bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined effects of FH (E404D) and ACOX2 (R409H) cause metabolic defects in primary cardiac malignant tumor
Authors: Zhou Xiangyu , Xu Mengjia , Zeng Weijia , Chen Zhongzhong , Lu Guohui , Gong Yun , Finnell Richard H. , Xiao Huasheng , Qiao Bin , Wang Hongyan 
Published: July 2018

AbstractPrimary malignant cardiac tumors (PMCTs) are extremely rare. The apparent immunity of the heart to invasive cancer has attracted considerable interest given the continuously rising incidence of cancer in other organs. This study aims to determine the conditions that could result in cardiac carcinoma and expand our understanding of cardiac tumor occurrence. We report two cases: a male (Patient-1) with primary cardiac malignant fibrous histiocytoma (MFH) and a female (Patient-2) with primary cardiac angiosarcoma. Merged genome-wide analyses of aCGH, Exome sequencing, and RNA-sequencing were performed on Patient-1 using peripheral blood, carcinoma tissue, and samples of adjacent normal tissue. Only whole-transcriptome analysis was carried out on Patient-2, due to insufficient quantities of sample from Patient-2. We identified a novel inherited loss of functional mutation of FH (Glu404Asp), a recurrent somatic hotspot mutation of PIK3CA (His1047Arg) and a somatic duplication in copy number of HIF1A. FH (E404D) severely compromised FH enzyme activity and lead to decreased protein expression in cardiac tumor tissues. We previously reported a functional mutation ACOX2 (R409H), which is potentially associated with decreased β-oxidation of fatty acids in the cardiac tumor tissue. Results of transcriptome analyses on two patients further revealed that the RNA expression of genes in the TCA cycle and beta-oxidation were uniformly downregulated. In this study, combined effects of FH (E404D) and ACOX2 (R409H) on metabolic switch from fatty acids to glucose were remarkably distinct, which might be an essential precondition to trigger the occurrence of PMCTs and mimic the Warburg effect, a hallmark of cancer metabolism.
Lipid droplet and peroxisome biogenesis occur at the same ER subdomains
Authors: Joshi Amit S. , Nebenfuehr Benjamin , Choudhary Vineet , Satpute-Krishnan Prasanna , Levine Tim P. , Golden Andy , Prinz William A. 
Published: July 2018

AbstractNascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined. We previously identified ER domains in S. cerevisiae containing the reticulon homology domain (RHD) protein Pex30 that are regions where preperoxisomal vesicles (PPVs) form. Here, we show that Pex30 domains are also sites where most nascent LDs form. Mature LDs usually remain associated with Pex30 subdomains, and the same Pex30 subdomain can simultaneously associate with a LD and a PPV or peroxisome. We find that in higher eukaryotes multiple C2 domain containing transmembrane protein (MCTP2) is similar to Pex30: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. Together, these findings indicate that most LDs and PPVs form and remain associated with conserved ER subdomains, and suggest a link between LD and peroxisome biogenesis.
Coherent deglacial changes in western Atlantic Ocean circulation
Authors: Ng Hong Chin , Robinson Laura F. , McManus Jerry F. , Mohamed Kais J. , Jacobel Allison W. , Ivanovic Ruza F. , Gregoire Lauren J. , Chen Tianyu 
Published: July 2018

AbstractAbrupt climate changes in the past have been attributed to variations in Atlantic Meridional Overturning Circulation (AMOC) strength. However, the exact timing and magnitude of past AMOC shifts remain elusive, which continues to limit our understanding of the driving mechanisms of such climate variability. Here we show a consistent signal of the 231Pa/230Th proxy that reveals a spatially coherent picture of western Atlantic circulation changes over the last deglaciation, during abrupt millennial-scale climate transitions. At the onset of deglaciation, we observe an early slowdown of circulation in the western Atlantic from around 19 to 16.5 thousand years ago (ka), consistent with the timing of accelerated Eurasian ice melting. The subsequent weakened AMOC state persists for over a millennium (~16.5–15 ka), during which time there is substantial ice rafting from the Laurentide ice sheet. This timing indicates a role for melting ice in driving a two-step AMOC slowdown, with a positive feedback sustaining continued iceberg calving and climate change during Heinrich Stadial 1.
Land-use emissions play a critical role in land-based mitigation for Paris climate targets
Authors: Harper Anna B. , Powell Tom , Cox Peter M. , House Joanna , Huntingford Chris , Lenton Timothy M. , Sitch Stephen , Burke Eleanor , Chadburn Sarah E. , Collins William J. , Comyn-Platt Edward , Daioglou Vassilis , Doelman Jonathan C. , Hayman Garry , Robertson Eddy , van Vuuren Detlef , Wiltshire Andy , Webber Christopher P. , Bastos Ana , Boysen Lena , Ciais Philippe , Devaraju Narayanappa , Jain Atul K. , Krause Andreas , Poulter Ben , Shu Shijie 
Published: July 2018

AbstractScenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO2) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO2 removal strategies. Here we show that additional land-use change to meet a 1.5 °C climate change target could result in net losses of carbon from the land. The effectiveness of BECCS strongly depends on several assumptions related to the choice of biomass, the fate of initial above ground biomass, and the fossil-fuel emissions offset in the energy system. Depending on these factors, carbon removed from the atmosphere through BECCS could easily be offset by losses due to land-use change. If BECCS involves replacing high-carbon content ecosystems with crops, then forest-based mitigation could be more efficient for atmospheric CO2 removal than BECCS.
A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma
Authors: Chen Xiaoyue , Zhang Minjie , Gan Haiyun , Wang Heping , Lee Jeong-Heon , Fang Dong , Kitange Gaspar J. , He Lihong , Hu Zeng , Parney Ian F. , Meyer Fredric B. , Giannini Caterina , Sarkaria Jann N. , Zhang Zhiguo 
Published: July 2018

AbstractTemozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Here we report that an enhancer, located between the promoters of marker of proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. We show that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation.
Precoce and opposite response of proteasome activity after acute or chronic exposure of C. elegans to γ-radiation
Authors: Dubois Cécile , Lecomte Catherine , Ruys Sébastien Pyr dit , Kuzmic Mira , Della-Vedova Claire , Dubourg Nicolas , Galas Simon , Frelon Sandrine 
Published: July 2018

AbstractSpecies are chronically exposed to ionizing radiation, a natural phenomenon which can be enhanced by human activities. The induced toxicity mechanisms still remain unclear and seem depending on the mode of exposure, i.e. acute and chronic. To better understand these phenomena, studies need to be conducted both at the subcellular and individual levels. Proteins, functional molecules in organisms, are the targets of oxidative damage (especially via their carbonylation (PC)) and are likely to be relevant biomarkers. After exposure of Caenorhabditis elegans to either chronic or acute γ rays we showed that hatching success is impacted after acute but not after chronic irradiation. At the molecular level, the carbonylated protein level in relation with dose was slightly different between acute and chronic exposure whereas the proteolytic activity is drastically modified. Indeed, whereas the 20S proteasome activity is inhibited by acute irradiation from 0.5 Gy, it is activated after chronic irradiation from 1 Gy. As expected, the 20S proteasome activity is mainly modified by irradiation whereas the 26S and 30S activity are less changed. This study provides preliminaries clues to understand the role of protein oxidation and proteolytic activity in the radiation-induced molecular mechanisms after chronic versus acute irradiation in C. elegans.
Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response
Authors: Shen Chwan-Li , Kaur Gurvinder , Wanders Desiree , Sharma Shaligram , Tomison Michael D. , Ramalingam Latha , Chung Eunhee , Moustaid-Moussa Naima , Mo Huanbiao , Dufour Jannette M. 
Published: July 2018

AbstractDiabetes is a risk factor for osteoporosis. Annatto-extracted tocotrienols (TT) have proven benefits in preserving bone matrix. Here, we evaluated the effects of dietary TT on glucose homeostasis, bone properties, and liver pro-inflammatory mRNA expression in high-fat diet (HFD)-induced type 2 diabetic (T2DM) mice. 58 male C57BL/6 J mice were divided into 5 groups: low-fat diet (LFD), HFD, HFD + 400 mgTT/kg diet (T400), HFD + 1600 mgTT/kg diet (T1600), and HFD + 200 mg metformin/kg (Met) for 14 weeks. Relative to the HFD group, both TT-supplemented groups (1) improved glucose homeostasis by lowering the area under the curve for both glucose tolerance and insulin tolerance tests, (2) increased serum procollagen I intact N-terminal propeptide (bone formation) level, trabecular bone volume/total volume, trabecular number, connectivity density, and cortical thickness, (3) decreased collagen type 1 cross-linked C-telopeptide (bone resorption) levels, trabecular separation, and structure model index, and (4) suppressed liver mRNA levels of inflammation markers including IL-2, IL-23, IFN-γ, MCP-1, TNF-α, ITGAX and F4/80. There were no differences in glucose homeostasis and liver mRNA expression among T400, T1600, and Met. The order of osteo-protective effects was LFD ≥T1600 ≥T400 = Met >HFD. Collectively, these data suggest that TT exerts osteo-protective effects in T2DM mice by regulating glucose homeostasis and suppressing inflammation.
Greenland ice mass loss during the Younger Dryas driven by Atlantic Meridional Overturning Circulation feedbacks
Authors: Rainsley Eleanor , Menviel Laurie , Fogwill Christopher J. , Turney Chris S. M. , Hughes Anna L. C. , Rood Dylan H. 
Published: July 2018

AbstractUnderstanding feedbacks between the Greenland Ice Sheet (GrIS) and the Atlantic Meridional Overturning Circulation (AMOC) is crucial for reducing uncertainties over future sea level and ocean circulation change. Reconstructing past GrIS dynamics can extend the observational record and elucidate mechanisms that operate on multi-decadal timescales. We report a highly-constrained last glacial vertical profile of cosmogenic isotope exposure ages from Sermilik Fjord, a marine-terminating ice stream in the southeast sector of the GrIS. Our reconstruction reveals substantial ice-mass loss throughout the Younger Dryas (12.9-11.7 ka), a period of marked atmospheric and sea-surface cooling. Earth-system modelling reveals that southern GrIS marginal melt was likely driven by strengthening of the Irminger Current at depth due to a weakening of the AMOC during the Younger Dryas. This change in North Atlantic circulation appears to have drawn warm subsurface waters to southeast Greenland despite markedly cooler sea surface temperatures, enhancing thermal erosion at the grounding lines of palaeo ice-streams, supporting interpretation of regional marine-sediment cores. Given current rates of GrIS meltwater input into the North Atlantic and the vulnerability of major ice streams to water temperature changes at the grounding line, this mechanism has important implications for future AMOC changes and northern hemisphere heat transport.
Ocean acidification drives community shifts towards simplified non-calcified habitats in a subtropical−temperate transition zone
Authors: Agostini Sylvain , Harvey Ben P. , Wada Shigeki , Kon Koetsu , Milazzo Marco , Inaba Kazuo , Hall-Spencer Jason M. 
Published: July 2018

AbstractRising atmospheric concentrations of carbon dioxide are causing surface seawater pH and carbonate ion concentrations to fall in a process known as ocean acidification. To assess the likely ecological effects of ocean acidification we compared intertidal and subtidal marine communities at increasing levels of pCO2 at recently discovered volcanic seeps off the Pacific coast of Japan (34° N). This study region is of particular interest for ocean acidification research as it has naturally low levels of surface seawater pCO2 (280–320 µatm) and is located at a transition zone between temperate and sub-tropical communities. We provide the first assessment of ocean acidification effects at a biogeographic boundary. Marine communities exposed to mean levels of pCO2 predicted by 2050 experienced periods of low aragonite saturation and high dissolved inorganic carbon. These two factors combined to cause marked community shifts and a major decline in biodiversity, including the loss of key habitat-forming species, with even more extreme community changes expected by 2100. Our results provide empirical evidence that near-future levels of pCO2 shift sub-tropical ecosystems from carbonate to fleshy algal dominated systems, accompanied by biodiversity loss and major simplification of the ecosystem.
Blast exposure elicits blood-brain barrier disruption and repair mediated by tight junction integrity and nitric oxide dependent processes
Authors: Logsdon Aric F. , Meabon James S. , Cline Marcella M. , Bullock Kristin M. , Raskind Murray A. , Peskind Elaine R. , Banks William A. , Cook David G. 
Published: July 2018

AbstractMild blast-induced traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption. However, the mechanisms whereby blast disrupts BBB integrity are not well understood. To address this issue BBB permeability to peripherally injected 14C-sucrose and 99mTc-albumin was quantified in ten brain regions at time points ranging from 0.25 to 72 hours. In mice, repetitive (2X) blast provoked BBB permeability to 14C-sucrose that persisted in specific brain regions from 0.25 to 72 hours. However, 99mTc-albumin revealed biphasic BBB disruption (open-closed-open) over the same interval, which was most pronounced in frontal cortex and hippocampus. This indicates that blast initiates interacting BBB disruption and reparative processes in specific brain regions. Further investigation of delayed (72 hour) BBB disruption revealed that claudin-5 (CLD5) expression was disrupted specifically in the hippocampus, but not in dorsal striatum, a brain region that showed no blast-induced BBB permeability to sucrose or albumin. In addition, we found that delayed BBB permeability and disrupted CLD5 expression were blocked by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). These data argue that latent nitric oxide-dependent signaling pathways initiate processes that result in delayed BBB disruption, which are manifested in a brain-region specific manner.
Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression
Authors: Cho Sungrae , Chae Jin Sung , Shin Hocheol , Shin Yujeong , Song Haeun , Kim Youngwook , Yoo Byong Chul , Roh Kangsan , Cho Seungchan , Kil Eui-joon , Byun Hee-seong , Cho Sang-ho , Park Seyeon , Lee Sukchan , Yeom Chang-Hwan 
Published: July 2018

AbstractL-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-ascorbic acid. In this study, we demonstrate that L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.
Validating Antibodies for Quantitative Western Blot Measurements with Microwestern Array
Authors: Koch Rick J. , Barrette Anne Marie , Stern Alan D. , Hu Bin , Bouhaddou Mehdi , Azeloglu Evren U. , Iyengar Ravi , Birtwistle Marc R. 
Published: July 2018

AbstractFluorescence-based western blots are quantitative in principal, but require determining linear range for each antibody. Here, we use microwestern array to rapidly evaluate suitable conditions for quantitative western blotting, with up to 192 antibody/dilution/replicate combinations on a single standard size gel with a seven-point, two-fold lysate dilution series (~100-fold range). Pilot experiments demonstrate a high proportion of investigated antibodies (17/24) are suitable for quantitative use; however this sample of antibodies is not yet comprehensive across companies, molecular weights, and other important antibody properties, so the ubiquity of this property cannot yet be determined. In some cases microwestern struggled with higher molecular weight membrane proteins, so the technique may not be uniformly applicable to all validation tasks. Linear range for all validated antibodies is at least 8-fold, and up to two orders of magnitude. Phospho-specific and total antibodies do not have discernable trend differences in linear range or limit of detection. Total antibodies generally required higher working concentrations, but more comprehensive antibody panels are required to better establish whether this trend is general or not. Importantly, we demonstrate that results from microwestern analyses scale to normal “macro” western for a subset of antibodies.
Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models
Authors: Tegge Allison N. , Rodrigues Richard R. , Larkin Adam L. , Vu Lucas , Murali T. M. , Rajagopalan Padmavathy 
Published: July 2018

AbstractLiver homeostasis requires the presence of both parenchymal and non-parenchymal cells (NPCs). However, systems biology studies of the liver have primarily focused on hepatocytes. Using an organotypic three-dimensional (3D) hepatic culture, we report the first transcriptomic study of liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) cultured with hepatocytes. Through computational pathway and interaction network analyses, we demonstrate that hepatocytes, LSECs and KCs have distinct expression profiles and functional characteristics. Our results show that LSECs in the presence of KCs exhibit decreased expression of focal adhesion kinase (FAK) signaling, a pathway linked to LSEC dedifferentiation. We report the novel result that peroxisome proliferator-activated receptor alpha (PPARα) is transcribed in LSECs. The expression of downstream processes corroborates active PPARα signaling in LSECs. We uncover transcriptional evidence in LSECs for a feedback mechanism between PPARα and farnesoid X-activated receptor (FXR) that maintains bile acid homeostasis; previously, this feedback was known occur only in HepG2 cells. We demonstrate that KCs in 3D liver models display expression patterns consistent with an anti-inflammatory phenotype when compared to monocultures. These results highlight the distinct roles of LSECs and KCs in maintaining liver function and emphasize the need for additional mechanistic studies of NPCs in addition to hepatocytes in liver-mimetic microenvironments.
Electronic contribution in heat transfer at metal-semiconductor and metal silicide-semiconductor interfaces
Authors: Hamaoui Georges , Horny Nicolas , Hua Zilong , Zhu Tianqi , Robillard Jean-François , Fleming Austin , Ban Heng , Chirtoc Mihai 
Published: July 2018

AbstractThis work presents a direct measurement of the Kapitza thermal boundary resistance Rth, between platinum-silicon and platinum silicide-silicon interfaces. Experimental measurements were made using a frequency domain photothermal radiometry set up at room temperature. The studied samples consist of ≈50 nm of platinum and ≈110 nm of platinum silicide on silicon substrates with different doping levels. The substrate thermal diffusivity was found via a hybrid frequency/spatial domain thermoreflectance set up. The films and the interfaces between the two layers were characterized using scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray spectroscopy. X-ray diffraction was also used to determine the atomic and molecular structures of the samples. The results display an effect of the annealing process on the Kapitza resistance and on the thermal diffusivities of the coatings, related to material and interface changes. The influence of the substrate doping levels on the Kapitza resistance is studied to check the correlation between the Schottky barrier and the interfacial heat conduction. It is suggested that the presence of charge carriers in silicon may create new channels for heat conduction at the interface, with an efficiency depending on the difference between the metal’s and substrate’s work functions.