bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron‐Catalyzed Reaction of Urea with Alcohols and Amines: A Safe Alternative for the Synthesis of Primary Carbamates
Authors: Peña‐López Miguel , Neumann Helfried , Beller Matthias
Published: July 2016

A general study of the iron‐catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N‐unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamate), without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono‐ and disubstituted ureas via selective transamidation reaction. These atom‐economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis‐acidic iron(II) catalyst.
Gyrokinetic Simulations of the Tokamak Plasma Edge in Circular Limiter Configuration
Authors: Korpilo T. , Kiviniemi T. P. , Leerink S. , Niskala P. , Rochford R.
Published: July 2016

The full‐f gyrokinetic code ELMFIRE is used to simulate the impact of turbulent tokamak plasma transport on the edge plasma flow and scrape‐off‐layer width. The simulation is performed in the circular limiter configuration and extends from the magnetic axis to the material surface. The results show that the sheath potential and parallel Mach number are in agreement with theoretical predictions, while the E × B dynamics are strongly affected by the sheath boundary. The radial fall‐off of density and temperature profiles show non‐exponential behaviour in the scrape‐off‐layer. Numerical issues appearing in the ELMFIRE simulation of edge plasma transport are discussed. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study
Authors: Lustenberger Caroline , Mouthon Anne‐Laure , Tesler Noemi , Kurth Salome , Ringli Maya , Buchmann Andreas , Jenni Oskar G. , Huber Reto
Published: July 2016

Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG‐derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high‐density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait‐like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence.
Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I‐NBOMe and 25I‐NBOH
Authors: Nielsen Line Marie , Holm Niels Bjerre , Leth‐Petersen Sebastian , Kristensen Jesper Langgaard , Olsen Lars , Linnet Kristian
Published: July 2016

The dimethoxyphenyl‐N‐((2‐methoxyphenyl)methyl)ethanamine (NBOMe) compounds are potent serotonin 5‐HT2A receptor agonists and have recently been subject to recreational use due to their hallucinogenic effects. Use of NBOMe compounds has been known since 2011, and several non‐fatal and fatal intoxication cases have been reported in the scientific literature. The aim of this study was to determine the importance of the different cytochrome P450 enzymes (CYP) involved in the metabolism of 2‐(4‐iodo‐2,5‐dimethoxyphenyl)‐N‐(2methoxybenzyl)ethanamine (25I‐NBOMe) and 2‐[[2‐(4‐iodo‐2,5dimethoxyphenyl)ethylamino]methyl]phenol (25I‐NBOH) and to characterize the metabolites. The following approaches were used to identify the main enzymes involved in primary metabolism: incubation with a panel of CYP and monoamine oxidase (MAO) enzymes and incubation in pooled human liver microsomes (HLM) with and without specific CYP chemical inhibitors. The study was further substantiated by an evaluation of 25I‐NBOMe and 25I‐NBOH metabolism in single donor HLM. The metabolism pathways of 25I‐NBOMe and 25I‐NBOH were NADPHdependent with intrinsic clearance values of (CLint) of 70.1 and 118.7 mL/min/kg, respectively. The biotransformations included hydroxylation, O‐demethylation, N‐dealkylation, dehydrogenation, and combinations thereof. The most abundant metabolites were all identified by retention time and spectrum matching with synthesized reference standards. The major CYP enzymes involved in the metabolism of 25I‐NBOMe and 25INBOH were identified as CYP3A4 and CYP2D6, respectively. The compound 25I‐NBOH was also liable to direct glucuronidation, which may diminish the impact of CYP2D6 genetic polymorphism. Users of 25I‐NBOMe may be subject to drug‐drug interactions (DDI) if 25I‐NBOMe is taken with a strong CYP3A4 inhibitor. Copyright © 2016 John Wiley & Sons, Ltd.
Reintroduction of rare arable plants by seed transfer. What are the optimal sowing rates?
Authors: Lang Marion , Prestele Julia , Fischer Christina , Kollmann Johannes , Albrecht Harald
Published: July 2016

During the past decades, agro‐biodiversity has markedly declined and some species are close to extinction in large parts of Europe. Reintroduction of rare arable plant species in suitable habitats could counteract this negative trend. The study investigates optimal sowing rates of three endangered species (Legousia speculum‐veneris (L.) Chaix, Consolida regalis Gray, and Lithospermum arvense L.), in terms of establishment success, seed production, and crop yield losses.

A field experiment with partial additive design was performed in an organically managed winter rye stand with study species added in ten sowing rates of 5–10,000 seeds m−2. They were sown as a single species or as a three‐species mixture (pure vs. mixed sowing) and with vs. without removal of spontaneous weeds. Winter rye was sown at a fixed rate of 350 grains m−2. Performance of the study species was assessed as plant establishment and seed production. Crop response was determined as grain yield.

Plant numbers and seed production were significantly affected by the sowing rate, but not by sowing type (pure vs. mixed sowing of the three study species), and weed removal. All rare arable plant species established and reproduced at sowing rates >25 seeds m−2, with best performance of L. speculum‐veneris. Negative density effects occurred to some extent for plant establishment and more markedly for seed production.

The impact of the three study species on crop yield followed sigmoidal functions. Depending on the species, a yield loss of 10% occurred at >100 seeds m−2.

Synthesis and applications: The study shows that reintroduction of rare arable plants by seed transfer is a suitable method to establish them on extensively managed fields, for example, in organic farms with low nutrient level and without mechanical weed control. Sowing rates of 100 seeds m−2 for C. regalis and L. arvense, and 50 seeds m−2 for L. speculum‐veneris are recommended, to achieve successful establishment with negligible crop yield losses.
Harnessing fishery‐independent indicators to aid management of data‐poor fisheries: weighing habitat and fishing effects
Authors: Nash Kirsty L. , Bijoux Jude , Robinson Jan , Wilson Shaun K. , Graham Nicholas A. J.
Published: July 2016

State indicators, e.g., mean size and trophic level of the fish assemblage, can provide important insights into the effects of fishing on ecosystems and the resource potential of the fishery. On coral reefs, few studies have examined the relative effects of fishing and other drivers, such as habitat, on these indicators. In light of habitat heterogeneity and increasing habitat degradation, this lack of understanding limits the usefulness of indicators for monitoring the effect of fishery management actions. Identifying thresholds or nonlinearities in relationships between fishing pressure and state indicators has been suggested as a basis for biomass‐based targets to support management efforts in low research capacity contexts. Using data collected in Seychelles, we examined the relative influences of fishable biomass (proxy for fishing pressure) and the benthic habitat on fisheries‐independent indicators characterizing attributes of the fish community important for fisheries production. We characterized the driver–indicator relationships, and compared local‐scale relationships for Seychelles with large‐scale relationships published for the Indian Ocean. We found that both habitat and fishing pressure influenced indicators, but habitat effects were particularly strong. This knowledge provides managers with the capacity to implement a diverse array of complementary management actions targeting these drivers. A number of the Seychelles scale driver–indicator relationships were linear, suggesting gradual changes in indicators in response to changes to drivers. This contrasted with relationships published for the Indian Ocean, which were characterized by thresholds below which exploitation is likely to have significant detrimental effects on the functioning of important ecosystem processes. These scale‐specific differences are likely driven by the narrower range of fishing pressures found in Seychelles. Importantly, it indicates that, although biomass‐based targets derived from large‐scale relationships may provide a useful starting point for setting management targets, the local context must be considered.
CD28 days later: Resurrecting costimulation for CD8+ memory T cells
Authors: van der Heide Verena , Homann Dirk
Published: July 2016

Rapid activation and proliferative expansion of specific CD8+ memory T (CD8+TM) cells upon antigen re‐encounter is a critical component of the adaptive immune response that confers enhanced immune protection. In this context, however, the requirements for costimulation in general, and CD28 signaling in particular, remain incompletely defined. In the current issue of the European Journal of Immunology, Fröhlich et al. [Eur. J. Immunol. 2016. 46: 1644‐1655] provide definitive evidence that optimal elaboration of CD8+TM‐cell recall responses is indeed contingent on CD28 expressed by these cells. Here, we discuss the “CD28 costimulation paradigm” in its historical context and highlight some of the unresolved complexities pertaining to CD28‐dependent interactions that shape CD8+ T‐cell phenotypes, functionalities, and recall reactivity.
Application of Imidazole‐2‐thione Substituents in Low‐Coordinate Phosphorus Chemistry – Probing the Scope
Authors: Majhi Paresh Kumar , Koner Abhishek , Schnakenburg Gregor , Kelemen Zsolt , Nyulászi László , Streubel Rainer
Published: July 2016

A variety of (2‐thioxoimidazol‐4‐yl)phosphanes have been synthesized with the prospect of further functionalization. Following a standard reaction protocol, P‐amino (2a,b), P‐chloro (3a,b), and P‐hydrogeno (8a) phosphane derivatives were synthesized. Treatment of chlorophosphanes 3a,b with Lewis acids in dichloromethane/diethyl ether did not afford the expected phosphenium cation, instead ethoxyphosphane derivatives 5a,b were isolated. Treatment of secondary phosphane 8a with potassium hexamethyldisilazide afforded 2‐thioxoimidazol‐4‐yl‐substituted phosphanide derivative 10a, which was used to access dinuclear phosphanido borane 11a and tungsten complexes 12a. Furthermore, the first strong NMR evidence for P‐anionic bis(imidazole‐2‐ylidene) 13a is provided. The first attempts to synthesize an (2‐thioxoimidazol‐4‐yl)‐substituted phosphanyl radical or its dimer, the tetrakis(2‐thioxoimidazol‐4‐yl)‐substituted diphosphane, led exclusively to tris(2‐thioxoimidazole‐4‐yl)phosphane 14a. These compounds were fully characterized spectroscopically and the structures of 2a, 3a, 7b, 8a, 10a, 11a, and 14a were determined by single‐crystal X‐ray crystallography. The challenges associated with the synthesis of some of the titled compounds were studied computationally.
Thermally Cross‐Linkable Host Materials for Solution‐Processed OLEDs: Synthesis, Characterization, and Optoelectronic Properties
Authors: Tang Yuanju , Zhuang Jinyong , Xie Liming , Chen Xiaolian , Zhang Dongyu , Hao Jian , Su Wenming , Cui Zheng
Published: July 2016

A series of cross‐linkable bipolar host materials containing carbazole (donor, D) and 1,2,4‐triazole (acceptor, A) were designed and synthesized. The host materials with styryl groups can be thermally cross‐linked by curing at 172–190 °C without any polymerization initiator. Excellent solvent resistance was observed for all the host materials, which is beneficial for the preparation of subsequent functional layers by solution processes. The highest occupied molecular orbital energy levels of 5.55, 5.58 and 5.54 eV are estimated for these host materials, which indicates low injection barrier from the hole transport layer. A current efficiency of 15.3 cd A–1 and an external quantum efficiency of 4.6 % were achieved for solution‐processed Ir(mppy)3‐based OLEDs by using the cross‐linkable host material.
Serendipitous Synthesis of (tert‐Butyl‐NNO‐azoxy)acetonitrile: Reduction of an Oxime Moiety to a Methylene Unit
Authors: Klenov Michael S. , Anikin Oleg V. , Guskov Alexey A. , Churakov Aleksandr M. , Strelenko Yurii A. , Ananyev Ivan V. , Bushmarinov Ivan S. , Dmitrienko Artem O. , Lyssenko Konstantin A. , Tartakovsky Vladimir A.
Published: July 2016

(tert‐Butyl‐NNO‐azoxy)acetonitrile (1) is a useful precursor for a number of nitrogen heterocycles. It was found that it could be obtained in good yield by treatment of the salts of (tert‐butyl‐NNO‐azoxy)(hydroxyimino)acetonitrile with NH2OTs. It is the first case of one‐step reduction of an oxime group to a methylene unit using an aminating agent. A plausible reaction mechanism is proposed. In addition, a new strategy for the tetrazole 1‐oxide ring construction was developed. This involves a diazo‐group transfer to the active‐methylene unit of compound1, followed by intramolecular coupling of the azoxy and diazo groups. The tetrazole structures were confirmed by X‐ray diffraction analysis.
Catalytic Conversion of Furan to Hydrocarbons using HZSM‐5: Coking Behavior and Kinetic Modeling including Coke Deposition
Authors: Shao Shanshan , Zhang Huiyan , Xiao Rui , Shen Dekui
Published: July 2016

Coke deposition is the biggest barrier that hinders the hydrocarbon yields during the catalytic pyrolysis of biomass. The proposed pathway studied here yields benzofuran as a primary product, all the olefins and aromatic hydrocarbons as secondary products, and polycyclic aromatic hydrocarbons as tertiary products. The product selectivity only changed with catalytic temperature and coke deposition, whereas no effect was observed if the weight hourly space velocity and partial pressure were varied. The curve of conversion versus coke content in the catalytic conversion of furan follows an exponential trend [i.e., Φ=exp(‐αC)] which indicates that the catalytic conversion of furan exhibits fast deactivation. A kinetic model considering coke deposition has been built based on the above reaction pathway to correlate the product distribution with the coke content, and the final correlation coefficients (>0.96) indicate good agreement.
Thermocatalytic Reforming of Biomass Waste Streams
Authors: Conti Roberto , Jäger Nils , Neumann Johannes , Apfelbacher Andreas , Daschner Robert , Hornung Andreas
Published: July 2016

A thermocatalytic reforming (TCR®) unit patented by Fraunhofer UMSICHT was tested to convert lignocellulosic biomass and three organic wastes, digestate, paper sludge, and sewage sludge, into enhanced pyrolysis products. The TCR® reactor is an intermediate pyrolysis screw reactor connected to a reformer. hawse have explored the TCR® of four feedstocks in a 2 kg h−1 laboratory‐scale plant. The aim of the work was to compare the product yields and qualities (biochar, bio‐oil, and syngas) obtained by using TCR® under the same pyrolysis conditions (pyrolysis at 400 °C and postcatalytic reforming at 700 °C). Finally, paper sludge bio‐oil was distilled at several temperatures to obtain the oil fractions. High‐quality bio‐oil and syngas from four different kinds of biomass were obtained and compared to that from traditional intermediate pyrolysis and fast pyrolysis. The bio‐oil showed a high higher heating value (HHV) (35–38 MJ kg−1) independent of the kind of biomass used, and the total acid number was 1.8–5.4 mgKOH g−1. Fractional distillation led to a gasoline‐like light fraction and an overall distillation rate of 74 %.
Novel fusion genes and chimeric transcripts in ependymal tumors
Authors: Olsen Thale Kristin , Panagopoulos Ioannis , Gorunova Ludmila , Micci Francesca , Andersen Kristin , Kilen Andersen Hege , Meling Torstein R. , Due‐Tønnessen Bernt , Scheie David , Heim Sverre , Brandal Petter
Published: July 2016

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA‐sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST‐like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus‐specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA‐seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4‐CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.
Preserved white matter microstructure in young patients with anorexia nervosa?
Authors: Pfuhl Gerit , King Joseph A. , Geisler Daniel , Roschinski Benjamin , Ritschel Franziska , Seidel Maria , Bernardoni Fabio , Müller Dirk K. , White Tonya , Roessner Veit , Ehrlich Stefan
Published: July 2016

A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1‐weighted and diffusion‐weighted MRI data in a sizable sample of young and medication‐free acAN (n = 35), recAN (n = 32), and age‐matched female healthy controls (HC, n = 62) were obtained. For analysis, a well‐validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non‐chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069–4083, 2016. © 2016 Wiley Periodicals, Inc.
Longitudinal changes in functional connectivity of cortico‐basal ganglia networks in manifests and premanifest huntington's disease
Authors: Gargouri Fatma , Messé Arnaud , Perlbarg Vincent , Valabregue Romain , McColgan Peter , Yahia‐Cherif Lydia , Fernandez‐Vidal Sara , Ben Hamida Ahmed , Benali Habib , Tabrizi Sarah , Durr Alexandra , Lehéricy Stéphane
Published: July 2016

Huntington's disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico‐basal ganglia networks. We acquired structural MRI and resting‐state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender‐ and age‐matched healthy volunteers from the TRACK‐HD study. We inferred topological changes in functional connectivity between 182 regions within cortico‐basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp 37:4112–4128, 2016. © 2016 Wiley Periodicals, Inc.
The impact of parkinson's disease on the cortical mechanisms that support auditory–motor integration for voice control
Authors: Huang Xiyan , Chen Xi , Yan Nan , Jones Jeffery A. , Wang Emily Q. , Chen Ling , Guo Zhiqiang , Li Weifeng , Liu Peng , Liu Hanjun
Published: July 2016

Several studies have shown sensorimotor deficits in speech processing in individuals with idiopathic Parkinson's disease (PD). The underlying neural mechanisms, however, remain poorly understood. In the present event‐related potential (ERP) study, 18 individuals with PD and 18 healthy controls were exposed to frequency‐altered feedback (FAF) while producing a sustained vowel and listening to the playback of their own voice. Behavioral results revealed that individuals with PD produced significantly larger vocal compensation for pitch feedback errors than healthy controls, and exhibited a significant positive correlation between the magnitude of their vocal responses and the variability of their unaltered vocal pitch. At the cortical level, larger P2 responses were observed for individuals with PD compared with healthy controls during active vocalization due to left‐lateralized enhanced activity in the superior and inferior frontal gyrus, premotor cortex, inferior parietal lobule, and superior temporal gyrus. These two groups did not differ, however, when they passively listened to the playback of their own voice. Individuals with PD also exhibited larger P2 responses during active vocalization when compared with passive listening due to enhanced activity in the inferior frontal gyrus, precental gyrus, postcentral gyrus, and middle temporal gyrus. This enhancement effect, however, was not observed for healthy controls. These findings provide neural evidence for the abnormal auditory–vocal integration for voice control in individuals with PD, which may be caused by their deficits in the detection and correction of errors in voice auditory feedback. Hum Brain Mapp 37:4248–4261, 2016. © 2016 Wiley Periodicals, Inc.
Allelopathic Activity of the Iron Chelator Anachelin – A Molecular Hybrid with a Dual Mode of Action
Authors: De Sarkar Suman , Blom Judith F. , Bethuel Yann , Jüttner Friedrich , Gademann Karl
Published: July 2016

One of the compounds suggested to be responsible for the cyanobacterial dominance over competing green algae is identified. Evidence is provided on the molecular, chemical level that the iron chelator anachelin from the cyanobacterium Anabaena cylindrica promotes both the growth of cyanobacteria and reduces the growth of competing chlorophytes. These results illustrate a molecular strategy of addressing two challenges (nutrient availability and algal competition) by one molecule. Such strategies could be implied in harmful algal blooms in marine and freshwater environments.
Ruthenium Lewis Acid‐Catalyzed Asymmetric Diels–Alder Reactions: Reverse‐Face Selectivity for α,β‐Unsaturated Aldehydes and Ketones
Authors: Thamapipol Sirinporn , Ludwig Bettina , Besnard Céline , Saudan Christophe , Kündig E. Peter
Published: July 2016

Acrolein, methacrolein, methyl vinyl ketone, ethyl vinyl ketone, 3‐methyl‐3‐en‐2‐one, and divinyl ketone were coordinated to a cationic cyclopentadienyl ruthenium(II) Lewis acid incorporating the electron‐poor bidentate BIPHOP–F ligand. Analysis by NOESY and ROESY NMR techniques allowed the determination of conformations of enals and enones present in solution in CD2Cl2. The results were compared to solid‐state structures and to the facial selectivities of catalytic asymmetric Diels–Alder reactions with cyclopentadiene. X‐Ray structures of four Ru‐enal and Ru‐enone complexes show the α,β‐unsaturated C=O compounds to adopt an anti‐s‐trans conformation. In solution, enals assume both anti‐s‐trans and anti‐s‐cis conformations. An additional conformation, syn‐s‐trans, is present in enone complexes. Enantioface selectivity in the cycloaddition reactions differs for enals and enones. Reaction products indicate enals to react exclusively in the anti‐s‐trans conformation, whereas with enones, the major product results from the syn‐s‐trans conformation. The alkene in s‐cis conformations, while present in solution, is shielded and cannot undergo cycloaddition. A syn‐s‐trans conformation is found in the solid state of the bulky 6,6‐dimethyl cyclohexanone‐Ru(II) complex. The X‐ray structure of divinyl ketone is unique in that the Ru(II) center binds the enone via a η2 bond to one of the alkene moieties. In solution, coordination to Ru–C=O oxygen is adopted. A comparison of facial preference is also made to the corresponding indenyl Lewis acids.
Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia
Authors: Chisini Marta , Stefanizzi Caterina , Ceglie Teresa , Raponi Sara , Vozella Federico , Colafigli Gioia , Salaroli Adriano , D'Angiò Mariella , Mancini Marco , Diverio Daniela , Breccia Massimo , Mancini Francesca , Minotti Clara , Trisolini Silvia , Capria Saveria , Testi Anna Maria , Guarini Anna , Latagliata Roberto , De Propris Maria Stefania , Foà Robin
Published: July 2016

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9‐81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6‐176.0), with 2‐year disease‐free survival rate of 45.1% (95% confidence interval 39.6‐50.6). The median overall survival was 14.4 months (range 0.3‐177.0), with 2‐year overall survival rate of 42.2% (95% confidence interval 37.5‐46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low‐risk karyotype (P < .001), no high‐risk karyotype (P = .006), positivity for AML‐ETO (P = .004)/CBFβ‐MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3‐ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 109/L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 109/L (P = .017), and low‐risk/no high‐risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.
An Overview on Predictive Biomarkers of Testicular Germ Cell Tumors
Authors: Chieffi Paolo
Published: July 2016

Testicular germ cell tumors (TGCTs) are frequent solid malignant tumors and cause of death in men between 20–40 years of age. Genetic and environmental factors play an important role in the origin and development of TGCTs. Although the majority of TGCTs are responsive to chemotherapy, about 20% of patient presents incomplete response or tumors relapse. In addition, the current treatments cause acute toxicity and several chronic collateral effects, including sterility. The present mini‐review collectively summarize the most recent findings on the new discovered molecular biomarkers such as tyrosine kinases, HMGAs, Aurora B kinase, and GPR30 receptor predictive of TGCTs and as emerging new possible molecular targets for therapeutic strategies. J. Cell. Physiol. 232: 276–280, 2017. © 2016 Wiley Periodicals, Inc.
Atrogin‐1 Increases Smooth Muscle Contractility Through Myocardin Degradation
Authors: Singh Pavneet , Li Dong , Gui Yu , Zheng Xi‐Long
Published: July 2016

Atrogin‐1, an E3 ligase present in skeletal, cardiac and smooth muscle, down‐regulates myocardin protein during skeletal muscle differentiation. Myocardin, the master regulator of smooth muscle cell (SMC) differentiation, induces expression of smooth muscle marker genes through its association with serum response factor (SRF), which binds to the CArG box in the promoter. Myocardin undergoes ubiquitylation and proteasomal degradation. Evidence suggests that proteasomal degradation of myocardin is critical for myocardin to exert its transcriptional activity, but there is no report about the E3 ligase responsible for myocardin ubiquitylation and subsequent transactivation. Here, we showed that overexpression of atrogin‐1 increased contractility of cultured SMCs and mouse aortic tissues in organ culture. Overexpression of dominant‐negative myocardin attenuated the increase in SMC contractility induced by atrogin‐1. Atrogin‐1 overexpression increased expression of the SM contractile markers while downregulated expression of myocardin protein but not mRNA. Atrogin‐1 also ubiquitylated myocardin for proteasomal degradation in vascular SMCs. Deletion studies showed that atrogin‐1 directly interacted with myocardin through its amino acids 284–345. Immunostaining studies showed nuclear localization of atrogin‐1, myocardin, and the Rpt6 subunit of the 26S proteasome. Atrogin‐1 overexpression not only resulted in degradation of myocardin but also increased recruitment of RNA Polymerase II onto the promoters of myocardin target genes. In summary, our results have revealed the roles for atrogin‐1 in the regulation of smooth muscle contractility through enhancement of myocardin ubiquitylation/degradation and its transcriptional activity. J. Cell. Physiol. 232: 806–817, 2017. © 2016 Wiley Periodicals, Inc.
Vimentin as a Marker of Early Differentiating, Highly Motile Corneal Epithelial Cells
Authors: Castro‐Muñozledo Federico , Meza‐Aguilar Diana G. , Domínguez‐Castillo Rocío , Hernández‐Zequinely Veremundo , Sánchez‐Guzmán Erika
Published: July 2016

Vimentin (Vim), a cytoskeletal intermediate filament, is part of a naturally occurring reversible program, the Epithelial‐Mesenchymal Transition (EMT), which converts epithelial cells into mesenchymal‐like derivatives. Based on previous results showing that epithelial cells co‐express Vim and keratin (Krt) as part of a cytoskeletal network which confers them a highly motile phenotype, we explored the role of Vim in rabbit corneal epithelial cells or RCE1(5T5) cells, an established model of corneal epithelial differentiation. Vim and keratin filaments were co‐expressed in cells localized at the proliferative/migratory rim of the growing colonies, but not in basal cells from the center of the colonies nor at suprabasal cell layers. Flow cytometry and qPCR demonstrated that there was a decrease in Krt+/Vim+ cell number and ΔNp63α expression when cells reached confluence and formed a 4–5 layered epithelium, while there was a concomitant increase of both Pax‐6 expression and Krt+/Vim− cells. Inhibition of cell proliferation with mitomycin C did not modify cell motility nor the expression of Vim. We studied the distribution and expression of α6 integrin, a protein also involved in cell migration. The results demonstrated that α6 integrin had a distribution which was, in part, co‐linear with Vim at the proliferative/migratory rim of cell colonies, suggesting an indirect interaction between these proteins. Immunoprecipitation and immunostaining assays indicated that plectin might be mediating such interaction. These data suggest that Vim expression in corneal epithelium is found in a cell population composed of highly motile cells with a Vim+/Krt+/ΔNp63α+/Pax‐6low/α6 integrin+ phenotype. J. Cell. Physiol. 232: 818–830, 2017. © 2016 Wiley Periodicals, Inc.
Concurrent nonindependent fixed‐ratio schedules of alcohol self‐administration: Effects of schedule size on choice
Authors: Meisch Richard A. , Gomez Thomas H.
Published: July 2016

Choice behavior was studied under concurrent nonindependent fixed‐ratio fixed‐ratio (nFR) schedules of reinforcement, as these schedules result in frequent changeover responses. With these schedules, responses on either operandum count toward the completion of the ratio requirements of both schedules. Five monkeys were subjects, and two pairs of liquid reinforcers were concurrently available: 16% (w/v) and 0% ethanol or 16% and 8% ethanol. For each pair of reinforcers, the nFR sizes were systematically altered across sessions while keeping the schedule size equal for both liquids. Responding varied as a function of reinforcer pair and nFR size. With the 16% and 0% pair, higher response rates were maintained by 16% and were an inverted U‐shape function of nFR size. With 16% and 8%, a greater number of responses initially occurred on the schedule that delivered 8% ethanol. However, as nFR size increased, preference reversed such that responses that delivered 16% ethanol were greater. When the nFR size was subsequently decreased, preference reverted back to 8%. Number of responses emitted per delivery was a dependent variable and, in behavioral economic terms, was the price paid for each liquid delivery. With 16% and 0%, changeover responses initially increased and then decreased as schedule size became larger. In contrast, with the 16% and 8% pair, changeover responses increased directly with schedule size. Responding under nFR schedules is sensitive to differences in reinforcer magnitude and demonstrates that relative reinforcing effects can change as a function of schedule size.
Toward quantifying the abuse liability of ultraviolet tanning: A behavioral economic approach to tanning addiction
Authors: Reed Derek D. , Kaplan Brent A. , Becirevic Amel , Roma Peter G. , Hursh Steven R.
Published: July 2016

Many adults engage in ultraviolet indoor tanning despite evidence of its association with skin cancer. The constellation of behaviors associated with ultraviolet indoor tanning is analogous to that in other behavioral addictions. Despite a growing literature on ultraviolet indoor tanning as an addiction, there remains no consensus on how to identify ultraviolet indoor tanning addictive tendencies. The purpose of the present study was to translate a behavioral economic task more commonly used in substance abuse to quantify the "abuse liability" of ultraviolet indoor tanning, establish construct validity, and determine convergent validity with the most commonly used diagnostic tools for ultraviolet indoor tanning addiction (i.e., mCAGE and mDSM‐IV‐TR). We conducted a between‐groups study using a novel hypothetical Tanning Purchase Task to quantify intensity and elasticity of ultraviolet indoor tanning demand and permit statistical comparisons with the mCAGE and mDSM‐IV‐TR. Results suggest that behavioral economic demand is related to ultraviolet indoor tanning addiction status and adequately discriminates between potential addicted individuals from nonaddicted individuals. Moreover, we provide evidence that the Tanning Purchase Task renders behavioral economic indicators that are relevant to public health research. The present findings are limited to two ultraviolet indoor tanning addiction tools and a relatively small sample of high‐risk ultraviolet indoor tanning users; however, these pilot data demonstrate the potential for behavioral economic assessment tools as diagnostic and research aids in ultraviolet indoor tanning addiction studies.
Role of thrombospondin‐1 expression in colorectal liver metastasis and its molecular mechanism
Authors: Teraoku Hiroki , Morine Yuji , Ikemoto Tetsuya , Saito Yu , Yamada Shinichiro , Yoshikawa Masato , Takasu Chie , Higashijima Jun , Imura Satoru , Shimada Mitsuo
Published: July 2016

Background

Thrombospondin‐1 (THBS‐1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS‐1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial‐mesenchymal transition (EMT), and expression of other relevant molecules.

Methods

Ninety‐four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS‐1 (THBS‐1 high [n = 35] and THBS‐1 low [n = 59]) and tumor growth, Ki‐67 labeling index (Ki‐67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated.

Results

THBS‐1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS‐1 expression (3‐year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS‐1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21–7.71, P = 0.01). THBS‐1 low expression correlated positively with high Ki‐67 LI (P < 0.05) and inversely with E‐cadherin (P < 0.05) and hypoxia inducible factor‐1α (HIF‐1α) expression (P < 0.05); THBS‐1 expression and MVD were not significantly correlated.

Conclusions

Low THBS‐1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS‐1 may be regulated by the HIF‐1 pathway.
Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T
Authors: Joers James M. , Deelchand Dinesh K. , Kumar Anjali , Moheet Amir , Seaquist Elizabeth , Henry Pierre‐Gilles , Öz Gülin
Published: July 2016

Purpose

To evaluate the feasibility of using a clinical magnetic resonance (MR) system and MR spectroscopy (MRS) to measure glucose concentration changes in the human hypothalamus, a structure central to whole‐body glucose regulation.

Subjects and Methods

A time series of MR spectra (semi‐LASER, TE = 28 msec), localized to the bilateral hypothalamus (∼1.6 ml) were obtained at 3T in six healthy subjects at baseline (euglycemia) and during a ∼65–70‐minute‐long hyperglycemic clamp in 11‐minute blocks with interleaved T1 FLASH images to retrospectively assess head motion, and track changes in cerebrospinal fluid (CSF) partial volume. The LCModel was used to quantify the sum of glucose and taurine concentrations, [Glc+Tau], along with their associated Cramér‐Rao lower bounds (CRLB).

Results

Spectral quality allowed quantification of [Glc+Tau] (sum reported due to high negative correlation between these metabolites) with CRLB <25% in 35/36 timepoints during hyperglycemia. Increased [Glc+Tau] was observed with hyperglycemia in all subjects, but most reliably in those with plasma glucose targets ≥300 mg/dl. For these subjects, [Glc+Tau]baseline (n = 4) was 1.5 (±0.3, SD) mM, and increased to 4.5 (±1.1) mM (n = 16) for timepoints acquired ≥25 minutes after onset of the clamp, with 15/16 timepoints having no overlap of 95% confidence intervals (CIs) between baseline and hyperglycemia. Preliminary analysis revealed a linear (1:5) relationship between hypothalamus–blood glucose concentrations.

Conclusion

It is feasible to measure glucose concentration changes in the human hypothalamus using a standard 3T scanner and a short‐echo semi‐LASER sequence by utilizing retrospective motion tracking, CSF correction, predetermined quality acceptance criteria, and hyperglycemic blood glucose levels ≥300 mg/dl.

Level of Evidence: 2

J. Magn. Reson. Imaging 2017;45:681–691.
Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms
Authors: Burke Nikita N. , Finn David P. , McGuire Brian E. , Roche Michelle
Published: July 2016

A wealth of research over the past 2 decades has expanded our understanding of the impact of early‐life adversity on physiological function and, consequently, health and wellbeing in later life. Early‐life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early‐life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic‐pituitary‐adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early‐life psychological stress and chronic pain, is provided. Greater understanding of the impact of early‐life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. © 2016 Wiley Periodicals, Inc.
Structural changes in the inner ear over time studied in the experimentally deafened guinea pig
Authors: Fransson Anette , Ulfendahl Mats
Published: July 2016

Today a cochlear implant (CI) may significantly restore auditory function, even for people with a profound hearing loss. Because the efficacy of a CI is believed to depend mainly on the remaining population of spiral ganglion neurons (SGNs), it is important to understand the timeline of the degenerative process of the auditory neurons following deafness. Guinea pigs were transtympanically deafened with neomycin, verified by recording auditory brainstem responses (ABRs), and then sacrificed at different time points. Loss of SGNs as well as changes in cell body and nuclear volume were estimated. To study the effect of delayed treatment, a group of animals that had been deaf for 12 weeks was implanted with a stimulus electrode mimicking a CI, after which they received a 4‐week treatment with glial cell‐derived neurotrophic factor (GDNF). The electrical responsiveness of the SGNs was measured by recording electrically evoked ABRs. There was a rapid degeneration during the first 7 weeks, shown as a significant reduction of the SGN population. The degenerative process then slowed, and there was no difference in the amount of remaining neurons between weeks 7 and 18. © 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Aerosol radiative effects under clear skies over Europe and their changes in the period of 2001–2012
Authors: Bartók Blanka
Published: July 2016

In the study, the clear‐sky aerosol radiative effects have been quantified at 52 European sites using empirical and radiative transfer modelling approaches. Furthermore, the trends of the aerosol radiative effects are also determined for the period of 2001–2012. The aerosol radiative effects are simulated using the Mesoscale Atmospheric Global Irradiance Code radiation code with aerosol and water vapour climatology. The annual mean of the surface aerosol radiative effects in clear‐sky situations over Europe is −7.1 ± 2.9 W m−2. The trends of the aerosol radiative effects are derived assigning radiative effects to monthly Moderate Resolution Imaging Spectroradiometer aerosol optical depth time series applying linear fitting. In the indirect approach, the clear‐sky situations are selected from daily surface solar radiation observations from the Word Radiation Data Centre, and the trends of the aerosol radiative effects are delimitated in these clear‐sky radiation time series. The two approaches give good fit, based on the direct approach the annual trend of the aerosol radiative effects on clear‐sky solar surface radiation is −4.41 W m−2 per decade for the period of 2001–2013, while in the case of the indirect approach, this trend is found to be −4.46 W m−2 per decade. The seasonal trends of the aerosol radiative effects vary between −7.57 and −0.17 W m−2 per decade indicating stronger decreases in summertime. The results are presented for four sub‐regions of Europe detecting negative changes in all cases with a stronger decrease in the central, north‐eastern and southern part of the continent. The trends of the aerosol radiative effect have the same magnitude as the trends detected in clear‐sky solar surface radiation, and are an order of magnitude higher than the radiative effects of water vapour (0.20 W m−2 per decade).