bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in gene expression in brain structures related to visceral sensation, autonomic functions, food intake, and cognition in melanoma‐bearing mice
Authors: Horvathova Lubica , Tillinger Andrej , Padova Alexandra , Bizik Jozef , Mravec Boris 
Published: December 2019

AbstractThe brain exerts complex effects on the initiation and progression of cancer in the body. However, the influence of cancer localized in peripheral tissues on the brain has been only partially described. Therefore, we investigated gene expression in brain structures that participate in transmitting viscerosensory signals, regulating autonomic functions and food intake, as well as cognition in C57Bl/6J mice with B16‐F10 melanoma. In addition, we investigated the relationship between peripheral inflammation and neuroinflammation. We found increased neuronal activity in the nucleus of the solitary tract of tumor‐bearing mice, whereas neuronal activity in the A1/C1 catecholaminergic cell group, parabrachial nucleus, lateral hypothalamic area, ventromedial nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, and hippocampus was decreased. In the majority of investigated brain structures, we found increased gene expression of IL‐1β, whereas gene expression of IL‐6 and NF‐κB was reduced or unchanged compared with controls. Melanoma‐bearing mice also showed increased gene expression of tyrosine hydroxylase in the A1/C1 catecholaminergic cell group, nucleus of the solitary tract, and locus coeruleus, as well as reduced mRNA levels of hypocretin neuropeptide precursor protein in the lateral hypothalamic area, and proopiomelanocortin in the arcuate nucleus. In addition, we found reduced mRNA levels of Bcl‐2, brain‐derived neurotrophic factor, and doublecortin in the hippocampus. Our data indicate that skin melanoma induces complex changes in the brain, and these changes are most probably caused by cancer‐related signals mediated by pro‐inflammatory cytokines.
Neuroprotective effects of brain‐derived neurotrophic factor against amyloid beta 1‐40‐induced retinal and optic nerve damage
Authors: Mohd Lazaldin Mohd Aizuddin , Iezhitsa Igor , Agarwal Renu , Bakar Nor Salmah , Agarwal Puneet , Mohd Ismail Nafeeza 
Published: December 2019

AbstractBrain‐derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aβ)‐associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aβ1‐40‐induced retinal and optic nerve injury. In this study, exposure to Aβ1‐40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF‐treated group compared with Aβ1‐40 group. H&E‐stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aβ1‐40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF‐treated animals. After Aβ1‐40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF‐treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aβ was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF‐treated than in Aβ1‐40‐treated rats. Both visual object recognition tests using an open‐field arena and a Morris water maze showed that BDNF improved rats’ ability to recognise visual cues (objects with different shapes) after Aβ1‐40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aβ1‐40‐induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.
Ensembling crowdsourced seizure prediction algorithms using long‐term human intracranial EEG
Authors: Reuben Chip , Karoly Philippa , Freestone Dean R. , Temko Andriy , Barachant Alexandre , Li Feng , Titericz Gilberto , Lang Brian W. , Lavery Daniel , Roman Kelly , Broadhead Derek , Jones Gareth , Tang Qingnan , Ivanenko Irina , Panichev Oleg , Proix Timothée , Náhlík Michal , Grunberg Daniel B. , Grayden David B. , Cook Mark J. , Kuhlmann Levin 
Published: December 2019

AbstractSeizure prediction is feasible, but greater accuracy is needed to make seizure prediction clinically viable across a large group of patients. Recent work crowdsourced state‐of‐the‐art prediction algorithms in a worldwide competition, yielding improvements in seizure prediction performance for patients whose seizures were previously found hard to anticipate. The aim of the current analysis was to explore potential performance improvements using an ensemble of the top competition algorithms. The results suggest that minor increments in performance may be possible; however, the outcomes of statistical testing limit the confidence in these increments. Our results suggest that for the specific algorithms, evaluation framework, and data considered here, incremental improvements are achievable but there may be upper bounds on machine learning–based seizure prediction performance for some patients whose seizures are challenging to predict. Other more tailored approaches that, for example, take into account a deeper understanding of preictal mechanisms, patient‐specific sleep‐wake rhythms, or novel measurement approaches, may still offer further gains for these types of patients.
A simplified neutrosophic multiplicative set‐based TODIM using water‐filling algorithm for the determination of weights
Authors: Köseoğlu Ali , Şahin Rıdvan , Merdan Mehmet 
Published: December 2019

AbstractDue to the technological developments around the world, the amount of information that researchers work on increases continuously. This information density contains incomplete and uncertain data that cannot be fully expressed with crisp numbers. Fuzzy sets, intuitionistic fuzzy sets, and neutrosophic sets are useful tools to manage such information, but these concepts use a symmetrical and uniform scale to express data, whereas real‐life problems contain nonsymmetrical and non‐uniform information. Intuitionistic multiplicative sets (IMSs) are effective tools for dealing with these real‐life problems. However, IMSs cannot handle real‐life problems completely because indeterminate information depends on membership and non‐membership information of IMSs, which is a restriction for decision makers and also for decision problems. To overcome this limitation, this paper generalizes the IMSs by using simplified neutrosophic set and introduces a novel approach that is called simplified neutrosophic multiplicative sets (SNMSs). Firstly, we define SNMS, show their set‐based operations, and then give a description of simplified neutrosophic multiplicative numbers (SNMNs). Based on SNMNs, we develop two simplified neutrosophic multiplicative aggregation operators on SNMNs that are called simplified neutrosophic multiplicative weighted arithmetic average operator and simplified neutrosophic multiplicative weighted geometric average operator. Furthermore, we define some simplified neutrosophic multiplicative distance measures. Finally, using a model based on water‐filling algorithm for determining criteria weights, we give a numerical example to demonstrate the effectiveness of the introduced concept with the proposed simplified neutrosophic multiplicative simplified neutrosophic multiplicative‐TODIM method.
Abundance and distribution of the white shark in the Mediterranean Sea
Authors: Moro Stefano , Jona‐Lasinio Giovanna , Block Barbara , Micheli Fiorenza , De Leo Giulio , Serena Fabrizio , Bottaro Massimiliano , Scacco Umberto , Ferretti Francesco 
Published: December 2019

AbstractConservation of apex predators is a key challenge both in marine and terrestrial ecosystems. The white shark is a rare but persistent inhabitant of the Mediterranean Sea and it is currently assessed as “critically endangered” in the region. However, the population trends and dynamics of this species in the area are still unknown. Little is known about white shark distribution, habitat use and population abundance trends, aspects that are critical for conservation and management. In this study, we built the most comprehensive database of white shark occurrence records in the region. We collected 773 different records from different sources and used them to characterize the spatial and temporal patterns of abundance of Mediterranean white sharks between 1860 and 2016. We analysed these data by using generalized additive models and used spatially disaggregated information on human population abundance as a proxy of observation effort. Our results suggest a complex trajectory of population change characterized by a historical increase and a more recent reduction (61%, range 58%–72%) since the second half of the 20th century. In particular, analyses reveal a 52% (range 37%–88%) to 96% (range 92%–100%) overall decline in different Mediterranean sectors and a contraction in spatial distribution. Here, we provide the first reconstruction of abundance trends and offer new hypotheses regarding the drivers of change of white sharks in the Mediterranean. Our approach can be broadly applied to data‐poor contexts to reconstruct change and inform the conservation of endangered top predators in the Mediterranean Sea and other intensely used marine regions.
High affinity of 4‐(4‐(dimethylamino)styryl)‐N‐methylpyridinium transport for assessing organic cation drugs in hepatocellular carcinoma cells
Authors: Jinakote Metee , Ontawong Atcharaporn , Soodvilai Sunhapas , Pimta Jeerawat , Pasachan Tipthida , Chatsudthipong Varanuj , Srimaroeng Chutima 
Published: December 2019

AbstractHuman organic cation transporter 1 (hOCT1) and human organic cation transporter 3 (hOCT3) are highly expressed in hepatocytes and play important roles in cationic drug absorption, distribution, and elimination. A previous study demonstrated that downregulation of hOCT1 and hOCT3 mRNA was related to hepatocellular carcinoma (HepG2) prognosis and severity. Whether these transporters expressed in HepG2 cells serve for cationic drug delivery has not been investigated. Besides radioactive transport, options for assessing hOCTs in hepatocytes are limited. This study clarified the significant roles of hOCTs in HepG2 by comparing cationic fluorescent 4‐(4‐(dimethylamino)styryl)‐N‐methylpyridinium (ASP+) with traditional [3H]‐1‐methyl‐4‐phenylpyridinium (MPP+). The results showed ASP+ was preferably transported into HepG2 compared to [3H]‐MPP+ with high affinity and a high maximal transport rate. Selective transport of ASP+ mediated by hOCTs was influenced by extracellular pH, temperature, and membrane depolarization, corresponding to hOCT1 and hOCT3 expressions. Furthermore, transport of cationic drugs, metformin, and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions. The fluorescent ASP+‐based in vitro model may also provide a rapid and powerful analytical tool for further screening of cationic drug actions and interactions with hOCTs, particularly hOCT1 and hOCT3 in hepatocellular carcinoma.
The structure of Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase‐dihydropteroate synthase reveals the basis of sulfa resistance
Authors: Chitnumsub Penchit , Jaruwat Aritsara , Talawanich Yuwadee , Noytanom Krittikar , Liwnaree Benjamas , Poen Sinothai , Yuthavong Yongyuth 
Published: December 2019

The clinical efficacy of sulfa drugs as antimalarials has declined owing to the evolution of resistance in Plasmodium falciparum (Pf) malaria parasites. In order to understand the basis of this resistance and to design more effective antimalarials, we have solved 13 structures of the bifunctional enzyme 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphokinase (HPPK)–dihydropteroate synthase (DHPS) from wild‐type (WT) P. falciparum and sulfa‐resistant mutants, both as apoenzyme and as complexes with pteroate (PTA) and sulfa derivatives. The structures of these complexes show that PTA, which effectively inhibits both the WT and mutants, stays in active sites without steric constraint. In contrast, parts of the sulfa compounds situated outside of the substrate envelope are in the vicinity of the resistance mutations. Steric conflict between compound and mutant residue along with increased flexibility of loop D2 in the mutants can account for the reduced compound binding affinity to the mutants. Kinetic data show that the mutants have enhanced enzyme activity compared with the WT. These PfDHPS structural insights are critical for the design of novel, substrate envelope–compliant DHPS inhibitors that are less vulnerable to resistance mutations.DatabasesThe data reported in this paper have been deposited in the Protein Data Bank, www.wwpdb.org. PDB ID codes: 6JWQ for apoWT; 6JWR, 6JWS, and 6JWT for PTA complexes of WT, A437G (3D7), and V1/S; 6JWU, 6JWV, and 6JWW for STZ‐DHP complexes of WT, 3D7, and V1/S; 6JWX, 6JWY, and 6JWZ for SDX‐DHP complexes of WT, 3D7, and W2; 6KCK, 6KCL, and 6KCM for Pterin/pHBA complexes of WT, TN1, and W2.
Environment outweighs the effects of fishing in regulating demersal community structure in an exploited marine ecosystem
Authors: Mérillet Laurène , Kopp Dorothée , Robert Marianne , Mouchet Maud , Pavoine Sandrine 
Published: December 2019

AbstractGlobal climate change has already caused bottom temperatures of coastal marine ecosystems to increase worldwide. These ecosystems face many pressures, of which fishing is one of the most important. While consequences of global warming on commercial species are studied extensively, the importance of the increase in bottom temperature and of variation in fishing effort is more rarely considered together in these exploited ecosystems. Using a 17 year time series from an international bottom trawl survey, we investigated covariations of an entire demersal ecosystem (101 taxa) with the environment in the Celtic Sea. Our results showed that over the past two decades, biotic communities in the Celtic Sea were likely controlled more by environmental variables than fisheries, probably due to its long history of exploitation. At the scale of the entire zone, relations between taxa and the environment remained stable over the years, but at a local scale, in the center of the Celtic Sea, dynamics were probably driven by interannual variation in temperature. Fishing was an important factor structuring species assemblages at the beginning of the time series (2000) but decreased in importance after 2009. This was most likely caused by a change in spatial distribution of fishing effort, following a change in targeted taxa from nephrops to deeper water anglerfish that did not covary with fishing effort. Increasing bottom temperatures could induce additional changes in the coming years, notably in the cold‐water commercial species cod, hake, nephrops, and American plaice. We showed that analyzing covariation is an effective way to screen a large number of taxa and highlight those that may be most susceptible to future simultaneous increases in temperature and changes in exploitation pattern by fisheries. This information can be particularly relevant for ecosystem assessments.
Extreme temperature events will drive coral decline in the Coral Triangle
Authors: McManus Lisa C. , Vasconcelos Vítor V. , Levin Simon A. , Thompson Diane M. , Kleypas Joan A. , Castruccio Frederic S. , Curchitser Enrique N. , Watson James R. 
Published: December 2019

AbstractIn light of rapid environmental change, quantifying the contribution of regional‐ and local‐scale drivers of coral persistence is necessary to characterize fully the resilience of coral reef systems. To assess multiscale responses to thermal perturbation of corals in the Coral Triangle (CT), we developed a spatially explicit metacommunity model with coral–algal competition, including seasonal larval dispersal and external spatiotemporal forcing. We tested coral sensitivity in 2,083 reefs across the CT region and surrounding areas under potential future temperature regimes, with and without interannual climate variability, exploring a range of 0.5–2.0°C overall increase in temperature in the system by 2054. We found that among future projections, reef survival probability and mean percent coral cover over time were largely determined by the presence or absence of interannual sea surface temperature (SST) extremes as well as absolute temperature increase. Overall, reefs that experienced SST time series that were filtered to remove interannual variability had approximately double the chance of survival than reefs subjected to unfiltered SST. By the end of the forecast period, the inclusion of thermal anomalies was equivalent to an increase of at least 0.5°C in SST projections without anomalies. Change in percent coral cover varied widely across the region within temperature scenarios, with some reefs experiencing local extinction while others remaining relatively unchanged. Sink strength and current thermal stress threshold were found to be significant drivers of these patterns, highlighting the importance of processes that underlie larval connectivity and bleaching sensitivity in coral networks.
Autumn growth of three perennial weeds at high latitude benefits from climate change
Authors: Tørresen Kirsten S. , Fykse Haldor , Rafoss Trond , Gerowitt Bärbel 
Published: December 2019

AbstractIn autumn, agricultural perennial weeds prepare for winter and can store reserves into creeping roots or rhizomes. Little is known about influence of climate change in this period. We tested the effect of simulated climate change in autumn on three widespread and noxious perennial weeds, Elymus repens (L.) Gould, Cirsium arvense (L.) Scop. and Sonchus arvensis L. We divided and combined simulated climate change components into elevated CO2 concentration (525 ppm), elevated temperatures (+2–2.5°C), treatments in open‐top chambers. In addition, a control in the open‐top chamber without any increase in CO2 and temperature, and a field control outside the chambers were included. Two geographically different origins and three pre‐growth periods prior to the exposure to climate change factors were included for each species. All species increased leaf area under elevated temperature, close to doubling in E. repens and quadrupling in the dicot species. E. repens kept leaves green later in autumn. C. arvense did not benefit in below‐ground growth from more leaf area or leaf dry mass. S. arvensis had low levels of leaf area throughout the experiment and withered earlier than the two other species. Below‐ground plant parts of S. arvensis were significantly increased by elevated temperature. Except for root:shoot ratio of C. arvense, the effects of pure elevated CO2 were not significant for any variables compared to the open‐top chamber control. There was an additive, but no synergistic, effect of enhanced temperature and CO2. The length of pre‐growth period was highly important for autumn plant growth, while origin had minor effect. We conclude that the small transfer of enhanced above‐ground growth into below‐ground growth under climate change in autumn does not favour creeping perennial plants per se, but more leaf area may offer more plant biomass to be tackled by chemical or physical weed control.
Annual ecosystem respiration is resistant to changes in freeze–thaw periods in semi‐arid permafrost
Authors: Wang Qi , Lv Wangwang , Li Bowen , Zhou Yang , Jiang Lili , Piao Shilong , Wang Yanfen , Zhang Lirong , Meng Fandong , Liu Peipei , Hong Huan , Li Yaoming , Dorji Tsechoe , Luo Caiyun , Zhang Zhenhua , Ciais Philippe , Peñuelas Josep , Kardol Paul , Zhou Huakun , Wang Shiping 
Published: December 2019

AbstractWarming in cold regions alters freezing and thawing (F–T) of soil in winter, exposing soil organic carbon to decomposition. Carbon‐rich permafrost is expected to release more CO2 to the atmosphere through ecosystem respiration (Re) under future climate scenarios. However, the mechanisms of the responses of freeze–thaw periods to climate change and their coupling with Re in situ are poorly understood. Here, using 2 years of continuous data, we test how changes in F–T events relate to annual Re under four warming levels and precipitation addition in a semi‐arid grassland with discontinuous alpine permafrost. Warming shortened the entire F–T period because the frozen period shortened more than the extended freezing period. It decreased total Re during the F–T period mainly due to decrease in mean Re rate. However, warming did not alter annual Re because of reduced soil water content and the small contribution of total Re during the F–T period to annual Re. Although there were no effects of precipitation addition alone or interactions with warming on F–T events, precipitation addition increased total Re during the F–T period and the whole year. This decoupling between changes in soil freeze–thaw events and annual Re could result from their different driving factors. Our results suggest that annual Re could be mainly determined by soil water content rather than by change in freeze–thaw periods induced by warming in semi‐arid alpine permafrost.
A Dual Delineation Approach to Untangle Interferences in Well Doublets Systems
Authors: Sbai Mohammed Adil 
Published: December 2019

AbstractTraditional numerical methods for the delineation of wellhead protection areas span deterministic and probabilistic approaches. They provide time‐related capture zones. However, none of the existing approaches identifies the groundwater contribution areas related to each source or sink. In this work, the worthiness of the so‐called double delineation approach was extended. This task was achieved by simple postprocessing of its dual outputs leading to a highly efficient screening tool. In the particular context of geothermal resources management through the well doublets of the Dogger aquifer in the Paris Basin (France), the approach was extended to forecast the compositional heat breakthrough at production wells. Hence, cold‐water breakthrough and temperature decline in production wells are timely assessed in low‐enthalpy geothermal reservoirs. The method quantifies how groundwater volumes are moving through space and time between any couple of source and sink. It provides unprecedented tools advancing the enhanced understanding of water resources systems functioning. It is highly recommended to implement the presented concepts in the current and future generations of community groundwater models.