bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geniposide promotes beta-cell regeneration and survival through regulating β-catenin/TCF7L2 pathway
Authors: Yao D D , Yang L , Wang Y , Liu C , Wei Y J , Jia X B , Yin W , Shu L 
Published: May 2015

AbstractT-cell factor 7-like 2 (TCF7L2) is an important transcription factor of Wnt/β-catenin signaling, which has critical roles in β-cell survival and regeneration. In preliminary screening assay, we found geniposide, a naturally occurring compound, was able to increase TCF7L2 mRNA level in Min6 cells. Here we aimed to investigate the role of geniposide in β-cell and underlying mechanism involved. Geniposide was found to promote β-cell survival by increasing β-cell proliferation and decreasing β-cell apoptosis in cultured mouse islets after challenge with diabetic stimuli. Geniposide protected β-cell through activating Wnt signaling, enhanced expressions of TCF7L2 and GLP-1R, activated AKT, inhibited GSK3β activity, and promoted β-catenin nuclear translocation. The protective effect of geniposide was remarkably suppressed by siRNAs against β-catenin, or by ICG001 (β-catenin/TCF-mediated transcription inhibitor). Moreover, geniposide promoted β-cell regeneration in vivo to normalize blood glucose in high-fat diet and db/db mice. Increased β-cell proliferation was observed in pancreatic sections of geniposide-treated diabetic mice. Most importantly, geniposide triggered small islet-like cell clusters formation as a result of β-cell neogenesis from ductal epithelium, which was well correlated with the increase in TCF7L2 expression. In exocrine cells isolated from mouse pancreas, geniposide could induce duct cell differentiation through upregulating TCF7L2 expression and activating JAK2/STAT3 pathway. Taken together, we identified a novel role of geniposide in promoting β-cell survival and regeneration by mechanisms involving the activation of β-catenin/TCF7L2 signaling. Our finding highlights the potential value of geniposide as a possible treatment for type 2 diabetes.
Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation
Authors: Kluckova K , Sticha M , Cerny J , Mracek T , Dong L , Drahota Z , Gottlieb E , Neuzil J , Rohlena J 
Published: May 2015

AbstractRespiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate the role of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining the Qpsite by site-directed mutagenesis. Cell lines carrying these mutations were characterized on the bases of CII activity and exposed to Qpsite inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC variants, which support succinate-mediated respiration and maintain low intracellular succinate, were less efficiently inhibited by MitoVES than the wild-type (WT) variant. Importantly, associated ROS generation and cell death induction was also impaired, and cell death in the WT cells was malonate and catalase sensitive. In contrast, the S68A variant was much more susceptible to TTFA inhibition than the I56F variant or the WT CII, which was again reflected by enhanced ROS formation and increased malonate- and catalase-sensitive cell death induction. The R72C variant that accumulates intracellular succinate due to compromised CII activity was resistant to MitoVES and TTFA treatment and did not increase ROS, even though TTFA efficiently generated ROS at low succinate in mitochondria isolated from R72C cells. Similarly, the high-affinity Qpsite inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated succinate only moderately. These results demonstrate that cell death initiation upon CII inhibition depends on ROS and that the extent of cell death correlates with the potency of inhibition at the Qpsite unless intracellular succinate is high. In addition, this validates the Qpsite of CII as a target for cell death induction with relevance to cancer therapy.
PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy
Authors: Wang S-C , Li Y-H , Piao H-L , Hong X-W , Zhang D , Xu Y-Y , Tao Y , Wang Y , Yuan M-M , Li D-J , Du M-R 
Published: May 2015

AbstractCD8+ T cells are critical in the balance between fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T cells from decidua greatly outnumbered those from peripheral blood during human early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+ and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co-expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in decidua. This population exhibited high proliferative activity and Th2-type cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in vitro proliferation and Th2-type cytokine production while increased trophoblast killing and IFN-γ producing capacities of CD8+ T cells. Pregnant CBA/J females challenged with Tim-3 and/or PD-1 blocking antibodies were more susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction. Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were significantly impaired in miscarriage. These findings underline the important roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and maintaining normal pregnancy.
Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells
Authors: Meganathan K , Jagtap S , Srinivasan S P , Wagh V , Hescheler J , Hengstler J , Leist M , Sachinidis A 
Published: May 2015

AbstractHuman embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling. Analysis of the gene expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2, ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A, DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378 increases the expression of OTX2 and EMX2, which supports our hypothesis that HDACi targets forebrain markers through miR-378. In conclusion, multilineage differentiation in vitro test system is very sensitive for monitoring molecular activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378 seems to repress the expression of the OTX2 and EMX2 and therefore could be a regulator of the development of neural tube and dorsal forebrain neurons.
Podocyte apoptosis is prevented by blocking the Toll-like receptor pathway
Authors: Saurus P , Kuusela S , Lehtonen E , Hyvönen M E , Ristola M , Fogarty C L , Tienari J , Lassenius M I , Forsblom C , Lehto M , Saleem M A , Groop P-H , Holthöfer H , Lehtonen S 
Published: May 2015

AbstractHigh serum lipopolysaccharide (LPS) activity in normoalbuminuric patients with type 1 diabetes (T1D) predicts the progression of diabetic nephropathy (DN), but the mechanisms behind this remain unclear. We observed that treatment of cultured human podocytes with sera from normoalbuminuric T1D patients with high LPS activity downregulated 3-phosphoinositide-dependent kinase-1 (PDK1), an activator of the Akt cell survival pathway, and induced apoptosis. Knockdown of PDK1 in cultured human podocytes inhibited antiapoptotic Akt pathway, stimulated proapoptotic p38 MAPK pathway, and increased apoptosis demonstrating an antiapoptotic role for PDK1 in podocytes. Interestingly, PDK1 was downregulated in the glomeruli of diabetic rats and patients with type 2 diabetes before the onset of proteinuria, further suggesting that reduced expression of PDK1 associates with podocyte injury and development of DN. Treatment of podocytes in vitro and mice in vivo with LPS reduced PDK1 expression and induced apoptosis, which were prevented by inhibiting the Toll-like receptor (TLR) signaling pathway with the immunomodulatory agent GIT27. Our data show that LPS downregulates the cell survival factor PDK1 and induces podocyte apoptosis, and that blocking the TLR pathway with GIT27 may provide a non-nephrotoxic means to prevent the progression of DN.
Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury
Authors: Deutsch M , Graffeo C S , Rokosh R , Pansari M , Ochi A , Levie E M , Van Heerden E , Tippens D M , Greco S , Barilla R , Tomkötter L , Zambirinis C P , Avanzi N , Gulati R , Pachter H L , Torres-Hernandez A , Eisenthal A , Daley D , Miller G 
Published: May 2015

AbstractNecroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately.
Stochasticity, periodicity and localized light structures in partially mode-locked fibre lasers
Authors: Churkin D. V. , Sugavanam S. , Tarasov N. , Khorev S. , Smirnov S. V. , Kobtsev S. M. , Turitsyn S. K. 
Published: May 2015

AbstractPhysical systems with co-existence and interplay of processes featuring distinct spatio-temporal scales are found in various research areas ranging from studies of brain activity to astrophysics. The complexity of such systems makes their theoretical and experimental analysis technically and conceptually challenging. Here, we discovered that while radiation of partially mode-locked fibre lasers is stochastic and intermittent on a short time scale, it exhibits non-trivial periodicity and long-scale correlations over slow evolution from one round-trip to another. A new technique for evolution mapping of intensity autocorrelation function has enabled us to reveal a variety of localized spatio-temporal structures and to experimentally study their symbiotic co-existence with stochastic radiation. Real-time characterization of dynamical spatio-temporal regimes of laser operation is set to bring new insights into rich underlying nonlinear physics of practical active- and passive-cavity photonic systems.
JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis
Authors: Abe Yohei , Rozqie Royhan , Matsumura Yoshihiro , Kawamura Takeshi , Nakaki Ryo , Tsurutani Yuya , Tanimura-Inagaki Kyoko , Shiono Akira , Magoori Kenta , Nakamura Kanako , Ogi Shotaro , Kajimura Shingo , Kimura Hiroshi , Tanaka Toshiya , Fukami Kiyoko , Osborne Timothy F. , Kodama Tatsuhiko , Aburatani Hiroyuki , Inagaki Takeshi , Sakai Juro 
Published: May 2015

AbstractHistone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the β1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound PPARγ. This complex confers β-adrenergic-induced rapid JMJD1A recruitment to target sites and facilitates long-range chromatin interactions and target gene activation. This rapid gene induction is dependent on S265 phosphorylation but not on demethylation activity. Our results show that JMJD1A has two important roles in regulating hormone-stimulated chromatin dynamics that modulate thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and functions as a cAMP-responsive scaffold that facilitates long-range chromatin interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation.
Competition between recombination and extraction of free charges determines the fill factor of organic solar cells
Authors: Bartesaghi Davide , Pérez Irene del Carmen , Kniepert Juliane , Roland Steffen , Turbiez Mathieu , Neher Dieter , Koster L. Jan Anton 
Published: May 2015

AbstractAmong the parameters that characterize a solar cell and define its power-conversion efficiency, the fill factor is the least well understood, making targeted improvements difficult. Here we quantify the competition between charge extraction and recombination by using a single parameter θ, and we demonstrate that this parameter is directly related to the fill factor of many different bulk-heterojunction solar cells. Our finding is supported by experimental measurements on 15 different donor:acceptor combinations, as well as by drift-diffusion simulations of organic solar cells in which charge-carrier mobilities, recombination rate, light intensity, energy levels and active-layer thickness are all varied over wide ranges to reproduce typical experimental conditions. The results unify the fill factors of several very different donor:acceptor combinations and give insight into why fill factors change so much with thickness, light intensity and materials properties. To achieve fill factors larger than 0.8 requires further improvements in charge transport while reducing recombination.
Thermally induced collision of droplets in an immiscible outer fluid
Authors: Davanlou Ashkan , Kumar Ranganathan 
Published: May 2015

AbstractMicro-total analysis systems (μTAS) have attracted wide attention and are identified as a promising solution for sample transport, filtration, chemical reactions, separation and detection. Despite their popularity, the selection of an appropriate mechanism for droplet transport and coalescence has always been a challenge. This paper investigates the use of Marangoni flow as a mechanism for levitating and transporting droplets on immiscible liquid films at higher speeds than is possible currently. For the first time, we show that it is possible to realize the natural coalescence of droplets through Marangoni effect without any external stimulation and deliver the coalesced droplet to a certain destination through the use of surface tension gradients. The effects of shape and size on collision outcome are studied. Regions of coalescence and stretching separation of colliding droplets are delineated based on Weber number and impact number. In addition, the effect of viscosity on post collision regimes is studied. The findings in this fundamental study can be beneficial to many applications such as welding, drug delivery and microfluidics devices in controlling small droplets and targeting them to various locations.
On granular elasticity
Authors: Sun Qicheng , Jin Feng , Wang Guangqian , Song Shixiong , Zhang Guohua 
Published: May 2015

AbstractMesoscopic structures form in dense granular materials due to the self-organisation of the constituent particles. These structures have internal structural degrees of freedom in addition to the translational degree of freedom. The resultant granular elasticity, which exhibits intrinsic variations and inevitable relaxation, is a key quantity that accounts for macroscopic solid- or fluid-like properties and the transitions between them. In this work, we propose a potential energy landscape (PEL) with local stable basins and low elastic energy barriers to analyse the nature of granular elasticity. A function for the elastic energy density is proposed for stable states and is further calibrated with ultrasonic measurements. Fluctuations in the elastic energy due to the evolution of internal structures are proposed to describe a so-called configuration temperature Tc as a counterpart of the classical kinetic granular temperature Tk that is attributed to the translational degrees of freedom. The two granular temperatures are chosen as the state variables and a fundamental equation is established to develop non-equilibrium thermodynamics for granular materials. Due to the relatively low elastic energy barrier in the PEL, granular elasticity relaxes more under common mechanical loadings and a simple model based on mean-field theory is developed to account for this behaviour.
Using “Tender” X-ray Ambient Pressure X-Ray Photoelectron Spectroscopy as A Direct Probe of Solid-Liquid Interface
Authors: Axnanda Stephanus , Crumlin Ethan J. , Mao Baohua , Rani Sana , Chang Rui , Karlsson Patrik G. , Edwards Mårten O. M. , Lundqvist Måns , Moberg Robert , Ross Phil , Hussain Zahid , Liu Zhi 
Published: May 2015

AbstractWe report a new method to probe the solid-liquid interface through the use of a thin liquid layer on a solid surface. An ambient pressure XPS (AP-XPS) endstation that is capable of detecting high kinetic energy photoelectrons (7 keV) at a pressure up to 110 Torr has been constructed and commissioned. Additionally, we have deployed a “dip & pull” method to create a stable nanometers-thick aqueous electrolyte on platinum working electrode surface. Combining the newly constructed AP-XPS system, “dip & pull” approach, with a “tender” X-ray synchrotron source (2 keV–7 keV), we are able to access the interface between liquid and solid dense phases with photoelectrons and directly probe important phenomena occurring at the narrow solid-liquid interface region in an electrochemical system. Using this approach, we have performed electrochemical oxidation of the Pt electrode at an oxygen evolution reaction (OER) potential. Under this potential, we observe the formation of both Pt2+ and Pt4+ interfacial species on the Pt working electrode in situ. We believe this thin-film approach and the use of “tender” AP-XPS highlighted in this study is an innovative new approach to probe this key solid-liquid interface region of electrochemistry.
A seed mixture increases dominance of resistance to Bt cotton in Helicoverpa zea
Authors: Brévault Thierry , Tabashnik Bruce E. , Carrière Yves 
Published: May 2015

AbstractWidely grown transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) can benefit agriculture, but adaptation by pests threatens their continued success. Refuges of host plants that do not make Bt toxins can promote survival of susceptible insects and delay evolution of resistance, particularly if resistance is inherited as a recessive trait. However, data have been lacking to compare the dominance of resistance when Bt and non-Bt seeds are planted in random mixtures versus separate blocks. Here we report results from greenhouse experiments with transgenic cotton producing Bt toxin Cry1Ac and the bollworm, Helicoverpa zea, showing that the dominance of resistance was significantly higher in a seed mixture relative to a block of Bt cotton. The proportion of larvae on non-Bt cotton plants in the seed mixture was also significantly higher than expected under the null hypothesis of random distribution. In simulations based on observed survival, resistance evolved 2- to 4.5-fold faster in the seed mixture relative to separate blocks of Bt and non-Bt cotton. These findings support previous modelling results indicating that block refuges may be more effective than seed mixtures for delaying resistance in pests with mobile larvae and inherently low susceptibility to the toxins in Bt crops.
Ca-Mediated Electroformation of Cell-Sized Lipid Vesicles
Authors: Tao Fei , Yang Peng 
Published: May 2015

AbstractCell-sized lipid giant unilamellar vesicles (GUVs) are formed when lipid molecules self-assemble to construct a single bilayer compartment with similar morphology to living cells. The physics of self-assembly process is only generally understood and the size distribution of GUVs tends to be very polydisperse. Herein we report a strategy for the production of controlled size distributions of GUVs by a novel mechanism dissecting the mediation ability of calcium (Ca) on the conventional electroformation of GUVs. We finely construct both of the calcium ion (Ca2+) and calcium carbonate (CaCO3) mineral adsorption layers on a lipid film surface respectively during the electroformation of GUVs. It is found that Ca2+Slip plane polarized by alternating electric field could induce a pattern of electroosmotic flow across the surface and thus confine the fusion and growth of GUVs to facilitate the formation of uniform GUVs. The model is further improved by directly using CaCO3that is in situ formed on a lipid film surface, providing a GUV population with narrow polydispersity. The two models deciphers the new biological function of calcium on the birth of cell-like lipid vesicles and thus might be potentially relevant to the construction of new model to elucidate the cellular development process.
Characterization of the thermolysis products of Nafion membrane: A potential source of perfluorinated compounds in the environment
Authors: Feng Mingbao , Qu Ruijuan , Wei Zhongbo , Wang Liansheng , Sun Ping , Wang Zunyao 
Published: May 2015

AbstractThe thermal decomposition of Nafion N117 membrane, a typical perfluorosulfonic acid membrane that is widely used in various chemical technologies, was investigated in this study. Structural identification of thermolysis products in water and methanol was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). The fluoride release was studied using an ion-chromatography system and the membrane thermal stability was characterized by thermogravimetric analysis. Notably, several types of perfluorinated compounds (PFCs) including perfluorocarboxylic acids were detected and identified. Based on these data, a thermolysis mechanism was proposed involving cleavage of both the polymer backbone and its side chains by attack of radical species. This is the first systematic report on the thermolysis products of Nafion by simulating its high-temperature operation and disposal process via incineration. The results of this study indicate that Nafion is a potential environmental source of PFCs, which have attracted growing interest and concern in recent years. Additionally, this study provides an analytical justification of the LC/ESI-MS/MS method for characterizing the degradation products of polymer electrolyte membranes. These identifications can substantially facilitate an understanding of their decomposition mechanisms and offer insight into the proper utilization and effective management on these membranes.