bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentially sensitive neuronal subpopulations in the central nervous system and the formation of hindbrain heterotopias in ethanol‐exposed zebrafish
Authors: Buckley Desire M. , Sidik Alfire , Kar Ranjeet D. , Eberhart Johann K. 
Published: February 2019

BackgroundA cardinal feature of prenatal ethanol exposure is CNS damage, resulting in a continuum of neurological and behavioral impairments that are described by the term fetal alcohol spectrum disorders (FASD). FASDs are variable and depend on several factors, including the amount, timing, and duration of prenatal ethanol exposure. To enhance interventions for CNS dysfunction, it is necessary to identify ethanol‐sensitive neuronal populations and expand the understanding of factors that modify ethanol teratogenesis.MethodsTo investigate the susceptibility of different neuronal subtypes, we exposed transgenic zebrafish (Danio rerio) to several ethanol concentrations (0.25, 0.5, 1.0, 1.5, or 2.0%), at different hours post fertilization (hpf; 0, 6, or 24 hpf), for various durations (0–24, 0–48, 4–24, 6–24, 6–48,or 24–48 hpf). Following exposure, embryo survival rates were determined, and CNS neurogenesis, differentiation, and patterning were assessed.ResultsEmbryo survival rates decrease as ethanol concentrations increase and drastically decline when exposed from 0–24 hpf compared to 4–24 hpf. Abnormal tangential migration of facial motor neurons is observed in isl1:gfp embryos exposed to ethanol concentrations as low as 0.25%, and the formation of IVth ventricle heterotopias are revealed by embryos exposed to ≥1.0% ethanol. Whereas, expression of olig2:dsred and ptf1a:gfp in the cerebellum and spinal cord are largely unaffected. While levels of etv4 mRNA are overtly resistant to ethanol, we observe significant reductions in ptch2 mRNA levels.ConclusionsThese data show differentially sensitive CNS neuron subpopulations with susceptibility to low levels of ethanol. In addition, these data reveal the formation of ethanol‐induced hindbrain heterotopias.
Stable isotope dilution assay for the accurate determination of tricaine in fish samples by HPLC–MS–MS
Authors: Xie Chaonan , Li Qin , Han Gang , Liu Huan , Yang Jien , Li Jincheng 
Published: February 2019

AbstractTricaine methanesulfonate is one of most commonly used anesthetics in fish during blood sampling, artificial propagation and long‐distance transportation. In this study, an accurate method for the quantitative determination of tricaine in fish samples by a stable isotope dilution assay coupled with high‐performance liquid chromatography–triple quadrupole mass spectrometry was developed. Tricaine‐D5 was synthesized and used as an isotopically labeled internal standard for the determination of tricaine. The analytical performance of the method was validated for tricaine determination in marine fish and freshwater fish. The determination of tricaine was linear in the range of 2.0–200.0 μg L−1. The limit of detection and limit of quantitation for fish muscle tissues were 1.0 and 4.0 μg kg−1, respectively. Good recoveries were obtained in the range of 92.08–97.50%. The inter‐ and intra‐assay relative standard deviations (RSD values) were investigated, and the values were 0.39–3.01 and 0.85–2.77%, respectively. The values of CCα and CCβ were 10.21–10.43 and 10.42–10.87 μg kg−1, respectively. The clearance of MS‐222 from grass carp was further studied using our method. The results demonstrate that MS‐222 could be well absorbed and rapidly eliminated after bath administration.
Cumulative evidence for association between genetic polymorphisms and esophageal cancer susceptibility: A review with evidence from meta‐analysis and genome‐wide association studies
Authors: Tian Jie , Liu Caiyang , Liu Guanchu , Zuo Chunjian , Chen Huanwen 
Published: February 2019

AbstractAn increasing number of publications had reported the association between single‐nucleotide polymorphisms (SNPs) and esophageal cancer (EC) risk in the past decades. Results from these publications were controversial. We used PubMed, Medline, and Web of Science to identify meta‐analysis articles published before 30 July 2018, that summarize a comprehensive investigation for cumulative evidence of genetic polymorphisms of EC and its subtype risk. Two methods, Venice criteria and false‐positive report probability (FPRP) tests, were used to assess cumulative evidence of significant associations. At last, 107 meta‐analyses were considered to be in conformity with the inclusion criteria, yielding 51 variants associated with EC or esophageal squamous cell carcinoma (ESCC). Thirty‐eight variants were considered to be nominally significant associated with risk of EC or ESCC, whereas the rest showed non‐association. In additional, five variants on five genes were rated as strong cumulative epidemiological evidence for a nominally significant association with EC and ESCC risk, including CYP1A1 rs1048943, EGF rs444903, HOTAIR rs920778, MMP2 rs243865, and PLCE1 rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak. Additionally, 17 SNPs were verified noteworthy in six genomewide association studies (GWAS) using FPRP methods. Collectively, this review offered a comprehensively referenced information with cumulative evidence of associations between genetic polymorphisms and EC and ESCC risk.
Magnolol induces cell death through PI3K/Akt‐mediated epigenetic modifications boosting treatment of BRAF‐ and NRAS‐mutant melanoma
Authors: Emran Abdullah Al , Chinna Chowdary Brinda Reddy , Ahmed Farzana , Hammerlindl Heinz , Huefner Antje , Haass Nikolas K. , Schuehly Wolfgang , Schaider Helmut 
Published: February 2019

AbstractMost BRAF‐mutant melanoma patients experience a fulminate relapse after several months of treatment with BRAF/MEK inhibitors. To improve therapeutic efficacy, natural plant‐derived compounds might be considered as potent additives. Here, we show that magnolol, a constituent of Magnolia officinalis, induced G1 arrest, apoptosis and cell death in BRAF‐ and NRAS‐mutant melanoma cells at low concentration, with no effect in BRAF‐ and NRAS wild‐type melanoma cells and human keratinocytes. This was confirmed in a 3D spheroid model. The apoptosis‐inducing effect of magnolol was completely rescued by activating Akt suggesting a mechanism relying primarily on Akt signaling. Magnolol significantly downregulated the PI3K/Akt pathway which led to a global decrease of the active histone mark H3K4me3. Alongside, the repressive histone mark H3K9me3 was increased as a response to DNA damage. Magnolol‐induced alterations of histone modifications are reversible upon activation of the Akt pathway. Magnolol‐induced a synergistic effect in combination with either BRAF/MEK inhibitors dabrafenib/trametinib or docetaxel at a lower concentration than usually applied in melanoma patients. Combination of magnolol with targeted therapy or chemotherapy also led to analogous effects on histone marks, which was rescued by Akt pathway activation. Our study revealed a novel epigenetic mechanism of magnolol‐induced cell death in melanoma. Magnolol might therefore be a clinically useful addition to BRAF/MEK inhibitors with enhanced efficacy delaying or preventing disease recurrence.
Volatile Chemical Composition, Antibacterial and Antifungal Activities of Extracts from Different Parts of Globba schomburgkii Hook.f.
Authors: Doungchawee Jeerapat , Kulsing Chadin , Suekaew Naruemon , Na Pombejra Sarisa , Chavasiri Warinthorn , Plabutong Napasawan , Thammahong Arsa , Khotavivattana Tanatorn 
Published: February 2019

AbstractGlobba schomburgkii Hook.f. is an ornamental plant that has recently found increasing demand as cut flowers, hence generating a significant number of by‐products from different parts of the plant. To investigate the further applications of these by‐products, twelve crude extracts from rhizomes, stalks, leaves, and flowers were prepared by serial exhaustive extraction. The volatile composition of these extracts was analyzed by GC/MS; a total of 89 compounds were identified, most of which were sesquiterpenes as well as some labdane‐type diterpenes. The antimicrobial activities of these extracts were evaluated, revealing a correlation between the terpenoid content and antibacterial activities. Notably, the dichloromethane extracts of rhizomes and flowers, which contained the highest amount of terpenoids (e. g., α‐gurjunene, guaia‐9,11‐diene, γ‐bicyclohomofarnesal, β‐caryophyllene, and caryophyllene oxide), displayed the most prominent antibacterial activities. This work demonstrates the potential use of the crude extracts from G. schomburgkii as natural antibacterial ingredients for pharmaceutical and other applications.
Tailored Hollow Core/Mesoporous Shell Carbon Nanofibers as Highly Efficient and Durable Cathode Catalyst Supports for Polymer Electrolyte Fuel Cells
Authors: Karuppanan Karthikeyan K. , Raghu Appu V. , Panthalingal Manoj Kumar , Pullithadathil Biji 
Published: February 2019

AbstractAn electrocatalyst support material based on hierarchical mesoporous hollow carbon nanofibers (mPHCNFs) has been developed by co‐axial electrospinning and has been deployed for the fabrication of polymer electrolyte membrane fuel cells (PEMFCs). The synergistic effect of a high specific surface area (780 m2/g), homogeneous formation of mesopores (20–50 nm), and hollow nanochannels in the carbon nanofiber matrix lead to the uniform distribution of Pt electrocatalysts. XPS analysis revealed that the presence of nitrogen species in the mesoporous hollow carbon nanofibers in the form of pyridinic, pyrrolic, and quaternary nitrogen atoms played a crucial role in the augmentation of triple‐phase boundaries. Pt/mPHCNFs exhibited superior electrocatalytic activity towards the oxygen reduction reaction with a positively shifted onset potential (62 mV) and half‐wave potential (86 mV) as well as a high limiting current density (4.76 mA/cm2) compared to commercial electrocatalysts. The Pt/mPHCNFs catalyst exhibited excellent stability in acidic medium and showed only 23 mV loss in the half‐wave potential; whereas, Pt/CNFs (35 mV) and Pt/C (77 mV) exhibited a much higher shift in half‐wave potential. The PEMFC testing of the membrane electrode assembly based on Pt/mPHCNFs (411 mW/cm2) revealed a superior performance compared to Pt/CNFs (297.4 mW/cm2) and Pt/C (212.8 mW/cm2). This method can offer an effective strategy for the development of durable, low‐cost, and high‐performance PEMFCs.
Uncatalyzed Oxidative C−H Amination of 9,10‐Dihydro‐9‐Heteroanthracenes: A Mechanistic Study
Authors: van Leest Nicolaas P. , Grooten Lars , van der Vlugt Jarl Ivar , de Bruin Bas 
Published: February 2019

AbstractA new method for the one‐step C−H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone was employed as a hydride (or two‐electron and one‐proton) acceptor. Moreover, a previously unknown and uncatalyzed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10‐dihydro‐9‐heteroanthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed through hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal‐catalyzed C−H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C−H bond, xanthene is an often‐employed substrate in mechanistic studies of C−H amination reactions, which are generally proposed to proceed via metal‐catalyzed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e., less strongly oxidizing). However, these substrates clearly undergo non‐catalyzed (proton‐coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal‐catalyzed pathways.
Polyhydroxyalkanoate‐Modified Bacterium Regulates Biomass Structure and Promotes Synthesis of Carbon Materials for High‐Performance Supercapacitors
Authors: Zhang Kejing , Liu Mingren , Si Mengying , Wang Zhongren , Zhuo Shengnan , Chai Liyuan , Shi Yan 
Published: February 2019

AbstractBiomass‐derived carbons have been extensively explored as electrode materials in supercapacitors. However, the type of biomass selected and its specific structure affects the synthesis of the advanced biomass‐derived carbon materials. A green and facile method for the synthesis of carbon material with nanoscale and microscale porous structures for supercapacitors has been developed, based on regulating the original cell structure of the bacterial strain. The cell structure is modified in situ by regulating the accumulation of polyhydroxyalkanoate under controlled cultivation conditions. The novel bacterial in situ modification and nitrogen doping endow this hierarchically derived carbon material with improved performance. This material exhibits an extremely high specific capacitance (420 F g−1 at 1 A g−1) and long cycling stability (97 % capacitance retention after 10 000 cycles at 5 A g−1) in aqueous electrolytes. More importantly, the symmetric supercapacitor delivers a superior energy density of 60.76 Wh kg−1 at 625 W kg−1 in an ionic liquid electrolyte system. Moreover, all components in the synthesis are low in cost, environmentally friendly, and biocompatible. With these unique features, the bacterial self‐modification mode opens new avenues into the design and production of a wide range of hierarchical structures.
Correlation of cytopathology with flow cytometry and histopathology for the diagnosis of hematologic malignancies in young adults presenting with cervical lymphadenopathy
Authors: Choy Bonnie , Venkataraman Girish , Biernacka Anna , Lastra Ricardo R. , Mueller Jeffery , Setia Namrata , Reeves Ward , Antic Tatjana 
Published: February 2019

BackgroundFine‐needle aspiration (FNA) is frequently utilized in the diagnostic workup of lymphadenopathy. We evaluated the correlation of cytopathology with flow cytometry and tissue biopsy results and assessed the prevalence of specific malignancies in young adults presenting with cervical lymphadenopathy.MethodsDatabase was searched for cervical lymph node FNA performed by a cytopathologist in patients aged 18‐30 years from 2005 to 2017.ResultsCervical lymph node FNA was performed on 48 patients without prior history of malignancy. Nineteen patients had cytology results only, of which all were interpreted as benign reactive lymph node. None developed subsequent malignancies. The remaining 29 patients had cytology with flow cytometry and/or tissue biopsy results. A benign reactive cytology diagnosis was rendered in 18 (62%) cases, of which 11 had concordant diagnosis on flow cytometry, 2 had tissue biopsy, and 3 had both. Eleven (38%) patients had cytology results concerning for a hematologic malignancy, of which 7 were confirmed by flow cytometry and 3 by both flow cytometry and tissue biopsy. Cervical lymph node FNA has 94.1% sensitivity, 83.3% specificity, 88.9% positive predictive value, and 90.9% negative predictive value. The most common hematologic malignancy in our young adult population presenting with cervical lymphadenopathy was Hodgkin lymphoma.ConclusionFNA is a useful first‐line diagnostic procedure for assessing cervical lymphadenopathy in young adults to allow for better triage of specimens for flow cytometry and/or tissue biopsy concerning for a hematologic malignancy and potentially avoid invasive excisional biopsy in a proportion of cases.
Transcriptome analysis predicts mode of action of benzimidazole molecules against Staphylococcus aureus UAMS‐1
Authors: Chauhan Deepika , Hati Santanu , Priyadarshini Richa , Sen Subhabrata 
Published: February 2019

AbstractAntimicrobial drug resistance is one of the most critical problems that plagued the human race in modern times. Discovery of novel antibiotics is important to counter this threat. Accordingly, herein we have reported the discovery of substituted benzimidazole class of molecules with antimicrobial property (specifically against Staphylococcus aureus). They were initially identified through a random screening and a novel catalytic synthetic strategy was utilized to access them. in vitro screening and phenotypic profiling revealed the antimicrobial nature. De novo transcriptome and gene analyses predicted the putative targets. This work provides a solid foundation for developing the benzimidazoles as a target specific antimicrobial preclinical candidate.
A comparison of techniques for classifying behavior from accelerometers for two species of seabird
Authors: Patterson Allison , Gilchrist Hugh Grant , Chivers Lorraine , Hatch Scott , Elliott Kyle 
Published: February 2019

AbstractThe behavior of many wild animals remains a mystery, as it is difficult to quantify behavior of species that cannot be easily followed throughout their daily or seasonal movements. Accelerometers can solve some of these mysteries, as they collect activity data at a high temporal resolution (<1 s), can be relatively small (<1 g) so they minimally disrupt behavior, and are increasingly capable of recording data for long periods. Nonetheless, there is a need for increased validation of methods to classify animal behavior from accelerometers to promote widespread adoption of this technology in ecology. We assessed the accuracy of six different behavioral assignment methods for two species of seabird, thick‐billed murres (Uria lomvia) and black‐legged kittiwakes (Rissa tridactyla). We identified three behaviors using tri‐axial accelerometers: standing, swimming, and flying, after classifying diving using a pressure sensor for murres. We evaluated six classification methods relative to independent classifications from concurrent GPS tracking data. We used four variables for classification: depth, wing beat frequency, pitch, and dynamic acceleration. Average accuracy for all methods was >98% for murres, and 89% and 93% for kittiwakes during incubation and chick rearing, respectively. Variable selection showed that classification accuracy did not improve with more than two (kittiwakes) or three (murres) variables. We conclude that simple methods of behavioral classification can be as accurate for classifying basic behaviors as more complex approaches, and that identifying suitable accelerometer metrics is more important than using a particular classification method when the objective is to develop a daily activity or energy budget. Highly accurate daily activity budgets can be generated from accelerometer data using multiple methods and a small number of accelerometer metrics; therefore, identifying a suitable behavioral classification method should not be a barrier to using accelerometers in studies of seabird behavior and ecology.
Geographic patterns in morphometric and genetic variation for coyote populations with emphasis on southeastern coyotes
Authors: Hinton Joseph W. , Heppenheimer Elizabeth , West Kyla M. , Caudill Danny , Karlin Melissa L. , Kilgo John C. , Mayer John Joseph , Miller Karl V. , Walch Margaret , vonHoldt Bridgett , Chamberlain Michael J. 
Published: February 2019

AbstractPrior to 1900, coyotes (Canis latrans) were restricted to the western and central regions of North America, but by the early 2000s, coyotes became ubiquitous throughout the eastern United States. Information regarding morphological and genetic structure of coyote populations in the southeastern United States is limited, and where data exist, they are rarely compared to those from other regions of North America. We assessed geographic patterns in morphology and genetics of coyotes with special consideration of coyotes in the southeastern United States. Mean body mass of coyote populations increased along a west‐to‐east gradient, with southeastern coyotes being intermediate to western and northeastern coyotes. Similarly, principal component analysis of body mass and linear body measurements suggested that southeastern coyotes were intermediate to western and northeastern coyotes in body size but exhibited shorter tails and ears from other populations. Genetic analyses indicated that southeastern coyotes represented a distinct genetic cluster that differentiated strongly from western and northeastern coyotes. We postulate that southeastern coyotes experienced lower immigration from western populations than did northeastern coyotes, and over time, genetically diverged from both western and northeastern populations. Coyotes colonizing eastern North America experienced different selective pressures than did stable populations in the core range, and we offer that the larger body size of eastern coyotes reflects an adaptation that improved dispersal capabilities of individuals in the expanding range.
Reproducibility of a battery of human evoked pain models to detect pharmacological effects of analgesic drugs
Authors: Siebenga Pieter S. , van Amerongen Guido , Okkerse Pieter , Denney William S. , Dua Pinky , Butt Richard P. , Hay Justin L. , Groeneveld Geert J. 
Published: February 2019

AbstractBackgroundAlthough reproducibility is considered essential for any method used in scientific research, it is investigated only rarely; thus, strikingly little has been published regarding the reproducibility of evoked pain models involving human subjects. Here, we studied the reproducibility of a battery of evoked pain models for demonstrating the analgesic effects of two analgesic compounds.MethodsA total of 81 healthy subjects participated in four studies involving a battery of evoked pain tests in which mechanical, thermal and electrical stimuli were used to measure pain detection and tolerance thresholds. Pharmacodynamic outcome variables were analysed using a mixed model analysis of variance, and a coefficient of variation was calculated by dividing the standard deviation by the least squares means.ResultsA total of 76 subjects completed the studies. After being administered pregabalin, the subjects’ pain tolerance thresholds in the cold pressor and pressure stimulation tests were significantly increased compared to the placebo group. Moreover, the heat pain detection threshold in UVB‐irradiated skin was significantly increased in subjects who were administered ibuprofen compared to the placebo group. Variation among all evoked pain tests ranged from 2.2% to 30.6%.ConclusionsFour studies using a similar design showed reproducibility with respect to the included evoked pain models. The relatively high consistency and reproducibility of two analgesics at doses known to be effective in treating clinically relevant pain supports the validity of using this pain test battery to investigate the analgesic activity and determine the active dosage of putative analgesic compounds in early clinical development.SignificanceThe consistency and reproducibility of measuring the profile of an analgesic at clinically relevant doses illustrates that this pain test battery is a valid tool for demonstrating the analgesic activity of a test compound and for determining the optimal active dose in early clinical drug development.