bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQQ209L-driven melanoma
Authors: Patel B R , Tall G G 
Published: June 2016

AbstractThe heterotrimeric G protein α subunit oncogenes GNAQ or GNA11 carry Q209X or R183X activating mutations and are present with ~90% frequency in human uveal melanomas. Forced expression of GNAQ/11Q209L in melanocytes is sufficient to drive metastatic melanoma in immune-compromised mice. No known drugs directly target these oncogenic G proteins. Ric-8A is the molecular chaperone that selectively folds Gαq/i/13 subunits. Targeting Ric-8A serves as a rational, yet unexplored approach to reduce the functional abundance of oncogenic Gαq/11 in order to blunt cancer signaling. Here, using mouse melanocyte cell graft tumorigenesis models, we determined that Ric-8A genetic ablation attenuated the abundance and melanoma-driving potential of Gαq-Q209L. A new conditional Ric-8AFlox/Flox; Rosa-CreER+/− mouse strain was derived and used as a tissue source to culture an immortalized, tamoxifen-inducible Ric-8A knockout melanocyte cell line that required 12-O-tetradecanoylphorbol-13-acetate (TPA, phorbol ester) for growth. The cell line failed to grow tumors when grafted into immune-compromised mice regardless of Ric-8A expression. Stable expression of human GNAQQ209L, but not GNAQWT in the cell line promoted TPA-independent cell proliferation, and upon cell grafting in mice, the initiation and robust growth of darkly-pigmented melanoma tumors. Deletion of Ric-8A in GNAQQ209L cells restored TPA-dependent growth, reduced Gαq-Q209L below detectable levels and completely mitigated tumorigenesis from primary or secondary cell line grafts. Interestingly, TPA treatment of cultured GNAQQ209L cells or host animals grafted with GNAQQ209L cells also sharply reduced Gαq-Q209L abundance and tumorigenic capacity. Finally, tumorigenesis initiated from GNAQQ209L cell grafts, followed by host mouse systemic tamoxifen treatment to delete Ric-8A in the grafted cells completely abrogated GNAQQ209L-driven tumor progression unless a stable human RIC-8A transgene was used to rescue the floxed Ric-8A alleles. Our work defines two new rational targets that may be developed as potential uveal melanoma therapies through reduction of Gαq/11-Q209L oncoprotein abundance: (1) Ric-8A inhibition and (2) phorbol ester treatment.
Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans
Authors: Czakai Kristin , Leonhardt Ines , Dix Andreas , Bonin Michael , Linde Joerg , Einsele Hermann , Kurzai Oliver , Loeffler Jürgen 
Published: June 2016

AbstractInvasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungiAspergillus fumigatusandCandida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted withA. fumigatus, C. albicansor LPS was performed andKrüppel-like factor 4 (KLF4)was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.
Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
Authors: Peng Xiaoxiao , Giménez-Cassina Alfredo , Petrus Paul , Conrad Marcus , Rydén Mikael , Arnér Elias S. J. 
Published: June 2016

AbstractRecently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txnrd1 (Txnrd1−/−) displayed increased metabolic flux, glycogen storage, lipogenesis and adipogenesis. This phenotype coincided with upregulated PPARγ expression, promotion of mitotic clonal expansion and downregulation of p27 and p53. Enhanced Akt activation also contributed to augmented adipogenesis and insulin sensitivity. Knockdown of TXNRD1 transcripts accelerated adipocyte differentiation also in human primary preadipocytes. Furthermore, TXNRD1 transcript levels in subcutaneous adipose tissue from 56 women were inversely associated with insulin sensitivity in vivo and lipogenesis in their isolated adipocytes. These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulation.
The Effects of Serum ANGPTL8/betatrophin on the Risk of Developing the Metabolic Syndrome – A Prospective Study
Authors: Wang Haoyu , Lai Yaxin , Han Cheng , Liu Aihua , Fan Chenling , Wang Hong , Zhang Hongmei , Ding Shuangning , Teng Weiping , Shan Zhongyan 
Published: June 2016

AbstractANGPTL8/betatrophin is a recently discovered hormone, which mainly synthesized and secreted by liver and adipose tissue, playing a critical role in pancreatic beta cell proliferation. Previous studies have suggested that serum ANGPTL8/betatrophin levels are associated with obesity and diabetes mellitus. Here, we evaluated the prospective association between ANGPTL8/betatrophin and the metabolic syndrome from a community-based cohort of 153 adults without metabolic syndrome. After 3.5-year follow-up, we observed an inverse correlation between the baseline ANGPTL8/betatrophin levels and the incidence of metabolic syndrome, even after multivariate adjustments. In receiver operating characteristic analysis, the area underneath the curve for ANGPTL8/betatrophin was 0.70 in males and 0.86 in females and the optimal cut-off values were 23.9 ng/mL and 31.1 ng/mL, respectively. This article suggests that ANGPTL8/betatrophin might be useful in predicting newly-onset metabolic syndrome and its progression in clinical setting.
Experimental Realization of a Reflections-Free Compact Delay Line Based on a Photonic Topological Insulator
Authors: Lai Kueifu , Ma Tsuhsuang , Bo Xiao , Anlage Steven , Shvets Gennady 
Published: June 2016

AbstractElectromagnetic (EM) waves propagating through an inhomogeneous medium are generally scattered whenever the medium’s electromagnetic properties change on the scale of a single wavelength. This fundamental phenomenon constrains how optical structures are designed and interfaced with each other. Recent theoretical work indicates that electromagnetic structures collectively known as photonic topological insulators (PTIs) can be employed to overcome this fundamental limitation, thereby paving the way for ultra-compact photonic structures that no longer have to be wavelength-scale smooth. Here we present the first experimental demonstration of a photonic delay line based on topologically protected surface electromagnetic waves (TPSWs) between two PTIs which are the EM counterparts of the quantum spin-Hall topological insulators in condensed matter. Unlike conventional guided EM waves that do not benefit from topological protection, TPSWs are shown to experience multi-wavelength reflection-free time delays when detoured around sharply-curved paths, thus offering a unique paradigm for compact and efficient wave buffers and other devices.
A Role for Nuclear Actin in HDAC 1 and 2 Regulation
Authors: Serebryannyy Leonid A. , Cruz Christina M. , de Lanerolle Primal 
Published: June 2016

AbstractClass I histone deacetylases (HDACs) are known to remove acetyl groups from histone tails. This liberates positive charges on the histone tail and allows for tighter winding of DNA, preventing transcription factor binding and gene activation. Although the functions of HDAC proteins are becoming apparent both biochemically and clinically, how this class of proteins is regulated remains poorly understood. We identified a novel interaction between nuclear actin and HDAC 1 and HDAC 2. Nuclear actin has been previously shown to interact with a growing list of nuclear proteins including chromatin remodeling complexes, transcription factors and RNA polymerases. We find that monomeric actin is able to bind the class I HDAC complex. Furthermore, increasing the concentration of actin in HeLa nuclear extracts was able to suppress overall HDAC function. Conversely, polymerizing nuclear actin increased HDAC activity and decreased histone acetylation. Moreover, the interaction between class I HDACs and nuclear actin was found to be activity dependent. Together, our data suggest nuclear actin is able to regulate HDAC 1 and 2 activity.
Amber Light (590 nm) Induces the Breakdown of Lipid Droplets through Autophagy-Related Lysosomal Degradation in Differentiated Adipocytes
Authors: Choi Min Sik , Kim Hyoung-June , Ham Mira , Choi Dong-Hwa , Lee Tae Ryong , Shin Dong Wook 
Published: June 2016

AbstractLipolysis in the adipocytes provides free fatty acids for other tissues in response to the energy demand. With the rapid increase in obesity-related diseases, finding novel stimuli or mechanisms that regulate lipid metabolism becomes important. We examined the effects of visible light (410, 457, 505, 530, 590, and 660 nm) irradiation on lipolysis regulation in adipocytes differentiated from human adipose-derived stem cells (ADSCs). Interestingly, 590 nm (amber) light irradiation significantly reduced the concentration of lipid droplets (LDs). We further investigated the lipolytic signaling pathways that are involved in 590 nm light irradiation-induced breakdown of LDs. Immunoblot analysis revealed that 590 nm light irradiation-induced phosphorylation of hormone-sensitive lipase (HSL) was insufficient to promote reduction of LDs. We observed that 590 nm light irradiation decreased the expression of perilipin 1. We found that 590 nm light irradiation, but not 505 nm, induced conversion of LC3 I to LC3 II, a representative autophagic marker. We further demonstrated that the lysosomal inhibitors leupeptin/NH4Cl inhibited 590 nm light irradiation-induced reduction of LDs in differentiated adipocytes. Our data suggest that 590 nm light irradiation-induced LD breakdown is partially mediated by autophagy-related lysosomal degradation, and can be applied in clinical settings to reduce obesity.
Visualising the strain distribution in suspended two-dimensional materials under local deformation
Authors: Elibol Kenan , Bayer Bernhard C. , Hummel Stefan , Kotakoski Jani , Argentero Giacomo , Meyer Jannik C. 
Published: June 2016

AbstractWe demonstrate the use of combined simultaneous atomic force microscopy (AFM) and laterally resolved Raman spectroscopy to study the strain distribution around highly localised deformations in suspended two-dimensional materials. Using the AFM tip as a nanoindentation probe, we induce localised strain in suspended few-layer graphene, which we adopt as a two-dimensional membrane model system. Concurrently, we visualise the strain distribution under and around the AFM tip in situ using hyperspectral Raman mapping via the strain-dependent frequency shifts of the few-layer graphene’s G and 2D Raman bands. Thereby we show how the contact of the nm-sized scanning probe tip results in a two-dimensional strain field with μm dimensions in the suspended membrane. Our combined AFM/Raman approach thus adds to the critically required instrumental toolbox towards nanoscale strain engineering of two-dimensional materials.
Mitigating wildfire carbon loss in managed northern peatlands through restoration
Authors: Granath Gustaf , Moore Paul A. , Lukenbach Maxwell C. , Waddington James M. 
Published: June 2016

AbstractNorthern peatlands can emit large amounts of carbon and harmful smoke pollution during a wildfire. Of particular concern are drained and mined peatlands, where management practices destabilize an array of ecohydrological feedbacks, moss traits and peat properties that moderate water and carbon losses in natural peatlands. Our results demonstrate that drained and mined peatlands in Canada and northern Europe can experience catastrophic deep burns (>200 t C ha−1 emitted) under current weather conditions. Furthermore, climate change will cause greater water losses in these peatlands and subject even deeper peat layers to wildfire combustion. However, the rewetting of drained peatlands and the restoration of mined peatlands can effectively lower the risk of these deep burns, especially if a new peat moss layer successfully establishes and raises peat moisture content. We argue that restoration efforts are a necessary measure to mitigate the risk of carbon loss in managed peatlands under climate change.
A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation
Authors: del Val Ioscani Jimenez , Polizzi Karen M. , Kontoravdi Cleo 
Published: June 2016

AbstractGlycosylation greatly influences the safety and efficacy of many of the highest-selling recombinant therapeutic proteins (rTPs). In order to define optimal cell culture feeding strategies that control rTP glycosylation, it is necessary to know how nucleotide sugars (NSs) are consumed towards host cell and rTP glycosylation. Here, we present a theoretical framework that integrates the reported glycoproteome of CHO cells, the number of N-linked and O-GalNAc glycosylation sites on individual host cell proteins (HCPs), and the carbohydrate content of CHO glycosphingolipids to estimate the demand of NSs towards CHO cell glycosylation. We have identified the most abundant N-linked and O-GalNAc CHO glycoproteins, obtained the weighted frequency of N-linked and O-GalNAc glycosites across the CHO cell proteome, and have derived stoichiometric coefficients for NS consumption towards CHO cell glycosylation. By combining the obtained stoichiometric coefficients with previously reported data for specific growth and productivity of CHO cells, we observe that the demand of NSs towards glycosylation is significant and, thus, is required to better understand the burden of glycosylation on cellular metabolism. The estimated demand of NSs towards CHO cell glycosylation can be used to rationally design feeding strategies that ensure optimal and consistent rTP glycosylation.
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor
Authors: Chen Hong , Yang Georgiana Zong Xin , Getachew Hoheteberhan , Acosta Camilo , Sierra Sánchez Carlos , Konofagou Elisa E. 
Published: June 2016

AbstractThe objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.
Physiological and molecular evidence of differential short-term heat tolerance in Mediterranean seagrasses
Authors: Marín-Guirao Lazaro , Ruiz Juan M. , Dattolo Emanuela , Garcia-Munoz Rocio , Procaccini Gabriele 
Published: June 2016

AbstractThe increase in extreme heat events associated to global warming threatens seagrass ecosystems, likely by affecting key plant physiological processes such as photosynthesis and respiration. Understanding species’ ability to acclimate to warming is crucial to better predict their future trends. Here, we study tolerance to warming in two key Mediterranean seagrasses, Posidonia oceanica and Cymodocea nodosa. Stress responses of shallow and deep plants were followed during and after short-term heat exposure in mesocosms by coupling photo-physiological measures with analysis of expression of photosynthesis and stress-related genes. Contrasting tolerance and capacity to heat acclimation were shown by shallow and deep P. oceanica ecotypes. While shallow plants acclimated through respiratory homeostasis and activation of photo-protective mechanisms, deep ones experienced photosynthetic injury and impaired carbon balance. This suggests that P. oceanica ecotypes are thermally adapted to local conditions and that Mediterranean warming will likely diversely affect deep and shallow meadow stands. On the other hand, contrasting mechanisms of heat-acclimation were adopted by the two species. P. oceanica regulates photosynthesis and respiration at the level of control plants while C. nodosa balances both processes at enhanced rates. These acclimation discrepancies are discussed in relation to inherent attributes of the two species.
On the energy scale involved in the metal to insulator transition of quadruple perovskite EuCu3Fe4O12: infrared spectroscopy and ab-initio calculations
Authors: Brière B. , Kalinko A. , Yamada I. , Roy P. , Brubach J. B. , Sopracase R. , Zaghrioui M. , Phuoc V. Ta 
Published: June 2016

AbstractOptical measurements were carried out by infrared spectroscopy on AA′3B4O12 A-site ordered quadruple perovskite EuCu3Fe4O12 (microscopic sample) as function of temperature. At 240 K (=TMI), EuCu3Fe4O12 undergoes a very abrupt metal to insulator transition, a paramagnetic to antiferromagnetic transition and an isostructural transformation with an abrupt large volume expansion. Above TMI, optical conductivity reveals a bad metal behavior and below TMI, an insulating phase with an optical gap of 125 meV is observed. As temperature is decreased, a large and abrupt spectral weight transfer toward an energy scale larger than 1 eV is detected. Concurrently, electronic structure calculations for both high and low temperature phases were compared to the optical conductivity results giving a precise pattern of the transition. Density of states and computed optical conductivity analysis identified Cu3dxy, Fe3d and O2p orbitals as principal actors of the spectral weight transfer. The present work constitutes a first step to shed light on EuCu3Fe4O12 electronic properties with optical measurements and ab-initio calculations.
Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders
Authors: Sakai Kaori , Shoji Hirotaka , Kohno Takao , Miyakawa Tsuyoshi , Hattori Mitsuharu 
Published: June 2016

AbstractThe secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder and autism spectrum disorder.
Encoding of mechanical nociception differs in the adult and infant brain
Authors: Fabrizi Lorenzo , Verriotis Madeleine , Williams Gemma , Lee Amy , Meek Judith , Olhede Sofia , Fitzgerald Maria 
Published: June 2016

AbstractNewborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain.