bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Potentially Potent Heme Oxygenase 1 Inhibitors through 3D‐QSAR Coupled to Scaffold‐Hopping Analysis
Authors: Floresta Giuseppe , Amata Emanuele , Dichiara Maria , Marrazzo Agostino , Salerno Loredana , Romeo Giuseppe , Prezzavento Orazio , Pittalà Valeria , Rescifina Antonio 
Published: April 2018

AbstractA 3D quantitative structure–activity relationship (3D‐QSAR) model for predicting the activity of heme oxygenase 1 (HO‐1) inhibitors was constructed with the aim of providing a useful tool for the identification, design, and optimization of novel HO‐1 inhibitors. The model was built using a set of 222 HO‐1 inhibitors recovered from the Heme Oxygenase Database (HemeOxDB) and developed with the software Forge. The present model showed high statistical quality, as confirmed by its robust predictive potential and satisfactory descriptive capability. The drawn‐up 3D map enables prompt visual comprehension of the electrostatic, hydrophobic, and shaping features underlying the interactions with HO‐1 inhibitors. A theoretical approach for the generation of new lead compounds was performed by means of scaffold‐hopping analysis. For the first time, a 3D‐QSAR model is reported for this target, and was built with a number of chemically diverse HO‐1 inhibitors; the model also accounts well for individual ligand affinities. The new model contains all of the inhibitors published to date with high potency toward the selected target and contains a complete pharmacophore description of the binding cavity of HO‐1. These features will ensure application in accelerating the identification of new potent and selective HO‐1 inhibitors.
Pharmacokinetic Interaction Between Fingolimod and Carbamazepine in Healthy Subjects
Authors: David Olivier J. , Behrje Rhett , Pal Parasar , Hara Hisanori , Lates Christian D. , Schmouder Robert 
Published: April 2018

AbstractThis open‐label, single‐sequence study in healthy subjects investigated the effects of steady‐state carbamazepine on the pharmacokinetic (PK) profile of a single 2‐mg dose of fingolimod. In period 1, a single oral dose of fingolimod 2 mg (day 1) was followed by PK and safety assessments up to 36 days. In period 2, carbamazepine was administered in flexible, up‐titrated doses (600 mg twice daily maximum) for 49 days. Fingolimod was administered on day 35, followed by a study completion evaluation (day 71). The PK analysis included 23 of 26 of the enrolled subjects (88.5%). Coadministration of fingolimod at steady‐state carbamazepine concentrations resulted in increased fingolimod CL/F by 67% through the induction of CYP3A4, a cytochrome with negligible involvement in fingolimod clearance in an uninduced state. Fingolimod Cmax was reduced by 18% and AUCinf by 40%, as was T1/2 (106 vs 163 hours). A similar trend was observed for fingolimod‐P. Models linking fingolimod‐P blood concentrations to lymphocyte count or annual relapse rate suggest that such a decrease would have a low impact on the treatment effect. However, in the absence of efficacy data of fingolimod at doses lower than the therapeutic dose, their coadministration should be used with caution.
Quantifying shorebird habitat in managed wetlands by modeling shallow water depth dynamics
Authors: Schaffer‐Smith Danica , Swenson Jennifer J. , Reiter Matthew E. , Isola Jennifer E. 
Published: April 2018

AbstractOver 50% of Western Hemisphere shorebird species are in decline due to ongoing habitat loss and degradation. In some regions of high wetland loss, shorebirds are heavily reliant on a core network of remaining human‐managed wetlands during migration journeys in the spring and fall. While most refuges have been designed and managed to match the habitat needs of waterfowl, shorebirds typically require much shallower water (<10 cm deep). Traditional static habitat modeling approaches at relatively coarse spatial and temporal resolution are insufficient to capture dynamic changes within this narrow water depth range. Our objectives were to (1) develop a method to quantify shallow water habitat distributions in inland non‐tidal wetlands, and (2) to assess how water management practices affect the amount of shorebird habitat in Sacramento National Wildlife Refuge Complex. We produced water depth distributions and modeled optimal habitat (<10 cm deep) within 23 managed wetlands using high‐resolution topography and fixed‐point water depth records. We also demonstrated that habitat availability, specifically suitable water depth ranges, can be tracked from satellite imagery and high‐resolution topography. We found that wetlands with lower topographic roughness may have a higher potential to provide shorebird habitat and that strategically reducing water levels could increase habitat extent. Over 50% of the wetlands measured provided optimal habitat across <10% of their area at the peak of migration in early April, and most provided a brief duration of shallow water habitat. Reducing water volumes could increase the proportion of optimal habitat by 1–1,678% (mean = 294%) compared to actual volumes measured at peak spring migration in 2016. For wetlands with a high habitat potential, beginning wetland drawdown earlier and extending drawdown time could dramatically improve habitat conditions at the peak of shorebird migration. Our approach can be adapted to track dynamic hydrologic changes at broader spatial scales as additional high‐resolution topographic (e.g., lidar, drone imagery photogrammetry) and optical remote sensing data (e.g., planet imagery, drone photography) become available.
Using imaging spectroscopy to detect variation in terrestrial ecosystem productivity across a water‐stressed landscape
Authors: DuBois Sean , Desai Ankur R. , Singh Aditya , Serbin Shawn P. , Goulden Michael L. , Baldocchi Dennis D. , Ma Siyan , Oechel Walter C. , Wharton Sonia , Kruger Eric L. , Townsend Philip A. 
Published: April 2018

AbstractA central challenge to understanding how climate anomalies, such as drought and heatwaves, impact the terrestrial carbon cycle, is quantification and scaling of spatial and temporal variation in ecosystem gross primary productivity (GPP). Existing empirical and model‐based satellite broadband spectra‐based products have been shown to miss critical variation in GPP. Here, we evaluate the potential of high spectral resolution (10 nm) shortwave (400–2,500 nm) imagery to better detect spatial and temporal variations in GPP across a range of ecosystems, including forests, grassland‐savannas, wetlands, and shrublands in a water‐stressed region. Estimates of GPP from eddy covariance observations were compared against airborne hyperspectral imagery, collected across California during the 2013–2014 HyspIRI airborne preparatory campaign. Observations from 19 flux towers across 23 flight campaigns (102 total image‐flux tower pairs) showed GPP to be strongly correlated to a suite of spectral wavelengths and band ratios associated with foliar physiology and chemistry. A partial least squares regression (PLSR) modeling approach was then used to predict GPP with higher validation accuracy (adjusted R2 = 0.71) and low bias (0.04) compared to existing broadband approaches (e.g., adjusted R2 = 0.68 and bias = −5.71 with the Sims et al. model). Significant wavelengths contributing to the PLSR include those previously shown to coincide with Rubisco (wavelengths 1,680, 1,740, and 2,290 nm) and Vcmax (wavelengths 1,680, 1,722, 1,732, 1,760, and 2,300 nm). These results provide strong evidence that advances in satellite spectral resolution offer significant promise for improved satellite‐based monitoring of GPP variability across a diverse range of terrestrial ecosystems.
The impact of environmental factors in birdsong acquisition using automated recorders
Authors: Priyadarshani Nirosha , Castro Isabel , Marsland Stephen 
Published: April 2018

AbstractThe use of automatic acoustic recorders is becoming a principal method to survey birds in their natural habitats, as it is relatively noninvasive while still being informative. As with any other sound, birdsong degrades in amplitude, frequency, and temporal structure as it propagates to the recorder through the environment. Knowing how different birdsongs attenuate under different conditions is useful to, for example, develop protocols for deploying acoustic recorders and improve automated detection methods, an essential part of the research field that is becoming known as ecoacoustics. This article presents playback and recapture (record) experiments carried out under different environmental conditions using twenty bird calls from eleven New Zealand bird species in a native forest and an open area, answering five research questions: (1) How does birdsong attenuation differ between forest and open space? (2) What is the relationship between transmission height and birdsong attenuation? (3) How does frequency of birdsong impact the degradation of sound with distance? (4) Is birdsong attenuation different during the night compared to the day? and (5) what is the impact of wind on attenuation? Bird calls are complex sounds; therefore, we have chosen to use them rather than simple tones to ensure that this complexity is not missed in the analysis. The results demonstrate that birdsong transmission was significantly better in the forest than in the open site. During the night, the attenuation was at a minimum in both experimental sites. Transmission height affected the propagation of the songs of many species, particularly the flightless ones. The effect of wind was severe in the open site and attenuated lower frequencies. The reverberations due to reflective surfaces masked higher frequencies (8 kHz) in the forest even at moderate distances. The findings presented here can be applied to develop protocols for passive acoustic monitoring. Even though the attenuation can be generalized to frequency bands, the structure of the birdsong is also important. Selecting a reasonable sampling frequency avoids unnecessary data accumulation because higher frequencies attenuate more in the forest. Even at moderate distances, recorders capture significantly attenuated birdsong, and hence, automated analysis methods for field recordings need to be able to detect and recognize faint birdsong.
Selective Determination of Verapamil in Pharmaceutics and Urine Using a Boron‐doped Diamond Electrode Coupled to Flow Injection Analysis with Multiple‐pulse Amperometric Detection
Authors: Barbosa Lima Amanda , Ferreira Lucas Franco , Barbosa Sandro Luiz , de Souza Gil Eric , Amorim Bezerra da Silva Rodrigo , Pio dos Santos Wallans Torres 
Published: April 2018

AbstractThis work presents a simple and low‐cost method for fast and selective determination of Verapamil (VP) in tablets and human urine samples using a boron‐doped diamond working electrode (BDD) coupled to a flow injection analysis system with multiple pulse amperometric detection (FIA‐MPA). The electrochemical behaviour of VP in 0.1 mol L−1 sulfuric acid showed three merged oxidation peaks at around +1.4 V and upon reverse scan, one reduction peak at 0.0 V (vs. Ag/AgCl). The MPA detection was performed applying a sequence of three potential pulses on BDD electrode: (1) at +1.6 V for VP oxidation, (2) at +0.2 V for reduction of the oxidized product and (3) at +0.1 V for cleaning of the working electrode surface. The FIA system was optimized with injection volume of 150 μL and flow rate of 3.5 mL min−1. The method showed a linear range from 0.8 to 40.0 μmol L−1 (R>0.99) with a low limit of detection of 0.16 μmol L−1, good repeatability (RSD<2.2 %; n=10) and sample throughput (45 h−1). Selective determination of VP in urine was performed at+0.2 V due to absence of interference from ascorbic and uric acids in this potential. The addition‐recovery tests in both samples were close to 100 % and the results were similar to an official method.
Electrocatalytic Activity of Nanohybrids Based on Carbon Nanomaterials and MFe2O4 (M=Co, Mn) towards the Reduction of Hydrogen Peroxide
Authors: Gutierrez Fabiana A. , Mazario Eva , Menéndez Nieves , Herrasti Pilar , Rubianes María D. , Zagal José H. , Yañez C. , Rivas Gustavo A. , Bollo Soledad , Recio F. Javier 
Published: April 2018

AbstractWe report the advantages of hybrid nanomaterials prepared with electrogenerated ferrites (MFe2O4; M: Co, Mn) and multi‐walled carbon nanotubes (MWCNTs) or thermally reduced graphene oxide (TRGO) on the electro‐reduction of hydrogen peroxide. Glassy carbon electrodes (GCE) modified with these hybrid nanomaterials dispersed in Nafion/isopropanol demonstrated a clear synergism on the catalytic reduction of reduction of hydrogen peroxide at pH 13.00. The intimate interaction between MFe2O4 and carbon nanomaterials allowed a better electronic transfer and a facilitated regeneration of M2+ at the carbon nanomaterials, reducing the charge transfer resistances for hydrogen peroxide reduction and increasing the sensitivities of the amperometric response.
Recombinant interleukin‐4 alleviates mechanical allodynia via injury‐induced interleukin‐4 receptor alpha in spinal microglia in a rat model of neuropathic pain
Authors: Okutani Hiroai , Yamanaka Hiroki , Kobayashi Kimiko , Okubo Masamichi , Noguchi Koichi 
Published: April 2018

AbstractGlial cells play important roles in the development and maintenance of neuropathic pain. In particular, activated microglia in the spinal cord facilitate the hyper‐excitability of dorsal horn neurons after peripheral nerve injury via pro‐inflammatory molecules. In this study, we investigated the possible involvement of the anti‐inflammatory cytokine, interleukin‐4 (IL‐4), in neuropathic pain. We did not detect the expression of IL‐4 mRNA in the rat dorsal root ganglion or spinal cord; however, peripheral nerve injury induced the expression of IL‐4 receptor (IL‐4R) alpha mRNA in the spinal cord. A histological analysis revealed that nerve injury induced IL‐4R alpha mRNA in activated spinal microglia ipsilateral to the injury site. Additionally, the increases in IL‐4R alpha were coincident with the increased expression of phosphorylated signal transducer and activator of transcription 6 (pSTAT6) in spinal microglia. Intrathecal administration of recombinant IL‐4 suppressed mechanical hypersensitivity in neuropathic rats, and the analgesic effect of IL‐4 was accompanied by further enhancement of pSTAT6 expression in spinal microglia. Taken together, these results suggest that the adaptive responses of microglia to nerve injury involve both inflammatory and anti‐inflammatory signaling, including IL‐4R alpha and pSTAT6. These findings support that utilizing the endogenous anti‐nociceptive activity of IL‐4R alpha may modify the cell lineage of pro‐nociceptive microglia, thus providing a novel therapeutic strategy for neuropathic pain.
Genetic deletion of xCT attenuates peripheral and central inflammation and mitigates LPS‐induced sickness and depressive‐like behavior in mice
Authors: Albertini Giulia , Deneyer Lauren , Ottestad‐Hansen Sigrid , Zhou Yun , Ates Gamze , Walrave Laura , Demuyser Thomas , Bentea Eduard , Sato Hideyo , De Bundel Dimitri , Danbolt Niels C. , Massie Ann , Smolders Ilse 
Published: April 2018

AbstractThe communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive‐like symptoms. In vitro, the response to LPS treatment has been shown to involve enhanced expression of system
. This cystine‐glutamate antiporter, with xCT as specific subunit, represents the main glial provider of extracellular glutamate in mouse hippocampus. Here we injected male xCT knockout and wildtype mice with a single intraperitoneal dose of 5 mg/kg LPS. LPS‐injection increased hippocampal xCT expression but did not alter the mainly astroglial localization of the xCT protein. Peripheral and central inflammation (as defined by cytokine levels and morphological activation of microglia) as well as LPS‐induced sickness and depressive‐like behavior were significantly attenuated in xCT‐deficient mice compared with wildtype mice. Our study is the first to demonstrate the involvement of system
in peripheral and central inflammation in vivo and the potential therapeutic relevance of its inhibition in brain disorders characterized by peripheral and central inflammation, such as depression.
Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia
Authors: Liu Zhaowen , Zhang Jie , Zhang Kai , Zhang Junying , Li Xiaojing , Cheng Wei , Li Mingli , Zhao Liansheng , Deng Wei , Guo Wanjun , Ma Xiaohong , Wang Qiang , Matthews Paul M. , Feng Jianfeng , Li Tao 
Published: April 2018

AbstractDisease association studies have characterized altered resting‐state functional connectivities describing schizophrenia, but failed to model symptom expression well. We developed a model that could account for symptom severity and meanwhile relate this to disease‐related functional pathology. We correlated BOLD signal across brain regions and tested separately for associations with disease (disease edges) and with symptom severity (symptom edges) in a prediction‐based scheme. We then integrated them in an “edge bi‐color” graph, and adopted mediation analysis to test for causality between the disease and symptom networks and symptom scores. For first‐episode schizophrenics (FES, 161 drug‐naïve patients and 150 controls), the disease network (with inferior frontal gyrus being the hub) and the symptom‐network (posterior occipital‐parietal cortex being the hub) were found to overlap in the temporal lobe. For chronic schizophrenis (CS, 69 medicated patients and 62 controls), disease network was dominated by thalamocortical connectivities, and overlapped with symptom network in the middle frontal gyrus. We found that symptom network mediates the relationship between disease network and symptom scores in FEP, but was unable to define a relationship between them for the smaller CS population. Our results suggest that the disease network distinguishing core functional pathology in resting‐state brain may be responsible for symptom expression in FES through a wider brain network associated with core symptoms. We hypothesize that top–down control from heteromodal prefrontal cortex to posterior transmodal cortex contributes to positive symptoms of schizophrenia. Our work also suggests differences in mechanisms of symptom expression between FES and CS, highlighting a need to distinguish between these groups.
Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition
Authors: Di Plinio Simone , Ferri Francesca , Marzetti Laura , Romani Gian Luca , Northoff Georg , Pizzella Vittorio 
Published: April 2018

AbstractRecent evidence shows that task‐deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task‐deactivated brain regions ‐ usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task‐activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally‐directed and internally‐focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.
Comparative proteomic analyses of human adipose extracellular matrices decellularized using alternative procedures
Authors: Thomas‐Porch Caasy , Li Jie , Zanata Fabiana , Martin Elizabeth C. , Pashos Nicholas , Genemaras Kaylynn , Poche J. Nicholas , Totaro Nicholas P. , Bratton Melyssa R. , Gaupp Dina , Frazier Trivia , Wu Xiying , Ferreira Lydia Masako , Tian Weidong , Wang Guangdi , Bunnell Bruce A. , Flynn Lauren , Hayes Daniel , Gimble Jeffrey M. 
Published: April 2018

AbstractDecellularized human adipose tissue has potential clinical utility as a processed biological scaffold for soft tissue cosmesis, grafting, and reconstruction. Adipose tissue decellularization has been accomplished using enzymatic‐, detergent‐, and/or solvent‐based methods. To examine the hypothesis that distinct decellularization processes may yield scaffolds with differing compositions, the current study employed mass spectrometry to compare the proteomes of human adipose‐derived matrices generated through three independent methods combining enzymatic‐, detergent‐, and/or solvent‐based steps. In addition to protein content, bioscaffolds were evaluated for deoxyribose nucleic acid depletion, extracellular matrix composition, and physical structure using optical density, histochemical staining, and scanning electron microscopy. Mass spectrometry based proteomic analyses identified 25 proteins (having at least two peptide sequences detected) in the scaffolds generated with an enzymatic approach, 143 with the detergent approach, and 102 with the solvent approach, as compared to 155 detected in unprocessed native human fat. Immunohistochemical detection confirmed the presence of the structural proteins actin, collagen type VI, fibrillin, laminin, and vimentin. Subsequent in vivo analysis of the predominantly enzymatic‐ and detergent‐based decellularized scaffolds following subcutaneous implantation in GFP+ transgenic mice demonstrated that the matrices generated with both approaches supported the ingrowth of host‐derived adipocyte progenitors and vasculature in a time dependent manner. Together, these results determine that decellularization methods influence the protein composition of adipose tissue‐derived bioscaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2481–2493, 2018.