bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined obeticholic acid and elafibranor treatment promotes additive liver histological improvements in a diet-induced ob/ob mouse model of biopsy-confirmed NASH
Authors: Roth Jonathan D. , Veidal Sanne S. , Fensholdt Louise K. D. , Rigbolt Kristoffer T. G. , Papazyan Romeo , Nielsen Jens Christian , Feigh Michael , Vrang Niels , Young Mark , Jelsing Jacob , Adorini Luciano , Hansen Henrik H. 
Published: June 2019

AbstractObeticholic acid (OCA) and elafibranor (ELA) are selective and potent agonists for the farnesoid X receptor (FXR) and dual peroxisome proliferator-activated receptor α/δ (PPAR-α/δ), respectively. Both agents have demonstrated clinical efficacy in nonalcoholic steatohepatitis (NASH). The present study used OCA and ELA to compare the effects of mono- and combination therapies on metabolic and histological endpoints in Lepob/ob mice with established diet-induced and biopsy-confirmed NASH (ob/ob-NASH). ob/ob-NASH mice were fed the AMLN diet high in trans-fat, fructose and cholesterol for 15 weeks, whereafter they received vehicle, OCA (30 mg/kg, PO, QD), ELA (3, 10 mg/kg, PO, QD), or combinations (OCA + ELA) for eight weeks. Within-subject comparisons were performed on histomorphometric changes, including fractional area of liver fat, galectin-3 and Col1a1. OCA and ELA monotherapies improved all quantitative histopathological parameters and OCA + ELA combinations exerted additive effects on metabolic and histological endpoints. In agreement with their different molecular mechanisms of action, OCA and ELA monotherapies elicited distinct hepatic gene expression profiles and their combination led to profound transcriptome changes associated with further improvements in lipid handling and insulin signaling, suppression of immune responses and reduced extracellular matrix formation. In conclusion, these findings provide preclinical proof-of-concept for combined FXR and PPAR-α/δ agonist-based therapies in NASH.
Role of hole confinement in the recombination properties of InGaN quantum structures
Authors: Anikeeva M. , Albrecht M. , Mahler F. , Tomm J. W. , Lymperakis L. , Chèze C. , Calarco R. , Neugebauer J. , Schulz T. 
Published: June 2019

AbstractWe study the isolated contribution of hole localization for well-known charge carrier recombination properties observed in conventional, polar InGaN quantum wells (QWs). This involves the interplay of charge carrier localization and non-radiative transitions, a non-exponential decay of the emission and a specific temperature dependence of the emission, denoted as “s-shape”. We investigate two dimensional In0.25Ga0.75N QWs of single monolayer (ML) thickness, stacked in a superlattice with GaN barriers of 6, 12, 25 and 50 MLs. Our results are based on scanning and high-resolution transmission electron microscopy (STEM and HR-TEM), continuous-wave (CW) and time-resolved photoluminescence (TRPL) measurements as well as density functional theory (DFT) calculations. We show that the recombination processes in our structures are not affected by polarization fields and electron localization. Nevertheless, we observe all the aforementioned recombination properties typically found in standard polar InGaN quantum wells. Via decreasing the GaN barrier width to 6 MLs and below, the localization of holes in our QWs is strongly reduced. This enhances the influence of non-radiative recombination, resulting in a decreased lifetime of the emission, a weaker spectral dependence of the decay time and a reduced s-shape of the emission peak. These findings suggest that single exponential decay observed in non-polar QWs might be related to an increasing influence of non-radiative transitions.
Different phenotypic plastic responses to predators observed among aphid lineages specialized on different host plants
Authors: Sentis Arnaud , Bertram Raphaël , Dardenne Nathalie , Ramon-Portugal Felipe , Louit Ines , Le Trionnaire Gaël , Simon Jean-Christophe , Magro Alexandra , Pujol Benoit , Hemptinne Jean-Louis , Danchin Etienne 
Published: June 2019

AbstractThe role of intraspecific variation in the magnitude and direction of plastic responses in ecology and evolution is increasingly recognized. However, the factors underlying intraspecific variation in plastic responses remain largely unexplored, particularly for the hypothesis that the herbivores’ phenotypic response to predators might vary amongst lineages associated with different host plants. Here, we tested whether plant-specialized lineages of the pea aphid, Acyrthosiphon pisum, differed in their transgenerational phenotypic response to ladybird predators (i.e., the asexual production of winged offspring by wingless mothers). In a full factorial laboratory experiment, we found that six aphid clonal lineages each specialized either on alfalfa or clover significantly differed in their transgenerational phenotypic response to predators. Some lineages produced an increased number of winged aphids in predator presence while others did not respond. Aphid lineages specialized on alfalfa had stronger phenotypic responses to predators than those specialized on clover. Although we tested only six aphid lineages from two biotypes, our results imply that intraspecific variation in prey phenotypic response of herbivores to predators differs amongst lineages specialized on different host plants. Our findings therefore raise the question of the influence of plant specialization in shaping herbivore phenotypic responses, and highlight the need to consider multi-trophic interactions to understand the causes and consequences of intraspecific variation in complex phenotypic traits.
Persistent effects of cyclic adenosine monophosphate are directly responsible for maintaining a neural network state
Authors: Perkins Matthew H. , Weiss Klaudiusz R. , Cropper Elizabeth C. 
Published: June 2019

AbstractNetwork states are often determined by modulators that alter the synaptic and cellular properties of the constituent neurons. Frequently neuromodulators act via second messengers, consequently their effects can persist. This persistence at the cellular/molecular level determines the maintenance of the state at the network level. Here we study a feeding network in Aplysia. In this network, persistent modulation supports the maintenance of an ingestive state, biasing the network to generate ingestive motor programs. Neuropeptides that exert cyclic adenosine monophosphate (cAMP) dependent effects play an important role in inducing the ingestive state. Most commonly, modulatory effects exerted through cAMP signaling are persistent as a consequence of PKA activation. This is not the case in the neurons we study. Instead maintenance of the network state depends on the persistence of cAMP itself. Data strongly suggest that this is a consequence of the direct activation of a cyclic nucleotide gated current.
BioTarget: A Computational Framework Identifying Cancer Type Specific Transcriptional Targets of Immune Response Pathways
Authors: Hoang Tham H. , Zhao Yue , Lam Yiu , Piekos Stephanie , Han Yueh-Chiang , Reilly Cameron , Joshi Pujan , Hong Seung-Hyun , Sung Chang Ohk , Giardina Charles , Shin Dong-Guk 
Published: June 2019

AbstractTranscriptome data can provide information on signaling pathways active in cancers, but new computational tools are needed to more accurately quantify pathway activity and identify tissue-specific pathway features. We developed a computational method called “BioTarget” that incorporates ChIP-seq data into cellular pathway analysis. This tool relates the expression of transcription factor TF target genes (based on ChIP-seq data) with the status of upstream signaling components for an accurate quantification of pathway activity. This analysis also reveals TF targets expressed in specific contexts/tissues. We applied BioTarget to assess the activity of TBX21 and GATA3 pathways in cancers. TBX21 and GATA3 are TF regulators that control the differentiation of T cells into Th1 and Th2 helper cells that mediate cell-based and humoral immune responses, respectively. Since tumor immune responses can impact cancer progression, the significance of our pathway scores should be revealed by effective patient stratification. We found that low Th1/Th2 activity ratios were associated with a significantly poorer survival of stomach and breast cancer patients, whereas an unbalanced Th1/Th2 response was correlated with poorer survival of colon cancer patients. Lung adenocarcinoma and lung squamous cell carcinoma patients had the lowest survival rates when both Th1 and Th2 responses were high. Our method also identified context-specific target genes for TBX21 and GATA3. Applying the BioTarget tool to BCL6, a TF associated with germinal center lymphocytes, we observed that patients with an active BCL6 pathway had significantly improved survival for breast, colon, and stomach cancer. Our findings support the effectiveness of the BioTarget tool for transcriptome analysis and point to interesting associations between some immune-response pathways and cancer progression.
Hyaluronan and LYVE-1 and allograft function in lung transplantation recipients
Authors: Courtwright Andrew M. , Lamattina Anthony M. , Louis Pierce H. , Trindade Anil J. , Burkett Patrick , Imani Jewel , Shrestha Shikshya , Divo Miguel , Keller Steve , Rosas Ivan O. , Goldberg Hilary J. , El-Chemaly Souheil 
Published: June 2019

AbstractHyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients. This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). Chronic lung allograft dysfunction (CLAD)-free survival was also evaluated based on HA and LYVE-1 levels. 78 recipients were enrolled with a total of 115 diagnostic biopsies and 1.5 years of median follow-up. Serum HA was correlated with BAL HA (r = 0.25, p = 0.01) and with serum LYVE-1 (r = 0.32, p = 0.002). There was significant variation in HA and LYVE-1 over time, regardless of ACR status. Levels of serum HA (median 74.7 vs 82.7, p = 0.69), BAL HA (median 149.4 vs 134.5, p = 0.39), and LYVE-1 (mean 190.2 vs 183.8, p = 0.72) were not associated with ACR. CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3–7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2–3.6, p = 0.93). These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients.
Experimental and empirical evidence shows that reducing weed control in winter cereal fields is a viable strategy for farmers
Authors: Catarino Rui , Gaba Sabrina , Bretagnolle Vincent 
Published: June 2019

AbstractModern agriculture needs a paradigm shift to make the world’s food production sustainable while mitigating social and environmental externalities. Although various policies to limit the use of agrochemicals have recently been implemented in the European Union, the use of both herbicides and fertilizers has remained fairly constant. Farmers are assumed to behave optimally, producing the best they can, given the agronomic constraints of their fields. Based on this assumption, reducing agrochemicals should inevitably have negative effects on food production, or reduce farmers’ incomes. Coupling empirical analysis based on field surveys and experimental trials where weed management and nitrogen input were manipulated in the same production fields and under real farming conditions, we demonstrate that high use of N fertiliser or intense weed control slightly increase yields, but that this increase is not enough to offset the additional costs incurred by their use. Our experimental design allowed inputs to be varied in a two-factor design, along a gradient spanning from organic to highly intensive farming, while holding all other conditions constant and thus avoiding confounding effects. Quantification of crop yields and gross margins from winter cereal farming showed that reducing dependence on weed management may not hamper cereal production in this system, and is economically profitable at the field level on the short term. Our study thus contributes to addressing a key gap in our economic knowledge, and gives hope for implementing win-win strategies for farmers and the environment.
Sex ratios at birth vary with environmental harshness but not maternal condition
Authors: Schacht Ryan , Tharp Douglas , Smith Ken R. 
Published: June 2019

AbstractThe sex ratio at birth (SRB) may be patterned by maternal condition and/or environmental stressors. However, despite decades of research, empirical results from across the social and biological sciences are equivocal on this topic. Using longitudinal individual-level data from a US population during the interwar period (1918–1939), inclusive of three distinct eras (Spanish Flu, Roaring ‘20 s, and the Great Depression), we evaluate predictions from two theoretical frameworks used to study patterning in SRB – (1) ‘frail males’ and (2) adaptive sex-biased investment theory (Trivers-Willard). The first approach centers on greater male susceptibility to exogenous stressors and argues that offspring survival should be expected to differ between ‘good’ and ‘bad’ times. The second approach contends that mothers themselves play a direct role in manipulating offspring SRB, and that those in better condition should invest more in sons. In-line with ‘frail male’ predictions, we find that boys are less likely to be born during the environmentally challenging times of the Spanish Flu and Great Depression. However, we find no evidence that maternal condition is associated with sex ratios at birth, a result inconsistent with the Trivers-Willard hypothesis.
Genes functioned in kleptoplastids of Dinophysis are derived from haptophytes rather than from cryptophytes
Authors: Hongo Yuki , Yabuki Akinori , Fujikura Katsunori , Nagai Satoshi 
Published: June 2019

AbstractToxic dinoflagellates belonging to the genus Dinophysis acquire plastids indirectly from cryptophytes through the consumption of the ciliate Mesodinium rubrum. Dinophysis acuminata harbours three genes encoding plastid-related proteins, which are thought to have originated from fucoxanthin dinoflagellates, haptophytes and cryptophytes via lateral gene transfer (LGT). Here, we investigate the origin of these plastid proteins via RNA sequencing of species related to D. fortii. We identified 58 gene products involved in porphyrin, chlorophyll, isoprenoid and carotenoid biosyntheses as well as in photosynthesis. Phylogenetic analysis revealed that the genes associated with chlorophyll and carotenoid biosyntheses and photosynthesis originated from fucoxanthin dinoflagellates, haptophytes, chlorarachniophytes, cyanobacteria and cryptophytes. Furthermore, nine genes were laterally transferred from fucoxanthin dinoflagellates, whose plastids were derived from haptophytes. Notably, transcription levels of different plastid protein isoforms varied significantly. Based on these findings, we put forth a novel hypothesis regarding the evolution of Dinophysis plastids that ancestral Dinophysis species acquired plastids from haptophytes or fucoxanthin dinoflagellates, whereas LGT from cryptophytes occurred more recently. Therefore, the evolutionary convergence of genes following LGT may be unlikely in most cases.
Pharmacologic targeting of β-catenin improves fracture healing in old mice
Authors: Kwak Yoon Hae , Barrientos Tomasa , Furman Bridgette , Zhang Hazel , Puviindran Vijitha , Cutcliffe Hattie , Herfarth Jonas , Nwankwo Eugene , Alman Benjamin A. 
Published: June 2019

Abstractβ-catenin protein needs to be precisely regulated for effective fracture repair. The pace of fracture healing slows with age, associated with a transient increase in β-catenin during the initial phase of the repair process. Here we examined the ability of pharmacologic agents that target β-catenin to improve the quality of fracture repair in old mice. 20 month old mice were treated with Nefopam or the tankyrase inhibitor XAV939 after a tibia fracture. Fractures were examined 21 days later by micro-CT and histology, and 28 days later using mechanical testing. Daily treatment with Nefopam for three or seven days but not ten days improved the amount of bone present at the fracture site, inhibited β-catenin protein level, and increased colony forming units osteoblastic from bone marrow cells. At 28 days, treatment increased the work to fracture of the injured tibia. XAV939 had a more modest effect on β-catenin protein, colony forming units osteoblastic, and the amount of bone at the fracture site. This data supports the notion that high levels of β-catenin in the early phase of fracture healing in old animals slows osteogenesis, and suggests a pharmacologic approach that targets β-catenin to improve fracture repair in the elderly.
Supercontinuum generation by co-filamentation of two color femtosecond laser pulses
Authors: Vengris M. , Garejev N. , Tamošauskas G. , Čepėnas A. , Rimkus L. , Varanavičius A. , Jukna V. , Dubietis A. 
Published: June 2019

AbstractIn this paper, we experimentally investigate supercontinuum generation via collinear two-color filamentation in sapphire crystal, by launching two femtosecond pulses at fundamental (1030 nm) and second harmonic (515 nm) wavelengths from an amplified Yb:KGW laser. By changing the time delay between the incident pulses, we observe dramatic changes in the supercontinuum spectrum, transmitted energy, position of the nonlinear focus and intensity distribution along the filamentinduced luminescence traces. In particular, we show that at some delays the two pump wavelengths can assist each other in generating supercontinuum, whilst at other delays large portions of the supercontinuum spectrum are completely extinguished. The transition between supercontinuum generation and its extinction occurs within a very short (20 fs) span of the delay times, despite the fact that the pump pulses are 220 fs long. We propose that the observed non-trivial spectral dynamics can be interpreted by a mechanism, where co-propagating two pump pulses perturb the nonlinear refractive properties of the medium via Kerr effect and generation of free electron plasma thereby affecting pulse splitting and pulse front steepening, which are the key players in the process of supercontinuum generation in a normally dispersive medium.
Genetic markers of lipid metabolism genes associated with low susceptibility to HCV infection
Authors: Real Luis Miguel , Macías Juan , Rivero-Juárez Antonio , Téllez Francisco , Merino Dolores , Moreno-Grau Sonia , Orellana Adelina , Gómez-Salgado Juan , Sáez María E. , Frías Mario , Corma-Gómez Anaïs , Merchante Nicolás , Ruiz Agustín , Caruz Antonio , Pineda Juan A. ,   GEHEP 012 study group, Fernández-Fuertes Marta , Iglesias María , Rincón Pilar 
Published: June 2019

AbstractDue to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17–1.75] relative-units [ru] versus 1.71 [1.00–2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.
Real time extended range prediction of heat waves over India
Authors: Mandal Raju , Joseph Susmitha , Sahai A. K. , Phani R. , Dey A. , Chattopadhyay R. , Pattanaik D. R. 
Published: June 2019

AbstractHeat waves over India occur during the months of March-June. This study aims at the real-time monitoring and prediction of heat waves using a multi-model dynamical ensemble prediction system developed at Indian Institute of Tropical Meteorology, India. For this, a criterion has been proposed based on the observed daily gridded maximum temperature (Tmax) datasets, which can be used for real-time prediction as well. A heat wave day is identified when either (1) Tmax (a)≥ its climatological 95th percentile (calculated from daily values during March-June and for 1981–2010), (b) >36 °C, and (c) its departure from normal is >3.5 °C, Or, (2) when the Tmax >44 °C. Three heat wave prone regions, namely, northwest, southeast and northwest-southeast regions are recognized and heat wave spells of minimum consecutive six days are identified objectively for each region during 1981–2018. It is noticed that the prediction system has reasonable skill in predicting the heat waves over heat wave prone regions of India. Forecast verification of heat wave spells during 2003–2018 reveals that the prediction system has great potential in providing overall indication about the onset, duration and demise of the forthcoming heat wave spell with sufficient lead time albeit with some spatio-temporal error.
Electrification in granular gases leads to constrained fractal growth
Authors: Singh Chamkor , Mazza Marco G. 
Published: June 2019

AbstractThe empirical observation of aggregation of dielectric particles under the influence of electrostatic forces lies at the origin of the theory of electricity. The growth of clusters formed of small grains underpins a range of phenomena from the early stages of planetesimal formation to aerosols. However, the collective effects of Coulomb forces on the nonequilibrium dynamics and aggregation process in a granular gas – a model representative of the above physical processes – have so far evaded theoretical scrutiny. Here, we establish a hydrodynamic description of aggregating granular gases that exchange charges upon collisions and interact via the long-ranged Coulomb forces. We analytically derive the governing equations for the evolution of granular temperature, charge variance, and number density for homogeneous and quasi-monodisperse aggregation. We find that, once the aggregates are formed, the granular temperature of the cluster population, the charge variance of the cluster population and the number density of the cluster population evolve in such a way that their non-dimensional combination obeys a physical constraint of nearly constant dimensionless ratio of characteristic electrostatic to kinetic energy. This constraint on the collective evolution of charged clusters is confirmed both by our theory and our detailed molecular dynamics simulations. The inhomogeneous aggregation of monomers and clusters in their mutual electrostatic field proceeds in a fractal manner. Our theoretical framework is extendable to more precise charge exchange mechanisms, a current focus of extensive experimentation. Furthermore, it illustrates the collective role of long-ranged interactions in dissipative gases and can lead to novel designing principles in particulate systems.