form of brain tumor with limited therapeutic options. Usually, glioblastoma is treated with ionizing radiation (IR) and chemotherapy after surgical removal. However, radiotherapy is frequently unsuccessful, among others owing to resistance mechanisms the tumor cells have developed. Antiapoptotic B-cell leukemia (Bcl)-2 family members can contribute to radioresistance by interfering with apoptosis induction in response to IR. Bcl-2 and the closely related Bcl-xL and Mcl-1 are often overexpressed in glioblastoma cells. In contrast to Bcl-2 and Bcl-xL, Mcl-1 is a short-lived protein whose stability is closely regulated by ubiquitylation-dependent proteasomal degradation. Although ubiquitin ligases facilitate degradation, the deubiquitylating enzyme ubiquitin-specific protease 9x (USP9x) interferes with degradation by removing polyubiquitin chains from Mcl-1, thereby stabilizing this protein. Thus, an inability to downregulate Mcl-1 by enhanced USP9x activity might contribute to radioresistance. Here we analyzed the impact of USP9x on Mcl-1 levels and radiosensitivity in glioblastoma cells. Correlating Mcl-1 and USP9x expressions were significantly higher in human glioblastoma than in astrocytoma. Downregulation of Mcl-1 correlated with apoptosis induction in established glioblastoma cell lines. Although Mcl-1 knockdown by siRNA increased apoptosis induction after irradiation in all glioblastoma cell lines, USP9x knockdown significantly improved radiation-induced apoptosis in one of four cell lines and slightly increased apoptosis in another cell line. In the latter two cell lines, USP9x knockdown also increased radiation-induced clonogenic death. The massive downregulation of Mcl-1 and apoptosis induction in A172 cells transfected with USP9x siRNA shows that the deubiquitinase regulates cell survival by regulating Mcl-1 levels. In contrast, USP9x regulated radiosensitivity in Ln229 cells without affecting Mcl-1 levels. We conclude that USP9x can control survival and radiosensitivity in glioblastoma cells by Mcl-1-dependent and Mcl-1-independent mechanisms.
EMC6/TMEM93 suppresses glioblastoma proliferation by modulating autophagy
Authors: Shen X , Kan S , Hu J , Li M , Lu G , Zhang M , Zhang S , Hou Y , Chen Y , Bai Y 
Published: January 2016

AbstractEMC6 (endoplasmic reticulum membrane protein complex subunit 6), also known as transmembrane protein 93, is a novel positive autophagy regulator. In this report, we evaluated the anti-tumor activity of EMC6 in glioblastoma cells in vitro and in vivo. Our data show that overexpression of EMC6 in three glioblastoma cell lines (SHG44, U87 and U251) suppresses tumor cell growth by activating autophagy, but fails to induce cell apoptosis. EMC6-mediated autophagy was associated with inactivation of the PIK3CA/AKT/mTOR signaling pathway. Accordingly, EMC6 knockdown in glioblastoma cells had the opposite effect; it promoted cell growth. Overexpression of EMC6 also sensitized glioblastoma cells to the chemotherapy drug, temozolomide, to further suppress tumor growth. Our data indicate that EMC6-induced autophagy may play a positive role in suppressing the development of glioblastoma.
Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice
Authors: Wang L , Jiang Y , Song X , Guo C , Zhu F , Wang X , Wang Q , Shi Y , Wang J , Gao F , Zhao W , Chen Y H , Zhang L 
Published: January 2016

AbstractMacrophage foam cells, a major component of the atherosclerotic lesion, have vital roles in the development of atherosclerosis. Lipoautophagy, a type of autophagy characterized by selective delivery of lipid droplet for lysosomal degradation, may impact atherosclerosis by regulating macrophage foam cell formation. Previously, we reported that programmed cell death 4 (PDCD4), a tumor suppressor, negatively regulated autophagy in tumor cells. However, its roles in macrophage lipoautophagy, foam cell formation and atherosclerosis remain to be established. Here we found that Pdcd4 deficiency clearly improved oxidized low-density lipoproteins-impaired autophagy efflux, promoted autophagy-mediated lipid breakdown in murine macrophages and thus prevented macrophage conversion into foam cells. Importantly, Pdcd4 deficiency in mice significantly upregulated macrophage autophagy in local plaques along with attenuated lipid accumulation and atherosclerotic lesions in high-fat-fed Apolipoprotein E knockout mice. Bone marrow transplantation experiment demonstrated that PDCD4-mediated autophagy in hematopoietic cells contributed to the development of atherosclerosis. These results indicate that endogenous PDCD4 promotes for macrophage foam cell formation and atherosclerosis development via inhibiting autophagy and provides new insights into atherogenesis, suggesting that promoting macrophage autophagy through downregulating PDCD4 expression may be beneficial for treating atherosclerosis.
Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction
Authors: He H , Zhao Z-H , Han F-S , Liu X-H , Wang R , Zeng Y-J 
Published: January 2016

AbstractWe assessed the effects of protein kinase C ɛ (PKCɛ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKCɛ-overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKCɛ distribution and expression of principal proteins involved in PKCɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGFβ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKCɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGFβ, cTnI, vWF, SMA and factor VIII expression increased in animals with PKCɛ-overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKCɛ. Activation of PKCɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKCɛ expression may enhance the therapeutic effects of stem cell therapy for AMI.
Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer
Authors: Akimoto M , Hayashi J-I , Nakae S , Saito H , Takenaga K 
Published: January 2016

AbstractThe proinflammatory interleukin-33 (IL-33) binds to its receptor ST2L on the surface of immune cells and stimulates the production of Th2 cytokines; however, the effects of IL-33 on tumour cells are poorly understood. Here we show that ST2 was significantly downregulated in human lung cancer tissues and cells compared with normal lung tissues and cells. IL-33 expression was also inversely correlated with the stages of human lung cancers. In accordance with this finding, low-metastatic cells but not high-metastatic cells derived from Lewis lung carcinoma expressed functional ST2L. IL-33 was abundantly present in the tumours established by the low-metastatic cells compared with those formed by the high-metastatic cells. Although the low-metastatic cells scarcely expressed IL-33 in vitro, these cells did expry 6ess this molecule in vivo, likely due to stimulation by intratumoural IL-1β and IL-33. Importantly, IL-33 enhanced the cell death of ST2L-positive low-metastatic cells, but not of ST2L-negative high-metastatic cells, under glucose-depleted, glutamine-depleted and hypoxic conditions through p38 MAPK and mTOR activation, and in a mitochondria-dependent manner. The cell death was characterised by cytoplasmic blisters and karyolysis, which are unique morphological features of oncosis. Inevitably, the low-metastatic cells, but not of the high-metastatic cells, grew faster in IL-33−/− mice than in wild-type mice. Furthermore, IL-33 selected for the ST2L-positive, oncosis-resistant high-metastatic cells under conditions mimicking the tumour microenvironment. These data suggest that IL-33 enhances lung cancer progression by selecting for more malignant cells in the tumour microenvironment.
Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration
Authors: Detaille D , Vial G , Borel A-L , Cottet-Rouselle C , Hallakou-Bozec S , Bolze S , Fouqueray P , Fontaine E 
Published: January 2016

AbstractImeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of β-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert-butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death. These events were fully prevented by Imeglimin treatment. This protective effect on cell death occurred without any effect on oxygen consumption rate, on lactate production and on cytosolic redox or phosphate potentials. Imeglimin also dramatically decreased reactive oxygen species production, inhibiting specifically reverse electron transfer through complex I. We conclude that Imeglimin prevents hyperglycemia-induced cell death in HMEC-1 through inhibition of PTP opening without inhibiting mitochondrial respiration nor affecting cellular energy status. Considering the high prevalence of macrovascular and microvascular complications in type 2 diabetic subjects, these results together suggest a potential benefit of Imeglimin in diabetic angiopathy.
Strongly frustrated triangular spin lattice emerging from triplet dimer formation in honeycomb Li2IrO3
Authors: Nishimoto Satoshi , Katukuri Vamshi M. , Yushankhai Viktor , Stoll Hermann , Rößler Ulrich K. , Hozoi Liviu , Rousochatzakis Ioannis , van den Brink Jeroen 
Published: January 2016

AbstractIridium oxides with a honeycomb lattice have been identified as platforms for the much anticipated Kitaev topological spin liquid: the spin-orbit entangled states of Ir4+ in principle generate precisely the required type of anisotropic exchange. However, other magnetic couplings can drive the system away from the spin-liquid phase. With this in mind, here we disentangle the different magnetic interactions in Li2IrO3, a honeycomb iridate with two crystallographically inequivalent sets of adjacent Ir sites. Our ab initio many-body calculations show that, while both Heisenberg and Kitaev nearest-neighbour couplings are present, on one set of Ir–Ir bonds the former dominates, resulting in the formation of spin-triplet dimers. The triplet dimers frame a strongly frustrated triangular lattice and by exact cluster diagonalization we show that they remain protected in a wide region of the phase diagram.
Magnetoelectric effect and phase transitions in CuO in external magnetic fields
Authors: Wang Zhaosheng , Qureshi Navid , Yasin Shadi , Mukhin Alexander , Ressouche Eric , Zherlitsyn Sergei , Skourski Yurii , Geshev Julian , Ivanov Vsevolod , Gospodinov Marin , Skumryev Vassil 
Published: January 2016

AbstractApart from being so far the only known binary multiferroic compound, CuO has a much higher transition temperature into the multiferroic state, 230 K, than any other known material in which the electric polarization is induced by spontaneous magnetic order, typically lower than 100 K. Although the magnetically induced ferroelectricity of CuO is firmly established, no magnetoelectric effect has been observed so far as direct crosstalk between bulk magnetization and electric polarization counterparts. Here we demonstrate that high magnetic fields of ≈50 T are able to suppress the helical modulation of the spins in the multiferroic phase and dramatically affect the electric polarization. Furthermore, just below the spontaneous transition from commensurate (paraelectric) to incommensurate (ferroelectric) structures at 213 K, even modest magnetic fields induce a transition into the incommensurate structure and then suppress it at higher field. Thus, remarkable hidden magnetoelectric features are uncovered, establishing CuO as prototype multiferroic with abundance of competitive magnetic interactions.
Dynamic detection of electron spin accumulation in ferromagnet–semiconductor devices by ferromagnetic resonance
Authors: Liu Changjiang , Patel Sahil J. , Peterson Timothy A. , Geppert Chad C. , Christie Kevin D. , Stecklein Gordon , Palmstrøm Chris J. , Crowell Paul A. 
Published: January 2016

AbstractA distinguishing feature of spin accumulation in ferromagnet–semiconductor devices is its precession in a magnetic field. This is the basis for detection techniques such as the Hanle effect, but these approaches become ineffective as the spin lifetime in the semiconductor decreases. For this reason, no electrical Hanle measurement has been demonstrated in GaAs at room temperature. We show here that by forcing the magnetization in the ferromagnet to precess at resonance instead of relying only on the Larmor precession of the spin accumulation in the semiconductor, an electrically generated spin accumulation can be detected up to 300 K. The injection bias and temperature dependence of the measured spin signal agree with those obtained using traditional methods. We further show that this approach enables a measurement of short spin lifetimes (<100 ps), a regime that is not accessible in semiconductors using traditional Hanle techniques.
Insertion compounds and composites made by ball milling for advanced sodium-ion batteries
Authors: Zhang Biao , Dugas Romain , Rousse Gwenaelle , Rozier Patrick , Abakumov Artem M. , Tarascon Jean-Marie 
Published: January 2016

AbstractSodium-ion batteries have been considered as potential candidates for stationary energy storage because of the low cost and wide availability of Na sources. However, their future commercialization depends critically on control over the solid electrolyte interface formation, as well as the degree of sodiation at the positive electrode. Here we report an easily scalable ball milling approach, which relies on the use of metallic sodium, to prepare a variety of sodium-based alloys, insertion layered oxides and polyanionic compounds having sodium in excess such as the Na4V2(PO4)2F3 phase. The practical benefits of preparing sodium-enriched positive electrodes as reservoirs to compensate for sodium loss during solid electrolyte interphase formation are demonstrated by assembling full C/P′2-Na1[Fe0.5Mn0.5]O2 and C/‘Na3+xV2(PO4)2F3’ sodium-ion cells that show substantial increases (>10%) in energy storage density. Our findings may offer electrode design principles for accelerating the development of the sodium-ion technology.
A better-ventilated ocean triggered by Late Cretaceous changes in continental configuration
Authors: Donnadieu Yannick , Pucéat Emmanuelle , Moiroud Mathieu , Guillocheau François , Deconinck Jean- François 
Published: January 2016

AbstractOceanic anoxic events (OAEs) are large-scale events of oxygen depletion in the deep ocean that happened during pre-Cenozoic periods of extreme warmth. Here, to assess the role of major continental configuration changes occurring during the Late Cretaceous on oceanic circulation modes, which in turn influence the oxygenation level of the deep ocean, we use a coupled ocean atmosphere climate model. We simulate ocean dynamics during two different time slices and compare these with existing neodymium isotope data (ɛNd). Although deep-water production in the North Pacific is continuous, the simulations at 94 and 71 Ma show a shift in southern deep-water production sites from South Pacific to South Atlantic and Indian Ocean locations. Our modelling results support the hypothesis that an intensification of southern Atlantic deep-water production and a reversal of deep-water fluxes through the Caribbean Seaway were the main causes of the decrease in ɛNd values recorded in the Atlantic and Indian deep waters during the Late Cretaceous.
Visualizing band offsets and edge states in bilayer–monolayer transition metal dichalcogenides lateral heterojunction
Authors: Zhang Chendong , Chen Yuxuan , Huang Jing-Kai , Wu Xianxin , Li Lain-Jong , Yao Wang , Tersoff Jerry , Shih Chih-Kang 
Published: January 2016

AbstractSemiconductor heterostructures are fundamental building blocks for many important device applications. The emergence of two-dimensional semiconductors opens up a new realm for creating heterostructures. As the bandgaps of transition metal dichalcogenides thin films have sensitive layer dependence, it is natural to create lateral heterojunctions (HJs) using the same materials with different thicknesses. Here we show the real space image of electronic structures across the bilayer–monolayer interface in MoSe2 and WSe2, using scanning tunnelling microscopy and spectroscopy. Most bilayer–monolayer HJs are found to have a zig-zag-orientated interface, and the band alignment of such atomically sharp HJs is of type-I with a well-defined interface mode that acts as a narrower-gap quantum wire. The ability to utilize such commonly existing thickness terraces as lateral HJs is a crucial addition to the tool set for device applications based on atomically thin transition metal dichalcogenides, with the advantage of easy and flexible implementation.
Evidence for an ice shelf covering the central Arctic Ocean during the penultimate glaciation
Authors: Jakobsson Martin , Nilsson Johan , Anderson Leif , Backman Jan , Björk Göran , Cronin Thomas M. , Kirchner Nina , Koshurnikov Andrey , Mayer Larry , Noormets Riko , O’Regan Matthew , Stranne Christian , Ananiev Roman , Barrientos Macho Natalia , Cherniykh Denis , Coxall Helen , Eriksson Björn , Flodén Tom , Gemery Laura , Gustafsson Örjan , Jerram Kevin , Johansson Carina , Khortov Alexey , Mohammad Rezwan , Semiletov Igor 
Published: January 2016

AbstractThe hypothesis of a km-thick ice shelf covering the entire Arctic Ocean during peak glacial conditions was proposed nearly half a century ago. Floating ice shelves preserve few direct traces after their disappearance, making reconstructions difficult. Seafloor imprints of ice shelves should, however, exist where ice grounded along their flow paths. Here we present new evidence of ice-shelf groundings on bathymetric highs in the central Arctic Ocean, resurrecting the concept of an ice shelf extending over the entire central Arctic Ocean during at least one previous ice age. New and previously mapped glacial landforms together reveal flow of a spatially coherent, in some regions >1-km thick, central Arctic Ocean ice shelf dated to marine isotope stage 6 (∼140 ka). Bathymetric highs were likely critical in the ice-shelf development by acting as pinning points where stabilizing ice rises formed, thereby providing sufficient back stress to allow ice shelf thickening.
A role for Separase in telomere protection
Authors: Cipressa Francesca , Morciano Patrizia , Bosso Giuseppe , Mannini Linda , Galati Alessandra , Daniela Raffa Grazia , Cacchione Stefano , Musio Antonio , Cenci Giovanni 
Published: January 2016

AbstractDrosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity and are assembled independently of the sequence. Fly telomeres are protected by the terminin complex that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. We show that mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions (TFs), suggesting a role for Sse in telomere capping. We demonstrate that Separase binds terminin proteins and HP1, and that it is enriched at telomeres. Furthermore, we show that loss of Sse strongly reduces HP1 levels, and that HP1 overexpression in Sse mutants suppresses TFs, suggesting that TFs are caused by a HP1 diminution. Finally, we find that siRNA-induced depletion of ESPL1, the Sse human orthologue, causes telomere dysfunction and HP1 level reduction in primary fibroblasts, highlighting a conserved role of Separase in telomere protection.
Uncoupling of EGFR–RAS signaling and nuclear localization of YBX1 in colorectal cancer
Authors: Roßner F , Gieseler C , Morkel M , Royer H-D , Rivera M , Bläker H , Dietel M , Schäfer R , Sers C 
Published: January 2016

AbstractThe transcription factor YBX1 can act as a mediator of signals transmitted via the EGFR–RAS–MAPK axis. YBX1 expression has been associated with tumor progression and prognosis in multiple types of cancer. Immunohistochemical studies have revealed dependency between YBX1 expression and individual EGFR family members. We analyzed YBX1 and EGFR family proteins in a colorectal cancer (CRC) cohort and provide functional analyses of YBX1 in the context of EGFR–RAS–MAPK signaling. Immunohistochemistry for YBX1 and EGFR family receptors with two antibodies for YBX1 and EGFR were performed and related to clinicopathological data. We employed Caco2 cells expressing an inducible KRASV12 gene to determine effects on localization and levels of YBX1. Mouse xenografts of Caco2-KRASV12 cells were used to determine YBX1 dynamics in a tissue context. The two different antibodies against YBX1 showed discordant immunohistochemical stainings in cell culture and clinical specimens. Expression of YBX1 and EGFR family members were not correlated in CRC. Analysis of Caco2 xenografts displayed again heterogeneity of YBX1 staining with both antibodies. Our results suggest that YBX1 is controlled via complex regulatory mechanisms involving tumor stroma interaction and signal transduction processes. Our study highlights that YBX1 antibodies have different specificities, advocating their use in a combined manner.