bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Artemisinin‐Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action
Authors: Fröhlich Tony , Hahn Friedrich , Belmudes Lucid , Leidenberger Maria , Friedrich Oliver , Kappes Barbara , Couté Yohann , Marschall Manfred , Tsogoeva Svetlana B.
Published: March 2018

Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin‐derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 μm) and artesunic acid (EC50 5.41 μm). In addition, artemisinin‐derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF‐Amino‐650M beads and used for mass spectrometry‐based target identification experiments using total lysates of HCMV‐infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound‐binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified.
Water Splitting on Rutile TiO2‐Based Photocatalysts
Authors: Miyoshi Akinobu , Nishioka Shunta , Maeda Kazuhiko
Published: March 2018

Water splitting using a semiconductor photocatalyst with sunlight has long been viewed as a potential means of large‐scale H2production from renewable resources. Different from anatase TiO2, rutile enables preferential water oxidation, which is useful for the construction of a Z‐scheme water‐splitting system. The combination of rutile TiO2with a suitable H2‐evolution photocatalyst such as a Pt‐loaded BaZrO3–BaTaO2N solid solution enables solar‐driven water splitting into H2and O2. While rutile TiO2is a wide‐gap semiconductor with a bandgap of 3.0 eV, co‐doping of rutile TiO2with certain metal ions and/or nitrogen produces visible‐light‐driven photocatalysts, which are also useful as a component for water oxidation in visible‐light‐driven Z‐scheme water splitting. The key to achieving highly efficient water oxidation is to maintain a charge balance of dopants in the rutile, because single doping typically produces trap states that capture photogenerated electrons and/or holes. Here we provide a concise summary of rutile TiO2‐based photocatalysts for water‐splitting systems.
Identification of clinically relevant phenotypes in patients with Ebstein anomaly
Authors: Cabrera Rodrigo , Miranda‐Fernández Marta Catalina , Huertas‐Quiñones Victor Manuel , Carreño Marisol , Pineda Ivonne , Restrepo Carlos M. , Silva Claudia Tamar , Quero Rossi , Cano Juan David , Manrique Diana Carolina , Camacho Camila , Tabares Sebastián , García Alberto , Sandoval Néstor , Moreno Medina Karen Julieth , Dennis Verano Rodolfo José
Published: March 2018

Background

Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes.

Hypothesis

Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors.

Methods

A comprehensive cross‐sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis.

Results

The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff‐Parkinson‐White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities.

Conclusions

This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting.
Cardioversion of persistent atrial fibrillation is associated with a 24‐hour relapse gap: Observations from prolonged postcardioversion rhythm monitoring
Authors: Weijs Bob , Limantoro Ione , Delhaas Tammo , de Vos Cees B. , Blaauw Yuri , Houben Richard P. M. , Verheule Sander , Pisters Ronny , Crijns Harry J. G. M.
Published: March 2018

Background

Many recurrences occur after electrical cardioversion (ECV) of atrial fibrillation (AF). Assessment of extent of remodeling and continuous prolonged rhythm monitoring might reveal actionable recurrence mechanisms.

Hypothesis

After ECV of AF specific patterns of arrhythmia recurrence can be distinguished.

Methods

All patients who underwent successful ECV due to persistent AF were included. Tissue velocity echocardiography during AF was performed before ECV to study atrial fibrillatory cycle length and fibrillatory velocity. After ECV, the heart rhythm of all patients was monitored 3 times daily during 4 weeks, and timing of recurrence was noted.

Results

In total, 50 patients (68% male) were included; mean age was 68 ± 9 years. Median duration of the current AF episode was 102 (range, 74–152) days. Twenty‐one (42%) patients showed recurrence of persistent AF. No recurrences occurred during the first 24 hours. There were no differences in clinical characteristics between patients with or without recurrence of AF. However, patients with early recurrence of AF had significantly higher precardioversion wall‐motion velocity compared with patients who remained in sinus rhythm (2.8 [1.6–3.6] vs 1.4 [0.9–3.3] cm/s; P = 0.017), whereas atrial fibrillatory cycle length did not differ.

Conclusions

In this study on 50 patients successfully cardioverted for persistent AF, there was a relapse gap of ≥24 hours. This phenomenon has not been well appreciated before and offers an AF‐free window of opportunity for electrocardiographically triggered cardiac imaging or complex electrophysiological procedures. Echocardiographic tissue velocity imaging may visualize atrial remodeling relevant to AF recurrence.
Steric Hindrance in Sulfur Vacancy of Monolayer MoS2 Boosts Electrochemical Reduction of Carbon Monoxide to Methane
Authors: Chen Zhi Wen , Gao Wang , Zheng Wei Tao , Jiang Qing
Published: March 2018

The efficient generation of methane by total electroreduction of carbon monoxide (CO) could be of benefit for a more sustainable society. However, a highly efficient and selective catalyst for this process remains to be developed. In this study, density functional theory calculations indicate that steric hindrance in monolayer molybdenum sulfide with 2 S vacancies (DV‐MoS2) can facilitate the conversion of CO into CH4 with high activity and selectivity under electrochemical reduction at a low potential of −0.53 V vs. RHE and ambient conditions. The potential is a significant improvement on the state‐of‐the‐art Cu electrode (−0.74 V vs. RHE), with less electrical energy. Moreover, the results suggest that such steric hindrance effects are important for structure‐sensitive catalytic reactions.
An investigation of the monoamine oxidase inhibition properties of pyrrolo[3,4‐f]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives
Authors: Chirkova Zhanna V. , Kabanova Mariya V. , Filimonov Sergey I. , Abramov Igor G. , Petzer Anél , Engelbrecht Idalet , Petzer Jacobus P. , Yu Suponitsky Kyrill , Veselovsky Alexander V.
Published: March 2018

Hit, Lead & Candidate Discovery

In recent studies, we have shown that pyrrolo[3,4‐f]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives act as good potency in vitro inhibitors of the monoamine oxidase (MAO) enzymes. To expand on these series and to further derive structure‐activity relationships (SARs) for MAO inhibition, in the present study we synthesized additional homologs and related analogs of these chemical classes. Analyzes of the MAO inhibition properties of the synthesized compounds show that among the pyrrolo[3,4‐f]indole‐5,7‐dione derivatives good potency MAO inhibitors exist as exemplified by 10, which possesses IC50 values for the inhibition of MAO‐A and MAO‐B of 0.023 and 0.178 µM, respectively. Among thirteen pyrrolo[3,4‐f]indole‐5,7‐diones, nine compounds exhibit IC50 values for the inhibition of an MAO isoform in the submicromolar range. It may be concluded that active MAO inhibitors, such as 10 represent suitable leads for the development of drugs for neurodegenerative and neuropsychiatric disorders such as Parkinson's disease and depression. MAO inhibitors are also of interest for the treatment of prostate cancer, certain types of cardiomyopathies and Alzheimer's disease.
Temporally restricted death and the role of p75NTR as a survival receptor in the developing sensory nervous system
Authors: Cheng Irene , Jin Lucy , Rose Lucy C. , Deppmann Christopher D.
Published: March 2018

The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target‐derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), nonpeptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+). A direct comparison of early developmental timing between these subsets has not been performed. Here we characterized the accumulation and death of TrkA, B, C, and Ret+ neurons in the DRG as a function of developmental time. We find that TrkB, TrkC, and Ret‐expressing neurons in the DRG complete developmental cell death prior to TrkA‐expressing neurons. Given the broadly defined roles of the neurotrophin receptor p75NTR in augmenting neurotrophic signaling in sensory neurons, we investigated its role in supporting the survival of these distinct subpopulations. We find that TrkA+, TrkB+, and TrkC+ sensory neuron subpopulations require p75NTR for survival, but proliferating progenitors do not. These data demonstrate how diverging sensory neurons undergo successive waves of cell death and how p75NTR represses the magnitude, but not developmental window of this culling. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 701–717, 2018
Investigation of phenylbutazone and its metabolite oxyphenbutazone in horse meat products during years 2013–2017
Authors: Annunziata Loredana , Visciano Pierina , Stramenga Arianna , Colagrande Maria Novella , Campana Guido , Scortichini Giampiero , Migliorati Giacomo , Compagnone Dario
Published: March 2018

This study showed the results of a monitoring program aimed at detecting the fraudulent use of horse meat in samples collected in the framework of official controls during the years 2013–2017 after the so‐called horse meat scandal that caused a decreasing consumer confidence in the food industry, particularly in meat products. A total of 125 samples diversely distributed in the 5 years of monitoring were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method was validated according to Commission Decision 657/2002/EC with regard to the following parameters: linearity, specificity, decision limit (CCα), detection capability (CCβ), recovery, and precision (repeatability and within‐laboratory reproducibility). Even if the results of this study revealed no positive sample, the need for constant assurance of food safety and consumers' health protection requires the implementation of preventive as well as corrective actions in the management of risks linked to the food chain in a more global context.
A novel podoplanin‐GFPCre mouse strain for gene deletion in lymphatic endothelial cells
Authors: Gil Hyea Jin , Ma Wanshu , Oliver Guillermo
Published: March 2018

The lymphatic vascular system is a one‐direction network of thin‐walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice. Unfortunately, only few mouse Cre strains relatively specific for lymphatic endothelial cells (LECs) are currently available. In this article, we report the generation of a novel Podoplanin (Pdpn) GFPCre transgenic mouse strain using its 5’ regulatory region. Pdpn encodes a transmembrane mucin‐type O‐glycoprotein that is expressed on the surface of embryonic and postnatal LECs, in addition to few other cell types. Our detailed characterization of this novel strain indicates that it will be a valuable additional genetic tool for the analysis of gene function in LECs.
Reforming of Coal Gasification Gas by a Packed‐bed Dielectric Barrier Discharge
Authors: HOSOI SHOGO , TAKAHASHI KAZUHIRO , SATOH KOHKI , ITAKURA KEN‐ICHI
Published: March 2018

An artificial underground coal gasification (UCG) gas is generated by heating crushed coal, the artificial UCG gas is reformed by a packed‐bed dielectric barrier discharge (PB‐DBD), and then the reforming characteristics of the UCG gas are investigated. H2S, H2, CH4, CO, CO2, N2, and O2, which have been known as typical UCG gas components, are found to be contained in the gas, and alkanes (CnH2n+2), alkenes (CnH2n), and so on are also detected. When the UCG gas containing H2S of 400 ppm is reformed at an input power of 40W and a flow rate of 0.1 L/min, it is found that the decomposition rate and the decomposition efficiency of H2S are approximately 80% and 1.94 mmol/kWh, respectively, and that the production amount of H2 increases by approximately 14−40% and the production efficiency of H2 is 81.4 mmol/kWh. It is also found that the concentration of alkenes decreases obviously, while the concentration of alkanes is not affected significantly by discharge plasma reforming. This indicates that H2 may be produced from alkenes contained in the UCG gas by discharge plasma reforming. This leads that desulfurization and H2 production can be done simultaneously in a single reactor.
Ecological data for western Indian Ocean tuna
Authors: Bodin Nathalie , Chassot Emmanuel , Sardenne Fany , Zudaire Iker , Grande Maitane , Dhurmeea Zahirah , Murua Hilario , Barde Julien
Published: March 2018

Tuna are marine apex predators that inhabit the tropical and sub‐tropical waters of the Indian Ocean where they support socially and economically important fisheries. Key component of pelagic communities, tuna are bioindicator species of anthropogenic and climate‐induced changes through modifications of the structure and related energy‐flow of food webs and ecosystems. The IndianEcoTuna dataset provides a panel of ecological tracers measured in four soft tissues (white muscle, red muscle, liver, gonads) from 1,364 individuals of four species, i.e., the albacore (ALB, Thunnus alalunga), the bigeye (BET, T.‐obesus), the skipjack (SKJ, Katsuwomus pelamis), and the yellowfin (YFT, T.‐albacares), collected throughout the western Indian Ocean from 2009 to 2015. Sampling was carried out during routine monitoring programs, at sea by observers onboard professional vessels or at landing. For each record, the type of fishing gear, the conservation mode, as well as the fishing date and catch location are provided. Individuals were sampled to span a wide range of body sizes: 565 ALB with fork length from 58 to 118‐cm, 155 BET from 29.5 to 173‐cm, 304 SKJ from 30 to 74‐cm, and 340 YFT from 29 to 171.5‐cm. The IndianEcoTuna dataset combines: (1) 9,512 records of carbon and nitrogen stable isotopes (percent element weights, ‐13C and ‐15N values) in 1,185 fish, (2) 887 concentrations of total proteins in 242 fish, (3) 8,356 concentrations of total lipids and three lipid classes (triacylglycerols TAG; phospholipids PL; sterols ST) in 695 fish, and (4) 1,150 and 1,033 profiles of neutral and polar fatty acids in 397 and 342 fish, respectively. Information on sex and weights of the whole fish, gonads, liver and stomach is provided. Because of the essential trophic role and wide‐ranging of tuna in marine systems, and the large panel of tropho‐energetic tracers and derived‐key quantitative parameters provided (e.g., niche width, trophic position, condition indices), the IndianEcoTuna dataset should be of high interest for global and regional research on marine trophic ecology and food web analysis, as well as on the impacts of anthropogenic changes on Indian Ocean marine ecosystems. There are no copyright restrictions for research and/or teaching purposes. Usage of the dataset must include citation of this Data Paper.
Predicting ecosystem vulnerability to biodiversity loss from community composition
Authors: Heilpern Sebastian A. , Weeks Brian C. , Naeem Shahid
Published: March 2018

Ecosystems vary widely in their responses to biodiversity change, with some losing function dramatically while others are highly resilient. However, generalizations about how species‐ and community‐level properties determine these divergent ecosystem responses have been elusive because potential sources of variation (e.g., trophic structure, compensation, functional trait diversity) are rarely evaluated in conjunction. Ecosystem vulnerability, or the likely change in ecosystem function following biodiversity change, is influenced by two types of species traits: response traits that determine species’ individual sensitivities to environmental change, and effect traits that determine a species’ contribution to ecosystem function. Here we extend the response‐effect trait framework to quantify ecosystem vulnerability and show how trophic structure, within‐trait variance, and among‐trait covariance affect ecosystem vulnerability by linking extinction order and functional compensation. Using in silico trait‐based simulations we found that ecosystem vulnerability increased when response and effect traits positively covaried, but this increase was attenuated by decreasing trait variance. Contrary to expectations, in these communities, both functional diversity and trophic structure increased ecosystem vulnerability. In contrast, ecosystem functions were resilient when response and effect traits covaried negatively, and variance had a positive effect on resiliency. Our results suggest that although biodiversity loss is often associated with decreases in ecosystem functions, such effects are conditional on trophic structure, and the variation within and covariation among response and effect traits. Taken together, these three factors can predict when ecosystems are poised to lose or gain function with ongoing biodiversity change.
Contrasting drivers and trends of coniferous and deciduous tree growth in interior Alaska
Authors: Cahoon Sean M. P. , Sullivan Patrick F. , Brownlee Annalis H. , Pattison Robert R. , Andersen Hans‐Erik , Legner Kate , Hollingsworth Teresa N.
Published: March 2018

The boreal biome represents approximately one third of the world's forested area and plays an important role in global biogeochemical and energy cycles. Numerous studies in boreal Alaska have concluded that growth of black and white spruce is declining as a result of temperature‐induced drought stress. The combined evidence of declining spruce growth and changes in the fire regime that favor establishment of deciduous tree species has led some investigators to suggest the region may be transitioning from dominance by spruce to dominance by deciduous forests and/or grasslands. Although spruce growth trends have been extensively investigated, few studies have evaluated long‐term radial growth trends of the dominant deciduous species (Alaska paper birch and trembling aspen) and their sensitivity to moisture availability. We used a large and spatially extensive sample of tree cores from interior Alaska to compare long‐term growth trends among contrasting tree species (white and black spruce vs. birch and aspen). All species showed a growth peak in the mid‐1940s, although growth following the peak varied strongly across species. Following an initial decline from the peak, growth of white spruce showed little evidence of a trend, while black spruce and birch growth showed slight growth declines from ~1970 to present. Aspen growth was much more variable than the other species and showed a steep decline from ~1970 to present. Growth of birch, black and white spruce was sensitive to moisture availability throughout most of the tree‐ring chronologies, as evidenced by negative correlations with air temperature and positive correlations with precipitation. However, a positive correlation between previous July precipitation and aspen growth disappeared in recent decades, corresponding with a rise in the population of the aspen leaf miner (Phyllocnistis populiella), an herbivorous moth, which may have driven growth to a level not seen since the early 20th century. Our results provide important historical context for recent growth and raise questions regarding competitive interactions among the dominant tree species and exchanges of carbon and energy in the warming climate of interior Alaska.
Transition‐Metal‐Free Radical Hydrotrifluoromethylation of Alkynes
Authors: Matcha Kiran , Antonchick Andrey P.
Published: March 2018

A combination of readily available and bench‐stable CF3SO2Na and tBuOOH was efficiently used for hydrotrifluoromethylation of alkynes. An excellent trans‐selectivity was demonstrated in the synthesis of alkenes. The developed mild reaction conditions allow the supression of the competing Meyer–Schuster‐type rearrangement.
Quantitative Biodetection of Anticancer Drug Rituxan with DNA Biosensor Modified PAMAM Dendrimer/Reduced Graphene Oxide Nanocomposite
Authors: Hatamluyi Behnaz , Es'haghi Zarrin
Published: March 2018

PAMAM dendrimer/reduced graphene oxide nanocomposite modified pencil graphite electrode (PAMAM/RGO/PGE) was used to fabricate an electrochemical DNA biosensor for determination of Rituxan (RTX) at low concentrations, for the first time. The fabricated biosensor was characterized with FE‐SEM, EIS, and CV techniques. The ds‐DNA/PAMAM/RGO/PGE was used as a working electrode to study the interaction between the RTX and salmon sperm ds‐DNA by DPV technique. Because of the interaction between the drug and DNA leads to a decrease in the guanine oxidation peak current, it was used as an indicator for the determination of the RTX. Under the optimized experimental conditions, a wide linear relationship between RTX concentration and guanine signal was obtained within the range of 7.0 to 60.0 μmol L−1 and 60.0 to 300.0 μmol L−1 with a low detection limit (0.56 μmol L−1). To clarify the interaction mechanism between the RTX and the ds‐DNA, DPV and UV‐Vis measurements were used. The reproducibility, stability, and performance of the constructed biosensor was examined by quantitative measuring RTX in pharmaceutical and human serum samples with good precision (RSD; 2.0–6.0 %) and acceptable recoveries (100.04–101.95 %).
Probing the molecular regulation of lipopolysaccharide stress in piglet liver by comparative proteomics analysis
Authors: Xia Bing , Meng Qingshi , Feng Xiaohui , Tang Xiangfang , Jia Anfeng , Feng Jinghai , Zhang Sheng , Zhang Hongfu
Published: March 2018

Lipopolysaccharide (LPS) can induce inflammatory responses in piglets, causing immunological stress and tissue damage. However, chronic LPS infection may lead to LPS‐induced immunological stress resistance. The molecular mechanisms underlying LPS stress have not been fully elucidated. Here, we conducted a global comparative proteomics analysis to investigate the molecular regulation of LPS stress using an immunological stress model of weaned piglets. A shotgun‐based SWATH‐MS workflow was used for global proteomes of the piglet livers after 15‐day LPS treatment. Out of 3700 quantified proteins, 93 proteins showed differential changes under LPS stress. Bioinformatics analysis indicated that the differentially expressed proteins were mainly involved in inflammatory response, oxidation‐redox processes and defense reactions, and were enriched in a phagosome pathway. Several key proteins associated with oxidative stress (SOD2), inflammation response (STEAP4 and S100 family) and the phagosome pathway were verified by activity and targeted‐MS analyses. The observed responses appear to mitigate hepatic damage due to excessive oxidative stress, inflammation, and repression of the phagosome pathway. Our results reveal that an increased STEAP4 expression in piglets appears involved in cellular regulation by LPS stress and subsequent immunological stress resistance. This study sheds new light on the mechanism of prevention and relieving injury by LPS‐induced immune responses.
Geomorphic response to late Quaternary tectonics in the axial portion of the Southern Apennines (Italy): A case study from the Calore River valley
Authors: Amato V. , Aucelli P.P.C. , Cesarano M. , Filocamo F. , Leone N. , Petrosino P. , Rosskopf C.M. , Valente E. , Casciello E. , Giralt S. , Jicha B.R.
Published: March 2018

The present study focuses on the morphotectonic evolution of the axial portion of the Southern Apennine chain between the lower Calore River valley and the northern Camposauro mountain front (Campania Region). A multidisciplinary approach was used, including geomorphological, field‐geology, stratigraphical, morphotectonic, structural, 40Ar/39Ar and tephrostratigraphical data. Results indicate that, from the Lower Pleistocene onwards, this sector of the chain was affected by extensional tectonics responsible for the onset of the sedimentation of Quaternary fluvial, alluvial fan and slope deposits. Fault systems are mainly composed of NW‐SE, NE–SW and W‐E trending strike‐slip and normal faults, associated to NW‐SE and NE–SW oriented extensions. Fault scarps, stratigraphical and structural data and morphotectonic indicators suggest that these faults affected the wide piedmont area of the northern Camposauro mountain front in the Lower Pleistocene–Upper Pleistocene time span. Faults affected both the oldest Quaternary slope deposits (Laiano Synthem, Lower Pleistocene) and the overlying alluvial fan system deposits constrained between the late Middle Pleistocene and the Holocene. The latter are geomorphologically and chrono‐stratigraphically grouped into four generations, I generation: late Middle Pleistocene–early Upper Pleistocene, with tephra layers 40Ar/39Ar dated to 158±6 and 113±7 ka; II generation: Upper Pleistocene, with tephra layers correlated with the Campanian Ignimbrite (39 ka) and with the slightly older Campi Flegrei activity (40Ar/39Ar age 48±7 ka); III generation: late Upper Pleistocene–Lower Holocene, with tephra layers correlated with the Neapolitan Yellow Tuff (~15 ka); IV generation: Holocene in age. The evolution of the first three generations was controlled by Middle Pleistocene extensional tectonics, while Holocene fans do not show evidence of tectonic activity. Nevertheless, considering the moderate to high magnitude historical seismicity of the study area, we cannot rule out that some of the recognized faults may still be active. Copyright © 2018 John Wiley & Sons, Ltd.
Mineralogical and geochemical characteristics of K‐bentonites from the Late Ordovician to the Early Silurian in South China and their geological significance
Authors: Ge Xiangying , Mou Chuanlong , Wang Chengshan , Men Xin , Chen Chao , Hou Qian
Published: March 2018

There are numerous K‐bentonites interlayered with black shales from the Late Ordovician‐Early Silurian that are widely distributed in South China. In this paper, we carried out mineralogical and geochemical investigations on K‐bentonite samples collected from 6 sections in South China. The petrological features of thin sections, X‐ray diffraction data, and major element results show that in addition to clay minerals, which are dominated by illite/smectite mixed layer and illite, the K‐bentonites also contain quartz, microcline, albite, pyrite, and zircon. Zircon U–Pb dating for two K‐bentonite beds (WXP‐BT2 and LBP‐BT1) by the LA‐ICP‐MS method yielded two weighted mean 206Pb/238U ages of 443.5 ± 1.9 and 440.4 ± 5.6 Ma, respectively. The concentrations of rare earth elements (REEs) range from 141.28 to 854.44 ppm, chondrite‐normalized REE patterns display a negative Eu anomaly and an enhanced enrichment in light REE. Samples plot in the fields of trachyte, trachyandesite, rhyodacite (dacite), and andesite in a plot of Nb/Y against Zr/TiO2 suggest that the K‐bentonites are most probably derived from felsic magmas with subalkaline to alkaline affinities. The discrimination diagrams (Y‐Nb, Y + Ta‐Rb, Y + Nb‐Rb) show that the tectonic setting of the source volcanoes ranges from a volcanic arc to within‐plate setting. The widely distributed bentonites suggest intensified volcanic ash eruptions in the early Late Ordovician, which released huge amounts of volcanic ash. The SO2 emission and the weathering of the volcanic ashes probably resulted in global climate cooling and indirectly caused the Hirnantian glaciation and the mass extinction at the end of the Ordovician Period.
A voxel‐based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients
Authors: Keller Simon S. , Roberts Neil , Baker Gus , Sluming Vanessa , Cezayirli Enis , Mayes Andrew , Eldridge Paul , Marson Anthony G. , Wieshmann Udo C.
Published: March 2018

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole‐brain voxel‐based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty‐four controls were also studied. Right‐handed controls and right‐handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo‐occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right‐handed. These results suggest that structural asymmetries of an insular‐fronto‐temporal network may be related to HLD.
Liver‐enriched transcription factor expression relates to chronic hepatic failure in humans
Authors: Guzman‐Lepe Jorge , Cervantes‐Alvarez Eduardo , Collin de l'Hortet Alexandra , Wang Yang , Mars Wendy M. , Oda Yoshinao , Bekki Yuki , Shimokawa Masahiro , Wang Huanlin , Yoshizumi Tomoharu , Maehara Yoshihiko , Bell Aaron , Fox Ira J. , Takeishi Kazuki , Soto‐Gutierrez Alejandro
Published: March 2018

The mechanisms by which the liver fails in end‐stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver‐enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer‐binding protein (CEBP)α, and CEBPβ. We then selected downstream genes responsible for some hepatic functions (ornithine transcarbamylase [OTC], cytochrome P450 3A4 [CYP3A4], coagulation factor VII [F7], cadherin 1 [CDH1], phospho‐ezrin (Thr567)/radixin (Thr564)/moesin (Thr558) [p‐ERM], phospho‐myosin light chain [p‐MLC], low‐density lipoprotein receptor‐related protein 1 [LRP1]) in liver tissue from patients at different stages of decompensated liver function based upon Child‐Pugh classification, Model for End‐Stage Liver Disease score, and degree of inflammatory activity/fibrosis. We first examined differential expression of LETF and determined whether a relationship exists between transcript and protein expression, and liver function. We found HNF4α expression was down‐regulated and correlated well with the extent of liver dysfunction (P = 0.001), stage of fibrosis (P = 0.0005), and serum levels of total bilirubin (P = 0.009; r = 0.35), albumin (P < 0.001; r = 0.52), and prothrombin time activity (P = 0.002; r = 0.41). HNF4α expression also correlated with CYP3A4, OTC, and F7 as well as CDH1 RNA levels. The Rho/Rho‐associated protein kinase pathways, which have been implicated in the regulation of HNF4α, were also differentially expressed, in concert with LRP1, a reported upstream regulator of RhoA function. Conclusion: HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. (Hepatology Communications 2018;2:582‐594)
Expanding the work–life balance discourse to LGBT employees: Proposed research framework and organizational responses
Authors: Stavrou Eleni , Ierodiakonou Christiana
Published: March 2018

Relying on a gender neutrality rhetoric, the work–life balance (WLB) discourse has challenged gendered roles, but has failed to expand “gender neutrality” to aspects of gender identity and sexual orientation. In turn, WLB research has systematically excluded lesbian, gay, bisexual, and transgender (LGBT) employees. We build on stakeholder theory and the resource‐based view of the firm to propose extending the WLB discourse and associated policies and practices to LGBT employees as key internal stakeholders who can possibly contribute to organizational performance, either directly or indirectly. We further combine these perspectives with institutional theory in an integrative research framework that relies on the critical realist structured ontology and denotes the institutional embeddedness of organizations. Adopting this institutional perspective, we propose that explanations regarding the adoption of LGBT WLB policies in organizations go beyond the organizational level to include higher level institutional characteristics. Similarly, we posit that the relationship between LGBT WLB policies and organizational performance outcomes is influenced by such characteristics. Drawing from this framework, we put forth a typology of organizational responses that postulates the possible outcomes for organizations given their re(actions) to institutional pressures and their attitude toward LGBT employees as stakeholders.
Four‐Variable Model of an Enzymatic Oscillator Based on Trypsin
Authors: Semenov Sergey N. , Ainla Alar , Skorb Ekaterina V. , Postma Sjoerd G. J.
Published: March 2018

This paper describes a four‐variable model for an enzymatic oscillator based on trypsin. Variables in this model are concentrations of the essential proteins (trypsin and trypsinogen) and small molecules (masked and active inhibitors of trypsin) within the network. Importantly, to simplify the model, non‐essential side reactions are neglected and essential reactions are assumed to follow first or second order kinetics. Numerical solutions of this reduced model semi‐quantitatively reproduce experimentally determined periods, amplitudes, and phase shifts of oscillations in the concentrations of several species in the network. Moreover, linear stability analysis shows that oscillations in the trypsin oscillator emerge and disappear through Hopf bifurcation. The model will be helpful in situations where simplicity is necessary such as detailed analysis of dynamics and modeling of reaction‐diffusion systems.
Mesenchymal stem cell seeded, biomimetic 3D printed scaffolds induce complete bridging of femoral critical sized defects
Authors: Szivek John A. , Gonzales David A. , Wojtanowski Andrew M. , Martinez Michael A. , Smith Jordan L.
Published: March 2018

No current clinical treatments provide an ideal long‐term solution for repair of long bone segment defects. Incomplete healing prevents patients from returning to preinjury activity and ultimately requires additional surgery to induce healing. Obtaining autologous graft material is costly, incurs morbidity, requires surgical time, and quality material is finite. In this pilot study, 3D printed biomimetic scaffolds were used to facilitate rapid bone bridging in critical sized defects in a sheep model. An inverse trabecular pattern based on micro‐CT scans of sheep trabecular bone was printed in polybutylene terephthalate. Scaffolds were coated with micron‐sized tricalcium phosphate particles to induce osteoconductivity. Mesenchymal stem cells (MSCs) were isolated from sheep inguinal and tail fat, in one group of sheep and scaffolds were infiltrated with MSCs in a bioreactor. Controls did not undergo surgery for cell extraction. Scaffolds were implanted into two experimental and two control adult sheep, and followed for either 3 or 6 months. Monthly radiographs and post explant micro‐CT scanning demonstrated bone formation on the lateral, anterior, medial, and posterior‐medial aspects along the entire length of the defect. Bone formation was absent on the posterior‐lateral aspect where a muscle is generally attached to the bone. The 3‐month time point showed 15.5% more cortical bone deposition around the scaffold circumference while the 6‐month time point showed 40.9% more bone deposition within scaffold pores. Control sheep failed to unite. Serum collagen type‐1C‐terminus telopeptides (CTX‐1) showed time‐dependent levels of bone resorption, and calcein labeling demonstrated an increase in bone formation rate in treated animals compared with controls. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 242–252, 2019.
Impact of apheresis automation on procedure quality and predictability of CD34+ cell yield
Authors: Besson Nelly , Topholm Bruun Mie , Stauffer Larsen Thomas , Nielsen Christian
Published: March 2018

Success of peripheral blood stem cell (PBSC) collections depends on patient biological parameters and stable apheresis device performance. We investigated product quality and factors influencing main apheresis procedure outcomes including CD34+ collection efficiency (CE), product volume or platelet CE. We also assessed different CD34+ cell yield prediction algorithms. Autologous PBSC collections by Spectra Optia from myeloma and lymphoma patients were analyzed. Complete blood count (CBC) from patient preprocedure and from collected products were assessed. (1) Product yield was calculated, (2) Product CBC was correlated with patient preprocedure variables, and (3) Predictions of CD34+ yields based on (a) product CD34+ cell concentration in samples after two or four chamber flushes or (b) traditional CE2 benchmark, were compared. 62 procedures in 41 patients were analyzed. 84% of all procedures were run without operator intervention. Median CD34+ CE2 was 56.9% (48.8%‐65.2%) and quite stable irrespective of patient conditions, with minor influence from patient white blood cell (WBC) precounts (rs = –.47; P < .001). Platelet loss correlated with WBC precount (rs = .46; P < .001), product volume (rs = .71; P < .0001) and number of chambers collected (rs = .72; P < .0001). CD34+ cell yield was better predicted based on (a) product CD34+ cell concentration from samples after 2 and 4 chamber flushes, respectively (rs = .969; P < .0001 and rs = .9648; P < .0001) than based on (b) CE2 formula (rs = .8262, P < .0001). Spectra Optia provides good quality PBSC products with stable and predictable yield regardless of starting conditions. CD34+ sampling of product after few chamber flushes could be used to predict CD34+ yield.
Exposing migratory sparrows to Plasmodium suggests costs of resistance, not necessarily of infection itself
Authors: Kelly Tosha Ruth , Bonner Simon Joseph , MacDougall‐Shackleton Scott A. , MacDougall‐Shackleton Elizabeth A.
Published: March 2018

Migratory birds move through multiple habitats and encounter a diverse suite of parasites. This raises concern over migrants’ role in transporting infectious disease between breeding and wintering grounds, and along migratory flyways. Trade‐offs between flight and immune defenses could interfere with infected individuals’ migratory timing and success, potentially affecting infection dynamics. However, experimental evidence that parasitic infection affects migratory preparation or timing remains scant. We hypothesized that birds encountering hematozoan parasites shortly before migration incur physical costs (reduced body condition) and behavioral costs (delayed migration), due to the infection itself and/or to the demands of mounting an immune response. We experimentally inoculated song sparrows (Melospiza melodia) with Plasmodium shortly before fall migration. We monitored infection and body composition for 2 weeks after inoculation, and used radiotelemetry to track timing of migratory departure for another 7 weeks after release. Inoculated individuals that resisted infection had lower lean mass 12 days post exposure, relative to controls and infected individuals. This suggests trade‐offs between body composition and immune defenses that might reduce migration success of resistant individuals. Despite group differences in body composition prior to release, we did not detect significant differences in timing of migration departure several weeks later. Thus, malarial infection did not appear to incur detectable costs to body composition or to migratory timing, at least when exposure occurs several weeks before migration. This study is novel considering not only the costs of infection, but also the costs of resisting infection, in an experimental context.
The prevalence of anemia in Japanese Universiade athletes, detected with longitudinal preparticipation medical examinations
Authors: Komatsu Takayuki , Yamasawa Fumihiro , Dohi Michiko , Akama Takao , Masujima Atsushi , Kono Ichiro , Kawahara Takashi
Published: March 2018

Background

No reports have evaluated the long‐term trends of the prevalence of anemia in Universiade athletes using preparticipation medical examinations (PPMEs). We aimed to investigate the prevalence of anemia among Japanese Universiade athletes, using longitudinal PPMEs.

Methods

In this retrospective, observational study, athletes with published data from official reports of the Japanese delegation of the summer Universiade games between 1977 and 2011 were included, as were similar‐aged nonathletes with published health data, extracted from official national reports from the Japanese Ministry of Health, Labour and Welfare. PPME data and national health survey data included blood tests for anemia and the age of each participant. We compared the anemia prevalence in both groups using an unpaired t test.

Results

Anemia prevalence among Universiade athletes decreased by 11.6% over the study period (13.3% in 1977 to 1.7% in 2011). Moreover, anemia prevalence between 1991 and 2011 in the total Universiade athlete population was significantly lower than that in the nonathletic population (mean ± standard deviation: 5.2 ± 2.9% vs 9.8 ± 1.5%, respectively; P = .025). In female Universiade athletes, anemia prevalence between 1977 and 1981 was higher than that in the nonathletic populations (48.1% vs 19.7%, respectively). However, in 2003, this value was lower than that in nonathletic female populations (8.5% vs 19.8%, respectively).

Conclusions

A decrease in anemia prevalence in Japanese Universiade athletes was revealed with longitudinal PPMEs. Hematological parameters should be evaluated longitudinally in athletes to provide continuous performance support throughout the athlete's career.
Frog tendon structure and its relationship with locomotor modes
Authors: Abdala Virginia , Ponssa María Laura , Tulli María José , Fabre Anne‐Claire , Herrel Anthony
Published: March 2018

Tendon collagen fibrils are the basic force‐transmitting units of the tendon. Yet, surprisingly little is known about the diversity in tendon anatomy and ultrastructure, and the possible relationships between this diversity and locomotor modes utilized. Our main objectives were to investigate: (a) the ultra‐structural anatomy of the tendons in the digits of frogs; (b) the diversity of collagen fibril diameters across frogs with different locomotor modes; (c) the relationship between morphology, as expressed by the morphology of collagen fibrils and tendons, and locomotor modes. To assess the relationship between morphology and the locomotor modes of the sampled taxa we performed a principal component analysis considering body length, fibrillar cross sectional area (CSA) and tendon CSA. A MANOVA showed that differences between species with different locomotor modes were significant with collagen fibril diameter being the discriminating factor. Overall, our data related the greatest collagen fibril diameter to the most demanding locomotor modes, conversely, the smallest collagen fibril CSA and the highest tendon CSA were observed in animals showing a hopping locomotion requiring likely little absorption of landing forces given the short jump distances.