bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α
Authors: Wang Qirui , He Zhenqiang , Huang Menggui , Liu Tianrun , Wang Yanling , Xu Haineng , Duan Hao , Ma Peihong , Zhang Lin , Zamvil Scott S. , Hidalgo Juan , Zhang Zhenfeng , O’Rourke Donald M. , Dahmane Nadia , Brem Steven , Mou Yonggao , Gong Yanqing , Fan Yi 
Published: February 2018

AbstractSpatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors.
SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α
Authors: Mira Emilia , Carmona-Rodríguez Lorena , Pérez-Villamil Beatriz , Casas Josefina , Fernández-Aceñero María Jesús , Martínez-Rey Diego , Martín-González Paula , Heras-Murillo Ignacio , Paz-Cabezas Mateo , Tardáguila Manuel , Oury Tim D. , Martín-Puig Silvia , Lacalle Rosa Ana , Fabriás Gemma , Díaz-Rubio Eduardo , Mañes Santos 
Published: February 2018

AbstractOne drawback of chemotherapy is poor drug delivery to tumor cells, due in part to hyperpermeability of the tumor vasculature. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme usually repressed in the tumor milieu. Here we show that specific SOD3 re-expression in tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) delivery into and chemotherapeutic effect on tumors. Enhanced SOD3 activity fostered perivascular nitric oxide accumulation and reduced vessel leakage by inducing vascular endothelial cadherin (VEC) transcription. SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2α (HIF-2α) stability and enhanced its binding to a specific VEC promoter region. EC-specific HIF-2α ablation prevented both the SOD3-mediated increase in VEC transcription and the enhanced Doxo effect. SOD3, VEC, and HIF-2α levels correlated positively in primary colorectal cancers, which suggests a similar interconnection of these proteins in human malignancy.
Hemimetabolous genomes reveal molecular basis of termite eusociality
Authors: Harrison Mark C. , Jongepier Evelien , Robertson Hugh M. , Arning Nicolas , Bitard-Feildel Tristan , Chao Hsu , Childers Christopher P. , Dinh Huyen , Doddapaneni Harshavardhan , Dugan Shannon , Gowin Johannes , Greiner Carolin , Han Yi , Hu Haofu , Hughes Daniel S. T. , Huylmans Ann-Kathrin , Kemena Carsten , Kremer Lukas P. M. , Lee Sandra L. , Lopez-Ezquerra Alberto , Mallet Ludovic , Monroy-Kuhn Jose M. , Moser Annabell , Murali Shwetha C. , Muzny Donna M. , Otani Saria , Piulachs Maria-Dolors , Poelchau Monica , Qu Jiaxin , Schaub Florentine , Wada-Katsumata Ayako , Worley Kim C. , Xie Qiaolin , Ylla Guillem , Poulsen Michael , Gibbs Richard A. , Schal Coby , Richards Stephen , Belles Xavier , Korb Judith , Bornberg-Bauer Erich 
Published: February 2018

AbstractAround 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.
Clonal genome evolution and rapid invasive spread of the marbled crayfish
Authors: Gutekunst Julian , Andriantsoa Ranja , Falckenhayn Cassandra , Hanna Katharina , Stein Wolfgang , Rasamy Jeanne , Lyko Frank 
Published: February 2018

AbstractThe marbled crayfish Procambarus virginalis is a unique freshwater crayfish characterized by very recent speciation and parthenogenetic reproduction. Marbled crayfish also represent an emerging invasive species and have formed wild populations in diverse freshwater habitats. However, our understanding of marbled crayfish biology, evolution and invasive spread has been hampered by the lack of freshwater crayfish genome sequences. We have now established a de novo draft assembly of the marbled crayfish genome. We determined the genome size at approximately 3.5 gigabase pairs and identified >21,000 genes. Further analysis confirmed the close relationship to the genome of the slough crayfish, Procambarusfallax, and also established a triploid AA’B genotype with a high level of heterozygosity. Systematic fieldwork and genotyping demonstrated the rapid expansion of marbled crayfish on Madagascar and established the marbled crayfish as a potent invader of freshwater ecosystems. Furthermore, comparative whole-genome sequencing demonstrated the clonality of the population and their genetic identity with the oldest known stock from the German aquarium trade. Our study closes an important gap in the phylogenetic analysis of animal genomes and uncovers the unique evolutionary history of an emerging invasive species.
Anisotropic Friedel oscillations in graphene-like materials: The Dirac point approximation in wave-number dependent quantities revisited
Authors: Farajollahpour Tohid , Khamouei Shirin , Shateri Shabnam Safari , Phirouznia Arash 
Published: February 2018

AbstractFriedel oscillations of the graphene-like materials are investigated theoretically for low and intermediate Fermi energies. Numerical calculations have been performed within the random phase approximation. It was demonstrated that for intra-valley transitions the contribution of the different Dirac points in the wave-number dependent quantities is determined by the orientation of the wave-number in k-space. Therefore, identical contribution of the different Dirac points is not automatically guaranteed by the degeneracy of the Hamiltonian at these points. Meanwhile, it was shown that the contribution of the inter-valley transitions is always anisotropic even when the Dirac points coincide with the Fermi level (E
F
= 0). This means that the Dirac point approximation based studies could give the correct physics only at long wave length limit. The anisotropy of the static dielectric function reveals different contribution of the each Dirac point. Additionally, the anisotropic k-space dielectric function results in anisotropic Friedel oscillations in graphene-like materials. Increasing the Rashba interaction strength slightly modifies the Friedel oscillations in this family of materials. Anisotropy of the dielectric function in k-space is the clear manifestation of band anisotropy in the graphene-like systems.
Independent estimates of marine population connectivity are more concordant when accounting for uncertainties in larval origins
Authors: Nolasco R. , Gomes I. , Peteiro L. , Albuquerque R. , Luna T. , Dubert J. , Swearer S. E. , Queiroga H. 
Published: February 2018

AbstractMarine larval dispersal is a complex biophysical process that depends on the effects of species biology and oceanography, leading to logistical difficulties in estimating connectivity among populations of marine animals with biphasic life cycles. To address this challenge, the application of multiple methodological approaches has been advocated, in order to increase confidence in estimates of population connectivity. However, studies seldom account for sources of uncertainty associated with each method, which undermines a direct comparative approach. In the present study we explicitly account for the statistical uncertainty in observed connectivity matrices derived from elemental chemistry of larval mussel shells, and compare these to predictions from a biophysical model of dispersal. To do this we manipulate the observed connectivity matrix by applying different confidence levels to the assignment of recruits to source populations, while concurrently modelling the intrinsic misclassification rate of larvae to known sources. We demonstrate that the correlation between the observed and modelled matrices increases as the number of observed recruits classified as unknowns approximates the observed larval misclassification rate. Using this approach, we show that unprecedented levels of concordance in connectivity estimates (r = 0.96) can be achieved, and at spatial scales (20–40 km) that are ecologically relevant.
Phenotyping field-state wheat root system architecture for root foraging traits in response to environment×management interactions
Authors: Chen Xinxin , Li Yinian , He Ruiyin , Ding Qishuo 
Published: February 2018

AbstractAn important aspect of below-ground crop physiology is its root foraging performance, which is inherently related to root system architecture (RSA). A 2-yr field experiment was conducted and the field-state wheat RSA was phenotyped for root foraging trait (RFT). Four RSA-derived traits, i.e. Root horizontal angle (RHA), axial root expansion volume (AREV), RSA convex hull volume (CHV) and effective volume per unit root length (EVURL), were analyzed for RFTs in response to environment × management interactions. Results showed a dynamical RHA process but without statistical difference both within crop seasons and tillage treatments. AREV increased with root developmental stages, revealing an overall better root performance in the first year. However, tillage treatments did not induce observed difference within both crop seasons. CHV varied drastically from year to year and between tillage treatments, correlating well to the root length, but not with RHA. EVURL was both sensitive to tillage treatments and crop seasons, being a potential indicator for RFT. Above all, tillage effect on RFT was statistically far less than that induced by crop seasons. Pro/E assisted modeling can be used as an effective means for phenotyping integrated, RSA-derived, RFTs for root foraging response to induced environment × management interactions.
A Global Perspective on Sulfur Oxide Controls in Coal-Fired Power Plants and Cardiovascular Disease
Authors: Lin Cheng-Kuan , Lin Ro-Ting , Chen Pi-Cheng , Wang Pu , De Marcellis-Warin Nathalie , Zigler Corwin , Christiani David C. 
Published: February 2018

AbstractSulfur oxides (SOx), particularly SO2 emitted by coal-fired power plants, produce long-term risks for cardiovascular disease (CVD). We estimated the relative risks of CVD and ischemic heart disease (IHD) attributable to SOx emission globally. National SOx reduction achieved by emissions control systems was defined as the average SOx reduction percentage weighted by generating capacities of individual plants in a country. We analyzed the relative risk of CVD incidence associated with national SOx reduction for 13,581 coal-fired power-generating units in 79 countries. A 10% decrease in SOx emission was associated with 0.28% (males; 95%CI = −0.39%~0.95%) and 1.69% (females; 95%CI = 0.99%~2.38%) lower CVD risk. The effects on IHD were > 2 times stronger among males than females (2.78%, 95%CI = 1.99%~3.57% vs. 1.18%, 95%CI = 0.19%~2.17%). Further, 1.43% (males) and 8.00% (females) of CVD cases were attributable to suboptimal SOx reduction. Thus, enhancing regulations on SOx emission control represents a target for national and international intervention to prevent CVD.
Csde1 binds transcripts involved in protein homeostasis and controls their expression in an erythroid cell line
Authors: Moore Kat S. , Yagci Nurcan , van Alphen Floris , Paolini Nahuel A. , Horos Rastislav , Held Ntsiki M. , Houtkooper Riekelt H. , van den Akker Emile , Meijer Alexander B. , ‘t Hoen Peter A. C. , von Lindern Marieke 
Published: February 2018

AbstractExpression of the RNA-binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis compared to other hematopoietic lineages. Csde1 expression is impaired in the severe congenital anemia Diamond Blackfan Anemia (DBA), and reduced expression of Csde1 in healthy erythroblasts impaired their proliferation and differentiation. To investigate the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1 in erythroid cells. These mainly encoded proteins involved in ribogenesis, mRNA translation and protein degradation, but also proteins associated with the mitochondrial respiratory chain and mitosis. Crispr/Cas9-mediated deletion of the first cold shock domain of Csde1 affected RNA expression and/or protein expression of Csde1-bound transcripts. For instance, protein expression of Pabpc1 was enhanced while Pabpc1 mRNA expression was reduced indicating more efficient translation of Pabpc1 followed by negative feedback on mRNA stability. Overall, the effect of reduced Csde1 function on mRNA stability and translation of Csde1-bound transcripts was modest. Clones with complete loss of Csde1, however, could not be generated. We suggest that Csde1 is involved in feed-back control in protein homeostasis and that it dampens stochastic changes in mRNA expression.
No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years
Authors: Mok Hoi Ping , Norton Nicholas J. , Hirst Jack C , Fun Axel , Bandara Mikaila , Wills Mark R. , Lever Andrew M. L. 
Published: February 2018

AbstractThe persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability. To study viral evolution in a physiologically relevant population of latent viruses, we repeatedly performed virus outgrowth assays on a stably treated HIV positive patient over two years and sequenced the reactivated latent viruses. We sought evidence of increasing sequence pairwise distances with time as evidence of ongoing viral replication. 64 reactivatable latent viral sequences were obtained over 103 weeks. We did not observe an increase in genetic distance of the sequences with the time elapsed between sampling. No evolution could be discerned in these reactivatable latent viruses. Thus, in this patient, the contribution of low-level replication to the maintenance of the latent reservoir detectable in the blood compartment is limited.
The Importance of Phonons with Negative Phase Quotient in Disordered Solids
Authors: Seyf Hamid Reza , Lv Wei , Rohskopf Andrew , Henry Asegun 
Published: February 2018

AbstractCurrent understanding of phonons is based on the phonon gas model (PGM), which is best rationalized for crystalline materials. However, most of the phonons/modes in disordered materials have a different character and thus may contribute to heat conduction in a fundamentally different way than is described by PGM. For the modes in crystals, which have sinusoidal character, one can separate the modes into two primary categories, namely acoustic and optical modes. However, for the modes in disordered materials, such designations may no longer rigorously apply. Nonetheless, the phase quotient (PQ) is a quantity that can be used to evaluate whether a mode more so shares a distinguishing property of acoustic vibrations manifested as a positive PQ, or a distinguishing property of an optical vibrations manifested as negative PQ. In thinking about this characteristic, there is essentially no intuition regarding the role of positive vs. negative PQ vibrational modes in disordered solids. Given this gap in understanding, herein we studied the respective contributions to thermal conductivity for several disordered solids as a function of PQ. The analysis sheds light on the importance of optical like/negative PQ modes in structurally/compositionally disordered solids, whereas in crystalline materials, the contributions of optical modes are usually small.
Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
Authors: Hernando Elsa , Capurro Valeria , Cossu Claudia , Fiore Michele , García-Valverde María , Soto-Cerrato Vanessa , Pérez-Tomás Ricardo , Moran Oscar , Zegarra-Moran Olga , Quesada Roberto 
Published: February 2018

AbstractAnion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.
Role of Precursor Carbides for Graphene Growth on Ni(111)
Authors: Rameshan Raffael , Vonk Vedran , Franz Dirk , Drnec Jakub , Penner Simon , Garhofer Andreas , Mittendorfer Florian , Stierle Andreas , Klötzer Bernhard 
Published: February 2018

AbstractSurface X-ray Diffraction was used to study the transformation of a carbon-supersaturated carbidic precursor toward a complete single layer of graphene in the temperature region below 703 K without carbon supply from the gas phase. The excess carbon beyond the 0.45  monolayers of C atoms within a single Ni2C layer is accompanied by sharpened reflections of the |4772| superstructure, along with ring-like diffraction features resulting from non-coincidence rotated Ni2C-type domains. A dynamic Ni2C reordering process, accompanied by slow carbon loss to subsurface regions, is proposed to increase the Ni2C 2D carbide long-range order via ripening toward coherent domains, and to increase the local supersaturation of near-surface dissolved carbon required for spontaneous graphene nucleation and growth. Upon transformation, the intensities of the surface carbide reflections and of specific powder-like diffraction rings vanish. The associated change of the specular X-ray reflectivity allows to quantify a single, fully surface-covering layer of graphene (2 ML C) without diffraction contributions of rotated domains. The simultaneous presence of top-fcc and bridge-top configurations of graphene explains the crystal truncation rod data of the graphene-covered surface. Structure determination of the |4772| precursor surface-carbide using density functional theory is in perfect agreement with the experimentally derived X-ray structure factors.
Impact of erroneous meal insulin bolus with dual-hormone artificial pancreas using a simplified bolus strategy - A randomized controlled trial
Authors: Gingras Véronique , Smaoui Mohamed Raef , Cameli Charlotte , Messier Virginie , Ladouceur Martin , Legault Laurent , Rabasa-Lhoret Rémi 
Published: February 2018

AbstractPostprandial glucose control remains challenging for patients with type 1 diabetes (T1D). A simplified meal bolus approach with a dual-hormone (insulin and glucagon) closed-loop system (DH-CLS) has been tested; yet, the impact of categorization errors with this strategy is unknown. The objective was to compare, in a randomized controlled inpatient trial, DH-CLS with the simplified meal bolus approach for two different meals properly categorized or overestimated. We tested, in patients with T1D, the simplified strategy with two standardized breakfasts (n = 10 per meal) adequately categorized or overestimated: (1) 75 g and (2) 45 g of carbohydrate. No difference was observed for percentage of time <4.0 mmol/L over a 4-hour post-meal period (primary outcome; median [IQR]: 0[0–0] vs. 0[0–0] for both comparisons, p = 0.47 and 0.31 for the 75 g and 45 g meals, respectively). Despite higher meal insulin boluses with overestimation for both meals (9.2 [8.2–9.6] vs. 8.1 [7.3–9.1] U and 8.4 [7.2–10.4] vs. 4.8 [3.7–5.6] U; p < 0.05), mean glycemia, percentage of time in target range and glucagon infusion did not differ. Additional scenarios were tested in silico with comparable results. These results suggest that the DH-CLS with a simplified meal bolus calculation is probably able to avoid hypoglycemia in the event of meal size misclassification.
Personalizing Androgen Suppression for Prostate Cancer Using Mathematical Modeling
Authors: Hirata Yoshito , Morino Kai , Akakura Koichiro , Higano Celestia S. , Aihara Kazuyuki 
Published: February 2018

AbstractUsing a dataset of 150 patients treated with intermittent androgen suppression (IAS) through a fixed treatment schedule, we retrospectively designed a personalized treatment schedule mathematically for each patient. We estimated 100 sets of parameter values for each patient by randomly resampling each patient’s time points to take into account the uncertainty for observations of prostate specific antigen (PSA). Then, we identified 3 types and classified patients accordingly: in type (i), the relapse, namely the divergence of PSA, can be prevented by IAS; in type (ii), the relapse can be delayed by IAS later than by continuous androgen suppression (CAS); in type (iii) IAS was not beneficial and therefore CAS would have been more appropriate in the long run. Moreover, we obtained a treatment schedule of hormone therapy by minimizing the PSA of 3 years later in the worst case scenario among the 100 parameter sets by searching exhaustively all over the possible treatment schedules. If the most frequent type among 100 sets was type (i), the maximal PSA tended to be kept less than 100 ng/ml longer in IAS than in CAS, while there was no statistical difference for the other cases. Thus, mathematically personalized IAS should be studied prospectively.