bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LRRC8-mediated volume-regulated anion channel is altered in glaucoma
Authors: Gasull Xavier , Castany Marta , Castellanos Aida , Rezola Mikel , Andrés-Bilbé Alba , Canut Maria Isabel , Estévez Raúl , Borrás Teresa , Comes Núria 
Published: April 2019

AbstractRegulation of cellular volume is an essential process to balance volume changes during cell proliferation and migration or when intracellular osmolality increases due to transepithelial transport. We previously characterized the key role of volume-regulated anion channels (VRAC) in the modulation of the volume of trabecular meshwork (TM) cells and, in turn, the aqueous humour (AH) outflow from the eye. The balance between the secretion and the drainage of AH determines the intraocular pressure (IOP) that is the major casual risk factor for glaucoma. Glaucoma is an ocular disease that causes irreversible blindness due to the degeneration of retinal ganglion cells. The recent identification of Leucine-Rich Repeat-Containing 8 (LRRC8A-E) proteins as the molecular components of VRAC opens the field to elucidate their function in the physiology of TM and glaucoma. Human TM cells derived from non-glaucomatous donors and from open-angle glaucoma patients were used to determine the expression and the functional activity of LRRC8-mediated channels. Expression levels of LRRC8A-E subunits were decreased in HTM glaucomatous cells compared to normotensive HTM cells. Consequently, the activity of VRAC currents and volume regulation of TM cells were significantly affected. Impaired cell volume regulation will likely contribute to altered aqueous outflow and intraocular pressure.
Foraging Experiences Durably Modulate Honey Bees’ Sucrose Responsiveness and Antennal Lobe Biogenic Amine Levels
Authors: Finkelstein Abby Basya , Brent Colin S. , Giurfa Martin , Amdam Gro V. 
Published: April 2019

AbstractForaging exposes organisms to rewarding and aversive events, providing a selective advantage for maximizing the former while minimizing the latter. Honey bees (Apis mellifera) associate environmental stimuli with appetitive or aversive experiences, forming preferences for scents, locations, and visual cues. Preference formation is influenced by inter-individual variation in sensitivity to rewarding and aversive stimuli, which can be modulated by pharmacological manipulation of biogenic amines. We propose that foraging experiences act on biogenic amine pathways to induce enduring changes to stimulus responsiveness. To simulate varied foraging conditions, freely-moving bees were housed in cages where feeders offered combinations of sucrose solution, floral scents, and aversive electric shock. Transient effects were excluded by providing bees with neutral conditions for three days prior to all subsequent assays. Sucrose responsiveness was reduced in bees that had foraged for scented rather than unscented sucrose under benign conditions. This was not the case under aversive foraging conditions, suggesting an adaptive tuning process which maximizes preference for high quality, non-aversive floral sites. Foraging conditions also influenced antennal lobe octopamine and serotonin, neuromodulators involved in stimulus responsiveness and foraging site evaluation. Our results suggest that individuals’ foraging experiences durably modify neurochemistry and shape future foraging behaviour.
Thermally controllable Mie resonances in a water-based metamaterial
Authors: Sun Xiaqing , Fu Quanhong , Fan Yuancheng , Wu Hongjing , Qiu Kepeng , Yang Ruisheng , Cai Weiqi , Zhang Nan , Zhang Fuli 
Published: April 2019

AbstractActive control of metamaterial properties is of great significance for designing miniaturized and versatile devices in practical engineering applications. Taking advantage of the highly temperature-dependent permittivity of water, we demonstrate a water-based metamaterial comprising water cubes with thermally tunable Mie resonances. The dynamic tunability of the water-based metamaterial was investigated via numerical simulations and experiments. A water cube exhibits both magnetic and electric response in the frequency range of interest. The magnetic response is primarily magnetic dipole resonance, while the electric response is a superposition of electric dipole resonance and a smooth Fabry–Pérot background. Using temporal coupled-mode theory (TCMT), the role of direct scattering is evaluated and the Mie resonance modes are analyzed. As the temperature of water cube varies from 20 °C to 80 °C, the magnetic and electric resonance frequencies exhibit obvious blue shifts of 0.10 and 0.14 GHz, respectively.
Garlic augments the functional and nutritional behavior of Doenjang, a traditional Korean fermented soybean paste
Authors: Bahuguna Ashutosh , Shukla Shruti , Lee Jong Suk , Bajpai Vivek K. , Kim So-Young , Huh Yun Suk , Han Young-Kyu , Kim Myunghee 
Published: April 2019

AbstractThree different forms of garlic, namely, fresh garlic (2%, 6%, 10%), heat-dried (1%, 2%, 3%) and freeze-dried (1%, 2%, 3%), were supplemented in soybean paste to prepare Doenjang and further evaluated for functional, nutritional and safety aspects. Results showed a considerable antioxidant and anti-proliferative activity of garlic-supplemented Doenjang. As a measure of nutritive value, a high amount of total free amino acids, 4,290.73 mg/100 g–5,492.94 mg/100 g, was observed in prepared Doenjang. Among all preparations, 3% freeze-dried garlic-supplemented Doenjang proved the most effective against gastric adenocarcinoma and lung adenocarcinoma with 50% inhibition concentration of 7.66 ± 0.53 mg/mL and 7.82 ± 0.34 mg/mL, respectively. However 10% fresh-garlicsupplemented Doenjang (GGD-10) showed better activity against colorectal adenocarcinoma (HT29) cell line. Furthermore, GGD-10 effectively reduced colony formation and altered mitochondrial membrane potential of HT29 cells. Absence of pathogenic bacteria (Staphylococcus aureus, Salmonella species and Bacillus cereus) and aflatoxin was observed in Doenjang samples. In addition, nontoxic amount of anti-nutritional biogenic amines was observed in all the samples. The results collectively suggest that the addition of garlic in Doenjang can improve its nutritional and functional value, resulting in the protection of consumers from protein deficiencies and various stress conditions.
The Rice Phosphate Transporter Protein OsPT8 Regulates Disease Resistance and Plant Growth
Authors: Dong Zheng , Li Wei , Liu Jing , Li Lihua , Pan Sujun , Liu Saijun , Gao Jia , Liu Ling , Liu Xionglun , Wang Guo-Liang , Dai Liangying 
Published: April 2019

AbstractThe absorption of nutrients and disease resistance are two indispensable physiological processes in plants; however, it is still largely unknown whether there is cross-talk between their molecular signaling pathways. In this study, we identified the rice OsPT8 protein, which is a member of the phosphate transporters (PTs) Pht1 family and also plays a role in rice disease resistance. The transcriptional level of OsPT8 is suppressed after infection with rice pathogens and treatment with pathogen-associated molecular patterns (PAMPs). Overexpression of OsPT8 suppresses rice disease resistance against the pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae. Accordingly, the transcription level of resistance related genes, such as PAL and PBZ1, is inhibited in plants overexpressing OsPT8 (OsPT8-OX) after inoculation with these pathogens. In OsPT8-OX plants, PAMPs-triggered immunity (PTI) response genes, such as OsRac1 and SGT1, are suppressed during treatment with PAMPs chitin or flg22. Moreover, the typical response of PTI is suppressed after chitin or flg22 treatment. We also identified OsPT8 as an interactor of a rice mitogen-activated protein kinase BWMK1, which is a regulator of disease resistance. Under low phosphate (Pi) conditions, the OsPT8-OX plants display better agronomic traits than the control plants. However, the differences in development between OsPT8-OX and the control plants are reduced upon the increase of Pi concentration. These results demonstrate that OsPT8 regulates the transduction of Pi signaling for development and negatively regulates rice immunity.
Prognostic Value of CT Radiomic Features in Resectable Pancreatic Ductal Adenocarcinoma
Authors: Khalvati Farzad , Zhang Yucheng , Baig Sameer , Lobo-Mueller Edrise M. , Karanicolas Paul , Gallinger Steven , Haider Masoom A. 
Published: April 2019

AbstractIn this work, we assess the reproducibility and prognostic value of CT-derived radiomic features for resectable pancreatic ductal adenocarcinoma (PDAC). Two radiologists contoured tumour regions on pre-operative CT of two cohorts from two institutions undergoing curative-intent surgical resection for PDAC. The first (n = 30) and second cohorts (n = 68) were used for training and validation of proposed prognostic model for overall survival (OS), respectively. Radiomic features were extracted using PyRadiomics library and those with weak inter-reader reproducibility were excluded. Through Cox regression models, significant features were identified in the training cohort and retested in the validation cohort. Significant features were then fused via Cox regression to build a single radiomic signature in the training cohort, which was validated across readers in the validation cohort. Two radiomic features derived from Sum Entropy and Cluster Tendency features were both robust to inter-reader reproducibility and prognostic of OS across cohorts and readers. The radiomic signature showed prognostic value for OS in the validation cohort with hazard ratios of 1.56 (P = 0.005) and 1.35 (P = 0.022), for the first and second reader, respectively. CT-based radiomic features were shown to be prognostic in patients with resectable PDAC. These features may help stratify patients for neoadjuvant or alternative therapies.
Chiral phenoxyacetic acid analogues inhibit colon cancer cell proliferation acting as PPARγ partial agonists
Authors: Sabatino Lina , Ziccardi Pamela , Cerchia Carmen , Muccillo Livio , Piemontese Luca , Loiodice Fulvio , Colantuoni Vittorio , Lupo Angelo , Lavecchia Antonio 
Published: April 2019

AbstractPeroxisome Proliferator-Activated Receptor γ (PPARγ) is an important sensor at the crossroad of diabetes, obesity, immunity and cancer as it regulates adipogenesis, metabolism, inflammation and proliferation. PPARγ exerts its pleiotropic functions upon binding of natural or synthetic ligands. The molecular mechanisms through which PPARγ controls cancer initiation/progression depend on the different mode of binding of distinctive ligands. Here, we analyzed a series of chiral phenoxyacetic acid analogues for their ability to inhibit colorectal cancer (CRC) cells growth by binding PPARγ as partial agonists as assessed in transactivation assays of a PPARG-reporter gene. We further investigated compounds (R,S)-3, (S)-3 and (R,S)-7 because they combine the best antiproliferative activity and a limited transactivation potential and found that they induce cell cycle arrest mainly via upregulation of p21waf1/cip1. Interestingly, they also counteract the β-catenin/TCF pathway by repressing c-Myc and cyclin D1, supporting their antiproliferative effect. Docking experiments provided insight into the binding mode of the most active compound (S)-3, suggesting that its partial agonism could be related to a better stabilization of H3 rather than H11 and H12. In conclusion, we identified a series of PPARγ partial agonists affecting distinct pathways all leading to strong antiproliferative effects. These findings may pave the way for novel therapeutic strategies in CRC.
Oxygen/phosphorus co-doped porous carbon from cicada slough as high-performance electrode material for supercapacitors
Authors: Chen Bingwei , Wu Wenzhuo , Li Chunyang , Wang Yanfang , Zhang Yi , Fu Lijun , Zhu Yusong , Zhang Lixin , Wu Yuping 
Published: April 2019

AbstractSynthesizing high-performance electrode materials plays a vital role in fabricating advanced supercapacitors. Heteroatom doping has been proved to be effective in enhancing the electrochemical properties of carbon-based electrodes. Herein, we report an O, P co-doped porous carbon (PC) originated from waste biomaterials, cicada sloughs. The PC possesses meso-/microporous structure with a large specific surface area (1945 m2·g−1) and a high O, P co-doping ratio of 18 wt.%. These superior factors together enable it to deliver high specific capacitance (295 F·g−1 in 6 M KOH and 291 F·g−1 in 1 M H2SO4), good cycling stability (100% capacitance retention after 10000 cycles in 1 M H2SO4) and rate performance. Therefore, from the respects of environment friendliness and cost effectivity, obtaining heteroatom doped carbons from the nature might be better compared to pyrolyzing heteroatom-containing chemicals.
Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer
Authors: Ozeki Tomoko , Nagahama Mitsuji , Fujita Kazuma , Suzuki Akifumi , Sugino Kiminori , Ito Koichi , Miura Masatomo 
Published: April 2019

AbstractLenvatinib is a substrate of cytochrome P450 (CYP) 3A and ATP-binding cassette (ABC) transporters. In this study, we aimed to evaluate how CYP3A4/5 and ABC transporter polymorphisms affected the mean steady-state dose-adjusted plasma trough concentrations (C0) of lenvatinib in a cohort of 40 Japanese patients with thyroid cancer. CYP3A4 20230G > A (*1G), CYP3A5 6986A > G (*3), ABCB1 1236C > T, ABCB1 2677G > T/A, ABCB1 3435C > T, ABCC2 −24C > T, and ABCG2 421C > A genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. In univariate analysis, there were no significant differences in the mean dose-adjusted C0 values of lenvatinib between the ABCB1, ABCG2, and CYP3A5 genotypes. However, the mean dose-adjusted C0 values of lenvatinib in patients with the CYP3A4*1/*1 genotype and ABCC2 −24T allele were significantly higher than those in patients with the CYP3A4*1G allele and −24C/C genotype, respectively (P = 0.018 and 0.036, respectively). In multivariate analysis, CYP3A4 genotype and total bilirubin were independent factors influencing the dose-adjusted C0 of lenvatinib (P = 0.010 and 0.046, respectively). No significant differences were found in the incidence rates of hypertension, proteinuria, and hand-foot syndrome following treatment with lenvatinib between the genotypes of CYP3A4/5 and ABC transporters. Lenvatinib pharmacokinetics were significantly influenced by the CYP3A4*1G polymorphism. If the target plasma concentration of lenvatinib for efficacy or toxicity is determined, elucidation of the details of the CYP3A4*1G genotype may facilitate decision-making related to the appropriate initial lenvatinib dosage to achieve optimal plasma concentrations.
Identifying Rare Variant Associations in Admixed Populations
Authors: Qin Huaizhen , Zhao Jinying , Zhu Xiaofeng 
Published: April 2019

AbstractAn admixed population and its ancestral populations bear different burdens of a complex disease. The ancestral populations may have different haplotypes of deleterious alleles and thus ancestry-gene interaction can influence disease risk in the admixed population. Among admixed individuals, deleterious haplotypes and their ancestries are dependent and can provide non-redundant association information. Herein we propose a local ancestry boosted sum test (LABST) for identifying chromosomal blocks that harbor rare variants but have no ancestry switches. For such a stable ancestral block, our LABST exploits ancestry-gene interaction and the number of rare alleles therein. Under the null of no genetic association, the test statistic asymptotically follows a chi-square distribution with one degree of freedom (1-df). Our LABST properly controlled type I error rates under extensive simulations, suggesting that the asymptotic approximation was accurate for the null distribution of the test statistic. In terms of power for identifying rare variant associations, our LABST uniformly outperformed several famed methods under four important modes of disease genetics over a large range of relative risks. In conclusion, exploiting ancestry-gene interaction can boost statistical power for rare variant association mapping in admixed populations.
miR-21-mediated regulation of 15-hydroxyprostaglandin dehydrogenase in colon cancer
Authors: Monteleone Nicholas J. , Moore Ashleigh E. , Iacona Joseph R. , Lutz Carol S. , Dixon Dan A. 
Published: April 2019

AbstractElevated prostaglandin E2 (PGE2) levels are observed in colorectal cancer (CRC) patients, and this increase is associated with poor prognosis. Increased synthesis of PGE2 in CRC has been shown to occur through COX-2-dependent mechanisms; however, loss of the PGE2-catabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, HPGD), in colonic tumors contributes to increased prostaglandin levels and poor patient survival. While loss of 15-PGDH can occur through transcriptional mechanisms, we demonstrate that 15-PGDH can be additionally regulated by a miRNA-mediated mechanism. We show that 15-PGDH and miR-21 are inversely correlated in CRC patients, with increased miR-21 levels associating with low 15-PGDH expression. 15-PGDH can be directly regulated by miR-21 through distinct sites in its 3′ untranslated region (3′UTR), and miR-21 expression in CRC cells attenuates 15-PGDH and promotes increased PGE2 levels. Additionally, epithelial growth factor (EGF) signaling suppresses 15-PGDH expression while simultaneously enhancing miR-21 levels. miR-21 inhibition represses CRC cell proliferation, which is enhanced with EGF receptor (EGFR) inhibition. These findings present a novel regulatory mechanism of 15-PGDH by miR-21, and how dysregulated expression of miR-21 may contribute to loss of 15-PGDH expression and promote CRC progression via increased accumulation of PGE2.
Madden–Julian Oscillation Enhances Phytoplankton Biomass in the Maritime Continent
Authors: Chang Chiung-Wen June , Hsu Huang-Hsiung , Cheah Wee , Tseng Wan-Ling , Jiang Li-Chiang 
Published: April 2019

AbstractIn addition to monsoon-driven rainfall, the Maritime Continent (MC) is subject to heavy precipitation caused by the Madden–Julian Oscillation (MJO), a tropical convection-coupled circulation that propagates eastward from the Indian to the Pacific Ocean. This study shows that riverine runoff from MJO-driven rainfall in the western MC significantly enhances phytoplankton biomass not only in the coastal regions but as far as the nutrient-poor Banda Sea, located 1,000 km downstream of the riverine source. We present observational estimates of the chlorophyll-a concentration in the Banda Sea increasing by 20% over the winter average within an MJO life cycle. The enhancement of phytoplankton in the central Banda Sea is attributed to two coinciding MJO-triggered mechanisms: enhanced sediment loading and eastward advection of waters with high sediment and chlorophyll concentrations. Our results highlight an unexpected effect of MJO-driven rainfall on the downstream oceanic region. This finding has significant implications for the marine food chain and biogeochemical processes in the MC, given the increasing deforestation rate and projections that global warming will intensify both the frequency and strength of MJO-driven rainfall in the MC.
Fabrication of inclined non-symmetrical periodic micro-structures using Direct Laser Interference Patterning
Authors: Alamri Sabri , El-Khoury Mikhael , Aguilar-Morales Alfredo I. , Storm Sebastian , Kunze Tim , Lasagni Andrés F. 
Published: April 2019

AbstractThe direct fabrication of microstructures, having a non-symmetrical morphology with controllable inclination, presents nowadays a challenging task. Natural examples of surfaces with inclined topographies have shown to provide anisotropic functionalities, which have attracted the interest of several researchers in the last years. This work presents a microfabrication technique for producing microstructures with a determined and controllable inclination angle using two-beam Direct Laser Interference Patterning. Polyimide foils are irradiated with a 4 ns UV (266 nm) laser source producing line-like structures with a period varying from 4.6 µm to 16.5 µm. The inclinations, retrieved by tilting the sample with respect to the optical axis of the setup, are changed from 0° to 75°, introducing a well controllable and defined inclination of the structure walls. The structuring parameters (laser fluence, number of laser pulses and interference period) as well as the inclination of the microstructures are correlated with the global tilting of the sample. As a result, a determined laser fluence and number of pulses are necessary to observe a remarkable non-symmetrical morphology of the structures. In addition, the presence of structural undercuts is reported, which opens the possibility for developing new direction-dependent properties on polymeric materials. As an example, preliminary results on light diffraction are presented, showing a similar behavior as blazed diffraction gratings.
Switchable multifunctional terahertz metasurfaces employing vanadium dioxide
Authors: Li Xike , Tang Shiwei , Ding Fei , Zhong Shuomin , Yang Yuanqing , Jiang Tao , Zhou Jun 
Published: April 2019

AbstractIn this paper, we design a type of switchable metasurfaces by employing vanadium dioxide (VO2), which possess tunable and diversified functionalities in the terahertz (THz) frequencies. The properly designed homogeneous metasurface can be dynamically tuned from a broadband absorber to a reflecting surface due to the insulator-to-metal transition of VO2. When VO2 is in its insulating state, the metasurface can efficiently absorb the normally incident THz wave in the frequency range of 0.535–1.3 THz with the average absorption of ~97.2%. Once the VO2 is heated up and switched to its fully metallic state, the designed metasurface exhibits broadband and efficient reflection (>80%) in the frequency range from 0.5 to 1.3 THz. Capitalizing on such meta-atom design, we further extend the functionalities by introducing phase-gradients when VO2 is in its fully metallic state and consequently achieve polarization-insensitive beam-steering and polarization-splitting, while maintaining broadband absorption when VO2 is in insulating state.
Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response
Authors: Rosina M. , Langone F. , Giuliani G. , Cerquone Perpetuini A. , Reggio A. , Calderone A. , Fuoco C. , Castagnoli L. , Gargioli C. , Cesareni G. 
Published: April 2019

AbstractHeterotopic ossification (HO) is a pathological condition characterized by the deposition of mineralized tissue in ectopic locations such as the skeletal muscle. The precise cellular origin and molecular mechanisms underlying HO are still debated. In our study we focus on the differentiation of mesoangioblasts (MABs), a population of multipotent skeletal muscle precursors. High-content screening for small molecules that perturb MAB differentiation decisions identified Idoxuridine (IdU), an antiviral and radiotherapy adjuvant, as a molecule that promotes MAB osteogenic differentiation while inhibiting myogenesis. IdU-dependent osteogenesis does not rely on the canonical BMP-2/SMADs osteogenic pathway. At pro-osteogenic conditions IdU induces a mild DNA Damage Response (DDR) that activates ATM and p38 eventually promoting the phosphorylation of the osteogenesis master regulator RUNX2. By interfering with this pathway IdU-induced osteogenesis is severely impaired. Overall, our study suggests that induction of the DDR promotes osteogenesis in muscle resident MABs thereby offering a new mechanism that may be involved in the ectopic deposition of mineralized tissue in the muscle.