bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aescin-Cholesterol Complexes in DMPC Model Membranes: A DSC and Temperature-Dependent Scattering Study
Authors: Sreij Ramsia , Dargel Carina , Schweins Ralf , Prévost Sylvain , Dattani Rajeev , Hellweg Thomas 
Published: April 2019

AbstractThe saponin aescin, a mixture of triterpenoid saponins, is obtained from the seeds of the horse chestnut tree Aesculus hippocastanum. The β-form employed in this study is haemolytically active. The haemolytic activity results from the ability of aescin to form strong complexes with cholesterol in the red blood cell membrane. In this study, we provide a structural analysis on the complex formation of aescin and cholesterol when embedded in a phospholipid model membrane formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). In this work, the temperatures investigated extend from DMPC’s Lβ′ to its Lα phase in dependence of different amounts of the saponin (0–6 mol% for calorimetric and 0–1 mol% for structural analyses) and the steroid (1–10 mol%). At these aescin contents model membranes are conserved in the form of small unilamellar vesicles (SUVs) and major overall structural modifications are avoided. Additionally, interactions between aescin and cholesterol can be studied for both phase states of the lipid, the gel and the fluid state. From calorimetric experiments by differential scanning calorimetry (DSC), it could be shown that both, the steroid and the saponin content, have a significant impact on the cooperative phase transition behaviour of the DMPC molecules. In addition, it becomes clearly visible that the entire phase behaviour is dominated by phase separation which indeed also depends on the complexes formed between aescin and cholesterol. We show by various methods that the addition of cholesterol alters the impact of aescin on structural parameters ranging from the acyl chain correlation to vesicle-vesicle interactions. While the specific saponin-phospholipid interaction is reduced, addition of cholesterol leads to deformation of SUVs. The analyses of the structures formed were performed by wide-angle X-ray scattering (WAXS), small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS).
Stress transfer patterns and local seismicity related to reservoir water-level variations. A case study in central Costa Rica
Authors: Ruiz-Barajas S. , Santoyo M. A. , Benito Oterino M. B. , Alvarado G. E. , Climent A. 
Published: April 2019

AbstractThis study main aim was to analyse the spatio-temporal trend in seismicity recorded in the proximity of the Pirrís Reservoir (central Costa Rica), where impoundment for the purposes of filling the reservoir to its total volume (3,6 * 107 m3) started in 2011. We differentiated between the events that occurred before, during and after this filling operation. Using a seismic analysis, we sought to define and understand the effects which such reservoir operations have on seismic activity in the area. To this end, we evaluated the spatio-temporal evolution of Coulomb failure stress (ΔCFS) changes due to surface water load, and its correlation with seismicity. Overall, the results of this study provide a perspective of how the water load in the reservoir can affect the stress state in the close area. In our study case, we have detected: an increase in b-value after impoundment, an increment of rate for shallowest events (h ≤ 10 km), an increasing trend of higher magnitude events and a possible trigger effect on local faults. All these aspects could be useful to control the reservoir operations and to help in decision making in order to guarantee the safety of these critical emplacements.
Genomic insights into HSFs as candidate genes for high-temperature stress adaptation and gene editing with minimal off-target effects in flax
Authors: Saha Dipnarayan , Mukherjee Pranit , Dutta Sourav , Meena Kanti , Sarkar Surja Kumar , Mandal Asit Baran , Dasgupta Tapash , Mitra Jiban 
Published: April 2019

AbstractFlax (Linum usitatissimum) is a cool season crop commercially cultivated for seed oil and stem fibre production. A comprehensive characterization of the heat shock factor (HSF) candidate genes in flax can accelerate genetic improvement and adaptive breeding for high temperature stress tolerance. We report the genome-wide identification of 34 putative HSF genes from the flax genome, which we mapped on 14 of the 15 chromosomes. Through comparative homology analysis, we classified these genes into three broad groups, and sub-groups. The arrangement of HSF-specific protein motifs, DNA-binding domain (DBD) and hydrophobic heptad repeat (HR-A/B), and exon-intron boundaries substantiated the phylogenetic separation of these genes. Orthologous relationships and evolutionary analysis revealed that the co-evolution of the LusHSF genes was due to recent genome duplication events. Digital and RT-qPCR analyses provided significant evidence of the differential expression of the LusHSF genes in various tissues, at various developmental stages, and in response to high-temperature stress. The co-localization of diverse cis-acting elements in the promoters of the LusHSF genes further emphasized their regulatory roles in the abiotic stress response. We further confirmed DNA-binding sites on the LusHSF proteins and designed guide RNA sequences for gene editing with minimal off-target effects. These results will hasten functional investigations of LusHSFs or assist in devising genome engineering strategies to develop high-temperature stress tolerant flax cultivars.
Genetic association of LPL rs1121923 and rs258 with plasma TG and VLDL levels
Authors: Al-Bustan Suzanne A. , Al-Serri Ahmad , Alnaqeeb Majed A. , Annice Babitha G. , Mojiminiyi Olusegun 
Published: April 2019

AbstractLipoprotein lipase (LPL) is a rate-limiting enzyme for the hydrolysis of triglycerides (TG). Hundreds of genetic variants including single nucleotide polymorphisms have been identified across the 30Kb gene locus on chromosome 8q22. Several of these variants have been demonstrated to have genetic association with lipid level variation but many remain unresolved. Controversial reports on the genetic association of variants among different populations pose a challenge to which variants are informative. This study aimed to investigate “common” LPL variants (rs1121923, rs258, rs328, rs13702) and their possible role in plasma lipid level. Genotyping was performed using Realtime PCR. Based on the observed genotypes, the minor allele frequencies were A: 0.065 for rs1121923; C: 0.379 for rs258; G: 0.087 for rs328 and C: 0.337 for rs13702. Using linear regression, a lowering effect of rs1121923 (p = 0.024) on TG levels (−0.14 B coefficient: CI: −0.27–−0.019) and rs258 (p = 0.013) on VLDL levels (B: −0.046; CI: −0.082–−0.009) was observed indicating a “protective” role for the two variants. Moreover, the findings indicate the potential for including rs1121923 and rs258 in diagnostic panels for use as an estimator of “risk” scores for dyslipidemia.
Anomalous isotope effect in iron-based superconductors
Authors: Huang Wen-Min , Lin Hsiu-Hau 
Published: April 2019

AbstractThe role of electron-phonon interactions in iron-based superconductor is currently under debate with conflicting experimental reports on the isotope effect. To address this important issue, we employ the renormalization-group method to investigate the competition between electron-electron and electron-phonon interactions in these materials. The renormalization-group analysis shows that the ground state is a phonon-dressed unconventional superconductor: the dominant electronic interactions account for pairing mechanism while electron-phonon interactions are subdominant. Because of the phonon dressing, the isotope effect of the critical temperature can be normal or reversed, depending on whether the retarded intra- or inter-band interactions are altered upon isotope substitutions. The connection between the anomalous isotope effect and the unconventional pairing symmetry is discussed at the end.
Towards a rational design of faecal transplant analogues
Authors: Larsen Olaf F. A. , Koning Anton H. J. , van der Spek Peter J. , Claassen Eric 
Published: April 2019

AbstractFaecal transplants (microbiota transfer) have shown to be promising therapies having a wide range of therapeutic applications. However, current safety considerations hamper further valorisation. As such, well designed faecal transplant analogues provide an interesting alternative to minimize possible safety aspects. However, to date little knowledge on how to rationally design such analogues exists. Here, we show by applying first order basic graph theory that such analogues dedicated to restoring a specific physiological functionality (a microbial guild) should consist of 5–6 species to maximize stability, efficiency, and minimize safety issues and production costs.
Choriocapillaris Flow Impairments in Association with Pachyvessel in Early Stages of Pachychoroid
Authors: Baek Jiwon , Kook Lee , Lee Won Ki 
Published: April 2019

AbstractTo analyze features of the choriocapillaris in eyes with earlier stages of pachychoroid spectrum, this study included 46 eyes with PPE, 32 age-matched eyes with pachychoroid without epitheliopathy, and 30 normal controls. Macular 3 × 3 mm2 angiographic images were obtained with swept-source optical coherence tomography. Vascular density and signal void area in the choriocapillaris were analyzed. Topographical correlation of signal voids with the dilated choroidal large vessel (pachyvessel) was assessed. Choriocapillaris vascular density was significantly lower in eyes with PPE compared with controls (p = 0.003). The number, the total area and the average size of signal voids was the highest in the PPE group followed by the pachychoroid without epitheliopathy and then controls (all p ≤ 0.001). 89.0% signal void area colocalized with pachyvessels. The average size of the signal void was higher if it was colocalized with pachyvessel (p < 0.001). In conclusion, the area of flow impairment in the choriocapillaris was increased in eyes with pachychoroid and even greater when epitheliopathy was present. Pachyvessel was associated with choriocapillaris flow impairment by location and size.
HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic
Authors: Cabrera-Rodríguez Romina , Hebmann Veronique , Marfil Silvia , Pernas María , Marrero-Hernández Sara , Cabrera Cecilia , Urrea Victor , Casado Concepción , Olivares Isabel , Márquez-Arce Daniel , Pérez-Yanes Silvia , Estévez-Herrera Judith , Clotet Bonaventura , Espert Lucile , López-Galíndez Cecilio , Biard-Piechaczyk Martine , Valenzuela-Fernández Agustín , Blanco Julià 
Published: April 2019

AbstractIn untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4+ T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype. Full-length Env clones isolated from individuals with Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid progressors (RPs, n = 17) were geno- and phenotypically analyzed by determining diversity, expression, CD4 binding/signaling, fusogenicity, infectivity and autophagy induction. Selected Env clones from VNPs and RPs (n = 32) showed similar expression, fusion and infection abilities. Env clones from both groups showed similar affinity for CD4 during cell-to-cell transmission and consistently induced similar levels of CD4 signaling, measured by α-tubulin acetylation. Moreover, we demonstrate for the first time that primary Env clones from VNP and RP induce autophagy in uninfected cells and that this feature correlated with fusogenic capacity but was unrelated to disease progression. In conclusion, our data suggest that Env clones from VNP individuals are fully functional. Therefore, the paradoxical CD4+ T cell count stability coexisting with high levels of viral replication is unrelated to Env function.
Discovery of novel astrovirus and calicivirus identified in ruddy turnstones in Brazil
Authors: de Souza William Marciel , Fumagalli Marcílio Jorge , de Araujo Jansen , Ometto Tatiana , Modha Sejal , Thomazelli Luciano Matsumiya , Durigon Edison Luís , Murcia Pablo Ramiro , Figueiredo Luiz Tadeu Moraes 
Published: April 2019

AbstractBirds are the natural reservoir of viruses with zoonotic potential, as well as contributing to the evolution, emergence, and dissemination of novel viruses. In this study, we applied a high-throughput screening approach to identify the diversity of viruses in 118 samples of birds captured between October 2006 to October 2010 in the North and Northeast regions of Brazil. We found nearly complete genomes of novel species of astrovirus and calicivirus in cloacal swabs of ruddy turnstones (Arenaria interpres) collected in Coroa do Avião islet, Pernambuco State. These viruses are positive-sense single-stranded RNA with a genome of ~7 to 8 kb, and were designated as Ruddy turnstone astrovirus (RtAstV) and Ruddy turnstone calicivirus (RTCV), respectively. Phylogenetic analysis showed that RtAstV and RTCV grouped in a monophyletic clade with viruses identified from poultry samples (i.e., chicken, goose, and turkey), including viruses associated with acute nephritis in chickens. Attempts of viral propagation in monkey and chicken cell lines for both viruses were unsuccessful. Also, we found genomes related with viral families that infect invertebrates and plants, suggesting that they might be ingested in the birds’ diet. In sum, these findings shed new light on the diversity of viruses in migratory birds with the notable characterization of a novel astrovirus and calicivirus.
Submesoscale ocean fronts act as biological hotspot for southern elephant seal
Authors: Siegelman Lia , O’Toole Malcolm , Flexas Mar , Rivière Pascal , Klein Patrice 
Published: April 2019

AbstractThe area west of the Kerguelen Islands (20–70°E/45–60°S) is characterized by a weak mesoscale activity except for a standing meander region of the Antarctic Circumpolar Current (ACC) localized between 20 and 40°E. A unique bio-physical dataset at high-resolution collected by a southern elephant seal (Mirounga leonina) reveals a conspicuous increase in foraging activity at the standing meander site up to 5 times larger than during the rest of her three-month trip west of the Kerguelen Islands. Here, we propose a physical explanation for such high biological activity based on the study of small-scale fronts with scales of 5 to 20 km, also called submesoscales. The standing meander is associated with intensified frontal dynamics at submesoscale, not observed in the rest of the region. Results shed new light on the spatial distribution of submesoscale fronts in the under-sampled area west of the Kerguelen plateau and emphasize their importance for upper trophic levels. Despite that most elephant seals target foraging grounds east of the Kerguelen Plateau, our findings suggest that excursions to the west are not accidental, and may be explained by the recurrently elevated physical and biological activity of the site. As such, other standing meanders of the ACC may also act as biological hotspots where trophic interactions are stimulated by submesoscale turbulence.
Response kinetics reveal novel features of ageing in murine T cells
Authors: Pieren Daan K. J. , Smits Noortje A. M. , van de Garde Martijn D. B. , Guichelaar Teun 
Published: April 2019

AbstractThe impact of ageing on the immune system results in defects in T cell responsiveness. The search for ageing hallmarks has been challenging due to the complex nature of immune responses in which the kinetics of T cell responsiveness have largely been neglected. We aimed to unravel hallmarks of ageing in the kinetics of the murine T cell response. To this end, we assessed ageing-related T-cell response kinetics by studying the effect of the duration and strength ofin vitrostimulation on activation, proliferation, and cytokine secretion by T cells of young and aged mice. Collectively, our data show that stimulatory strength and time kinetics of cytokine secretion, activation markers, and proliferation of Th, Tc, and Treg cells are crucial in understanding the impact of ageing on T cells. Despite low proliferative capacity, T cell subsets of aged mice do respond to stimulation by upregulation of activation markers and secretion of cytokines. These findings therefore indicate that replicative senescence of aged T cells is not a measure of unresponsiveness per se, but rather stress that ageing influences the kinetics of proliferation, upregulation of activation markers and cytokine secretion each to a different extent.
Glucosamine inhibits IL-1β expression by preserving mitochondrial integrity and disrupting assembly of the NLRP3 inflammasome
Authors: Chiu Hsiao-Wen , Li Lan-Hui , Hsieh Chih-Yu , Rao Yerra Koteswara , Chen Fang-Hsin , Chen Ann , Ka Shuk-Man , Hua Kuo-Feng 
Published: April 2019

AbstractThe NLRP3 inflammasome promotes the pathogenesis of metabolic, neurodegenerative and infectious diseases. Increasing evidences show that the NLRP3 inflammasome is a promising therapeutic target in inflammatory diseases. Glucosamine is widely used as a dietary supplement to promote the health of cartilage tissue and is expected to exert anti-inflammatory activity in joint inflammation, which is a nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome-associated complication. Here, we investigated whether GlcN inhibits the NLRP3 inflammasome and dissected the underlying molecular mechanisms. We found that GlcN suppressed the NLRP3 inflammasome in mouse and human macrophages. A mechanistic study revealed that GlcN inhibited the expression of NLRP3 and IL-1β precursor by reducing reactive oxygen species generation and NF-κB activation in lipopolysaccharide-activated macrophages. GlcN also suppressed mitochondrial reactive oxygen species generation and mitochondrial integrity loss in NLRP3-activated macrophages. Additionally, GlcN disrupted NLRP3 inflammasome assembly by inhibiting NLRP3 binding to PKR, NEK7 and ASC. Furthermore, oral administration of GlcN reduced peritoneal neutrophils influx and lavage fluids concentrations of IL-1β, IL-6 MCP-1 and TNF-α in uric acid crystal-injected mice. These results indicated that GlcN might be a novel dietary supplement for the amelioration of NLRP3 inflammasome-associated complications.
A pan-RAF inhibitor LY3009120 inhibits necroptosis by preventing phosphorylation of RIPK1 and alleviates dextran sulfate sodium-induced colitis
Authors: Zhang Chong , Luo Yiqin , He Qiaoling , Liu Shuai , He Andong , Yan Jie 
Published: April 2019

Abstract
A dramatic increase in the incidence of inflammatory bowel disease (IBD) has been observed in the past two decades, mainly in developed countries and also in developing regions. Necroptosis has been found to play an important role in the pathogenesis of IBD, suggesting its inhibitors are promising in clinic. However, clinical drugs targeting necroptosis are seriously lacking. Through screening a clinical compound library that contains 611 inhibitors, a pan-RAF inhibitor LY3009120 was found to be promising as a necroptosis inhibitor. LY3009120 inhibited necroptosis in vitro, and its inhibition against necroptosis was independent of its well-known activity to inhibit RAF. Surprisingly, LY3009120 prevented phosphorylation of receptor interacting serine/threonine kinase 1 (RIPK1) and subsequently phosphorylation of receptor interacting serine/threonine kinase 3 (RIPK3) and mixed lineage kinase domain like pseudokinase (MLKL) which happened during necroptosis. In vivo, LY3009120 significantly alleviated dextran sulfate sodium (DSS)-induced colitis as indicated by prevention of body weight loss, colon shortening, and decreased mortality. Furthermore, LY3009120 inhibited necroptosis of intestinal epithelial cells (IECs) and prevented intestinal barrier function loss. Consistently, LY3009120 decreased DSS-induced colonic inflammation, as indicated by decreased infiltration of macrophages and neutrophils, and decreased colonic TNF-α, IL-6, and IL-1β level in DSS treated mice. These results indicate that an anti-cancer pan-RAF inhibitor LY3009120 is a necroptosis inhibitor and may serve as a potential therapeutic drug for colitis.
Activity time series of old stars from late F to early K
Authors: Meunier N. , Lagrange A.-M. , Boulet T. , Borgniet S. 
Published: April 2019

Context. Solar simulations and observations show that the detection of long-period Earth-like planets is expected to be very difficult with radial velocity techniques in the solar case because of activity. The inhibition of the convective blueshift in active regions (which is then dominating the signal) is expected to decrease toward lower mass stars, which would provide more suitable conditions.
Aims. In this paper we build synthetic time series to be able to precisely estimate the effects of activity on exoplanet detectability for stars with a wide range of spectral type (F6-K4) and activity levels (old main-sequence stars).
Methods. We simulated a very large number of realistic time series of radial velocity, chromospheric emission, photometry, and astrometry. We built a coherent grid of stellar parameters that covers a wide range in the (B–V, Log R′HK) space based on our current knowledge of stellar activity, to be able to produce these time series. We describe the model and assumptions in detail.
Results. We present first results on chromospheric emission. We find the average Log R′HK to correspond well to the target values that are expected from the model, and observe a strong effect of inclination on the average Log R′HK (over time) and its long-term amplitude.
Conclusions. This very large set of synthetic time series offers many possibilities for future analysis, for example, for the parameter effect, correction method, and detection limits of exoplanets.
Extreme hydrodynamic losses of Earth-like atmospheres in the habitable zones of very active stars
Authors: Johnstone C. P. , Khodachenko M. L. , Lüftinger T. , Kislyakova K. G. , Lammer H. , Güdel M. 
Published: April 2019

Aims. In this Letter, we calculate for the first time the full transonic hydrodynamic escape of an Earth-like atmosphere. We consider the case of an Earth-mass planet with an atmospheric composition identical to that of the current Earth orbiting at 1 AU around a young and very active solar mass star.
Methods. To model the upper atmosphere, we used the Kompot Code, which is a first-principles model that calculates the physical structures of the upper atmospheres of planets, taking into account hydrodynamics and the main chemical and thermal processes taking place in the upper atmosphere of a planet. This model enabled us to calculate the 1D vertical structure of the atmosphere using as input the high-energy spectrum of a young and active Sun.
Results. The atmosphere has the form of a transonic hydrodynamic Parker wind, which has an outflow velocity at the upper boundary of our computational domain that exceeds the escape velocity. The outflowing gas is dominated by atomic nitrogen and oxygen and their ion equivalents and has a maximum ionization fraction of 20%. The mass outflow rate is found to be 1.8 × 109 g s−1, which would erode the modern Earth’s atmosphere in less than 0.1 Myr.
Conclusions. This extreme mass loss rate suggests that an Earth-like atmosphere cannot form when the planet is orbiting within the habitable zone of a very active star. Instead, such an atmosphere can only form after the activity of the star has decreased to a much lower level. This happened in the early atmosphere of the Earth, which was likely dominated by other gases such as CO2. Since the time it takes for the activity of a star to decay is highly dependent on its mass, this is important for understanding possible formation timescales for planets orbiting low-mass stars.