bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting
Authors: Linder Lauren M. , Ross Clint A. , Weant Kyle A.
Published: November 2017

Traditional first‐line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting. A literature review was conducted to identify articles utilizing ketamine in the prehospital setting. The review was limited to English‐language articles identified in Embase (1988–June 2017) and the U.S. National Library of Medicine (1970–June 2017). References of all pertinent articles were also reviewed. Ten articles were identified including 418 patients receiving ketamine for agitation. The most commonly utilized route for administration was intramuscular (IM), with five of the seven IM administration studies using a ketamine dose of 5 mg/kg. Ketamine administered in this fashion was efficacious to achieve proper sedation during transport and did not require repeat dosing. Three studies applied a ketamine protocol to outline dosing and the management of ketamine adverse events. The most common adverse events identified were respiratory‐related events and hypersalivation. Ketamine has a role for agitation management in the prehospital setting; however, emergency personnel education and ketamine protocols should be utilized to aid in safe and effective pharmacotherapy and provide guidance on the management of adverse events. Future prospective comparative studies, with protocolized standard ketamine regimens, are needed to further delineate the role of ketamine in agitation management and identify accurate adverse event incidence rates.
Is secretion of IFN‐gamma in response to Mycobacterium tuberculosis antigens in youngest children sufficient to play a role in TB diagnostics?
Authors: Bielecka Teresa , Komorowska‐Piotrowska Anna , Krenke Katarzyna , Feleszko Wojciech , Kulus Marek
Published: November 2017

Objectives

To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN‐ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON‐TB Gold in‐Tube test (QFT‐GIT), (Cellestis Ltd., Australia). Working hypothesis: Is TB‐antigen‐induced IFN‐ɣ response in children ≤5 years sufficient to consider QFT‐GIT a possible tool for TB diagnostics? Study design, patient‐subject selection, and methods: We recruited children 0‐17 years old suspected of TB infection to this cross‐sectional study, in whom QFT–GIT and TST were performed. We analyzed the median IFN‐ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN‐ɣ level in both tubes and age.

Results

A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN‐ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN‐ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = −0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = −0.39, P = 0.01).

Conclusions

The youngest children release sufficient amount of IFN‐ɣ in response to TB antigens thus QFT‐GIT might be a useful tool for TB diagnostics in this age group.
Regional lung function testing in children using electrical impedance tomography
Authors: Vogt Barbara , Löhr Sarah , Zhao Zhanqi , Falkenberg Christian , Ankermann Tobias , Weiler Norbert , Frerichs Inéz
Published: November 2017

Objective

To evaluate regional lung function in lung‐healthy children before and after exercise challenge using electrical impedance tomography (EIT).

Methods

Regional lung function was examined using EIT in 100 lung‐healthy children (three age subgroups: 74‐121, 122‐155, 156‐195 months) at baseline and 10 min after exercise. Global lung function was assessed by spirometry using Z‐Scores of FEV1, FVC, FEV1/FVC, and FEF75. The same lung function measures were determined in 912 EIT image pixels to enable the spatial and temporal ventilation distribution analysis. Coefficients of variation (CV) of these pixel values were calculated and histograms of pixel FEV1/FVC and times required to exhale 50% and 75% of pixel FVC (t50 and t75) generated. Additionally, we compared the findings of the studied population with three cystic fibrosis (CF) children.

Findings

Z‐Scores corresponded to the worldwide reference values in all studied age groups at baseline. Global lung function was not affected by exercise, only the youngest group exhibited higher FVC and lower FEF75, FEV1/FVC attributable to the training effect. The overall degree of ventilation heterogeneity assessed by CV showed no exercise dependency. The histograms of pixel values of FEV1/FVC, t50, and t75 revealed a slight modulating effect of exercise on regional ventilation distribution in all subgroups. EIT identified the distinctly higher ventilation heterogeneity in the CF children.

Conclusion

Global and regional lung functions were not affected by exercise in lung‐healthy children. Exercise did not increase ventilation inhomogeneity. The obtained EIT‐derived regional lung parameters can serve as reference values for future studies in children with lung diseases.
Vertical‐Type Blue Light Emitting Diode by Mixed‐Source Hydride Vapor Phase Epitaxy Method
Authors: Jeon Injun , Bae Sung Geun , Jeon Hunsoo , Kim Kyoung Hwa , Yang Min , Yi Sam Nyung , Ahn Hyung Soo , Yu Young Moon , Sawaki Nobuhiko , Kim Suck‐Whan
Published: November 2017

A vertical‐type blue light‐emitting diode (BLED) was fabricated without a conventional substrate by the mixed‐source hydride vapor phase epitaxy (HVPE) method, wherein the reactor was equipped with a multi‐graphite boat filled with the mixed source for consecutive growth and regulation of the growth rate inside the source zone and a radio‐frequency (RF) heating‐coil to attain high temperatures (T > 900 °C) outside the source zone, which is different from the existing HVPE equipment. The vertical‐type BLED with an active layer of GaN was fabricated by only four production steps: i) photolithography process for manufacturing the mask, ii) epitaxial layer growth process for consecutive growth using the multi‐graphite boat, iii) sorting process to place the bare chips into the holes in a pocket‐type shadow mask for the deposition of the electrodes, and iv) metallization process. The characteristics of the emitted light and the growth thickness measured by a field emission scanning electron microscope (FE‐SEM) and a transmission electron microscope (TEM) revealed that we succeeded in producing the vertical‐type BLED by the mixed‐source HVPE method.
AlGaN/GaN/AlGaN DH‐HEMTs Grown on a Patterned Silicon Substrate
Authors: Comyn Rémi , Chenot Sébastien , Alouani Wissam El , Nemoz Maud , Frayssinet Eric , Damilano Benjamin , Cordier Yvon
Published: November 2017

In the present work, a Si (111) substrate has been patterned with 120‐μm wide square mesas separated by 5‐μm deep grooves. An Al0.29Ga0.71N/GaN HEMT structure was grown by molecular beam epitaxy with a 2‐μm thick Al0.15Ga0.85N buffer on a strain‐mitigating stack previously developed for GaN and low Al‐content AlGaN buffers. Surface inspections confirm the absence of cracks and roughness modification compared to planar growth. Interestingly, contrary to planar growth, X‐ray diffraction shows that plastic strain relaxation was inhibited within the 150‐nm GaN channel grown on top of the Al0.15Ga0.85N buffer. Devices were fabricated in order to assess the electrical properties of the grown films. C–V and TLM measurements reveal the presence of a 2DEG with a density of 7 × 1012 cm−2 and a sheet resistance around 450 Ω □−1. Round geometry transistors were measured up to 200–V drain bias. Compared to devices previously fabricated on planar structures with Al0.05Ga0.95N buffers, an order of magnitude lower off‐state leakage currents were obtained thanks to the larger Al content in the buffer.
Tunable Magnetocaloric Performance of Cluster Microfibers Induced by Magnetization Direction
Authors: Liu Jingshun , Wu Mengjun , Zhang Luhan , Wang Qixiang , Zhang Yun , Yu Tianchi , Shen Hongxian , Li Feng , Peng Huaxin
Published: November 2017

Herein, the work describes a comparative study of the magnetocaloric performance along different magnetization directions of cluster Gd‐based fibers for potential applications. Experimental results indicate that there exists the relatively obvious difference of magnetocaloric effect (MCE) in both longitudinal and transverse magnetization directions. Moreover, the isothermal magnetic entropy changes −ΔSm of 10.62 J kg−1 K−1 and refrigerant capacity (RC) of 756.37 J kg−1 of cluster fibers in transverse direction exhibit a higher value than those in longitudinal direction at relatively high field. This distinction depends on magnetic coupling (magnetic charges induced by electron spin‐orbit polarization) among cluster fibers and magnetic anisotropy (namely magnetic moment rotation) by the action of high magnetic field energy. Therefore, the cluster fibers by changing magnetization direction can provide an effective MCE modulation or to be a candidate for practical magnetic refrigeration applications.
Epsilon‐Negative Active Composites: Loss‐Free and Amplifying Plasmonic Materials
Authors: Kim Kwang‐Hyon
Published: November 2017

The main issue restricting the applications of plasmonics is the intrinsic losses in metals. In order to mitigate the effects of losses, plasmonic systems embedded with gain layers have extensively been investigated over the years. However, the ultimate solution is to use loss‐free or amplifying epsilon‐negative materials. This work reveals that the goal can be achieved by using gain composite materials containing metal nanoparticles as building blocks for plasmonics. By controlling the gain coefficient of the host medium and the filling factor of metal nanoparticles, one can significantly change the magnitude of the negative effective dielectric function while maintaining gain. Their superior performances are evidenced by the evaluations of quality factors for localized and propagating plasmons, and also the detailed studies of spasing behaviors of the composite nanoparticles and hyperbolic responses of their multilayered structures. The findings presented in this work introduce a new paradigm of plasmonics.
All‐sky satellite data assimilation at operational weather forecasting centres
Authors: Geer Alan J. , Lonitz Katrin , Weston Peter , Kazumori Masahiro , Okamoto Kozo , Zhu Yanqiu , Liu Emily Huichun , Collard Andrew , Bell William , Migliorini Stefano , Chambon Philippe , Fourrié Nadia , Kim Min‐Jeong , Köpken‐Watts Christina , Schraff Christoph
Published: November 2017

This article reviews developments towards assimilating cloud‐ and precipitation‐ affected satellite radiances at operational forecasting centres. Satellite data assimilation is moving beyond the “clear‐sky” approach that discards any observations affected by cloud. Some centres already assimilate cloud‐ and precipitation‐affected radiances operationally and the most popular approach is known as “all‐sky,” which assimilates all observations directly as radiances, whether they are clear, cloudy or precipitating, using models (for both radiative transfer and forecasting) that are capable of simulating cloud and precipitation with sufficient accuracy. Other frameworks are being tried, including the assimilation of humidity retrieved from cloudy observations using Bayesian techniques. Although the all‐sky technique is now proven for assimilation of microwave radiances, it has yet to be demonstrated operationally for infrared radiances, though several centres are getting close. Assimilating frequently available all‐sky infrared observations from geostationary satellites could give particular benefit for short‐range forecasting. More generally, assimilating cloud‐ and precipitation‐affected satellite observations improves forecasts in the medium range globally and can also improve the analysis and shorter‐range forecasting of otherwise poorly observed weather phenomena as diverse as tropical cyclones and wintertime low cloud.
Reactivity descriptors for DNA bases and the methylation of cytosine
Authors: Jerbi Jihène , Springborg Michael
Published: November 2017

This work is devoted to the reactivity of DNA bases and base pairs. Various global molecular descriptors for reactivity were studied in addition to local descriptors for Cytosine and Cytosine‐Guanine base pairs using three different ways of analysing the charge distribution. The process of methylation was selected since it is very important during the cell formation at the embryonic state and since much is already known about this system making an assessment of the quality of the theoretical approaches possible. The results reveal that Cytosine is the least reactive molecule among the bases although it can be attacked by the DNMT enzyme while paired with Guanine. Amain finding of the present work is, however, that by analysing the Fukui function and a dual descriptor we can rationalise that carbon at position 5 of Cytosine is the most favorable site for the methyl attack.
Effect of deprotonation on the magnetic exchange coupling constant of fluorene‐based verdazyl diradical: A computational study
Authors: Shil Suranjan
Published: November 2017

The magnetic behavior of the fluorene bridged verdazyl diradicals has been studied theoretically in their neutral and deprotonated states. The deprotonation of C9‐H site of the fluorene ring opens a new coupling pathway, which changes the nature of magnetic coupling. The transmission spectra analysis reveals that the transmission through fluorine has also increased due to the opening of a new coupling path after deprotonation.
A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease
Authors: Osibogun Olatokunbo , Ogunmoroti Oluseye , Michos Erin D. , Spatz Erica S. , Olubajo Babatunde , Nasir Khurram , Maziak Wasim
Published: November 2017

The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima‐media thickness (CIMT), endothelial markers, C‐reactive protein (CRP), homocysteine, and lipids. Among 332 articles screened, 28 were included (39,498 participants). Study designs varied: 18 cross‐sectional, 9 cohort, and 1 clinical trial. Compared with healthy controls and people with HIV or HCV monoinfection, individuals with HIV/HCV coinfection had statistically significant lower levels of lipids and CRP and higher levels of endothelial markers (sICAM‐1 and sVCAM‐1), CIMT, homocysteine, and IL‐6. One study found the odds of carotid plaque in coinfected individuals was 1.64 (0.91–2.94) compared with healthy controls, and another study showed the prevalence of vascular plaques (carotid and femoral) in coinfected individuals was higher compared with HIV monoinfected individuals (44% vs 14%, P = 0.04). Biomarkers of CVD have different patterns of association with HIV/HCV coinfection compared with monoinfection and healthy controls. Prospective studies are needed to confirm the predictive value of these biomarkers for clinical CVD risk among coinfected individuals.
Mild Thio‐Diversification of Bioactive Natural Products. Withaferin A: A Case study.
Authors: Casero C. N. , Novillo J. N. Garay , García M. E. , Oberti J. C. , Nicotra V. E. , Peñéñory A. B. , Bisogno F. R.
Published: November 2017

A sustainable strategy was developed to create chemical diversity from bioactive scaffolds. The methodology comprises a set of simple reactions between the parent compound (i. e. withaferin A), and small sulfur nucleophiles in hydroalcoholic media, at room temperature and in open‐air atmosphere. Novel steroidal sulfur natural product‐analogs were obtained, featuring ring opening, ring formation, new stereocenters and modulation of parameters useful in medicinal chemistry.
Room Temperature Reduction of Nitroaromatics Using Pd Nanoparticles Stabilized on Nano‐CeO2
Authors: Saikia Himadri , Borah Biraj Jyoti , Bharali Pankaj
Published: November 2017

Palladium nanoparticles stabilized on mesoporous cerium oxide nanoparticles catalyze the reduction of substituted nitroaromatics in presence of sodium borohydride as reductant. A modified two‐step methodology was developed for the synthesis of Pd/CeO2 nanoparticles. First the support CeO2 was synthesized by conventional precipitation method using ammonium oxalate as precipitant and Pd/CeO2 nanoparticles were prepared by hydrothermal treatment. The nanoparticles exhibit excellent catalytic activity and chemoselectivity for the reduction of nitroaromatics towards corresponding amine derivatives at room temperature. A kinetic study suggests that the reaction follows pseudo‐first order rate equation. Thus, synthesized catalyst represents significant role for the reduction of nitroaromatic compounds to value added amino compounds.
Eco‐Friendly Alkali‐Free Arginine‐Assisted Hydrothermal Synthesis of Different Layered Double Hydroxides and Their Chromate Adsorption/Reduction Efficiency
Authors: Koilraj Paulmanickam , Sasaki Keiko
Published: November 2017

A new one‐pot synthesis of highly crystalline MgAl‐, CoAl‐ and ZnAl‐layered double hydroxides (LDHs) containing NO3− as interlayer anion along with the surface functionalization of L‐arginine was demonstrated by the ecofriendly alkali‐free arginine‐assisted hydrothermal method to examine the adsorptive reduction of chromate (CrO42−) from aqueous solutions. The amino acid mediated water hydrolysis resulted abundant OH− in the medium, which served as precipitant, and the NO3− from metal precursor acts as an interlayer anion along with surface functionalization of amino acid. Adsorption studies revealed that the removal of CrO42− by anion exchange was the greatest in MgAl‐LDH with 1.619 mmol‐Cr/g of LDH. The mechanism of CrO42− removal was due to the ion‐exchange of NO3− from the interlayer as well as the counter anions present on the functionalized arginine cation. The adsorbed CrO42− was partially reduced to nontoxic Cr3+ on the surface of LDH due to the presence of amino acid functionalization. The present technique provides several advantages from the aspect of sustainable chemistry: (i) avoiding hazardous alkali for the preparation of LDH, (ii) removal of CrO42− by ion‐exchange and (iii) partial detoxification of CrO42− by reduction to Cr3+ on the surface of the LDH.
Ni‐Nanocluster Modified Black TiO2 with Dual Active Sites for Selective Photocatalytic CO2 Reduction
Authors: Billo Tadesse , Fu Fang‐Yu , Raghunath Putikam , Shown Indrajit , Chen Wei‐Fu , Lien Hsiang‐Ting , Shen Tzu‐Hsien , Lee Jyh‐Fu , Chan Ting‐Shan , Huang Kuo‐You , Wu Chih‐I , Lin M. C. , Hwang Jih‐Shang , Lee Chih‐Hao , Chen Li‐Chyong , Chen Kuei‐Hsien
Published: November 2017

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni‐nanocluster loaded black TiO2 (Ni/TiO2[Vo]) with built‐in dual active sites for selective photocatalytic CO2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO2 (P‐25). An insight into the mechanisms of interfacial charge transfer and product formation is explored.
Uranium Oxide Nanocrystals by Microwave‐Assisted Thermal Decomposition: Electronic and Structural Properties
Authors: Leduc Jennifer , Pacold Joseph I. , Shuh David K. , Dong Chung‐Li , Mathur Sanjay
Published: November 2017

Uranium oxides have attracted much attention not only in the context of nuclear energy generation but also for their application as pristine catalysts or as supports for other (transition metal) oxides and (precious) metals. Their propensity to adopt high coordination numbers and manifest multiple oxidation states (from +II to +VI) makes them attractive candidates for catalyzed transformation reactions. Herein, we report a new synthesis route to phase‐pure, crystalline UO2 nanoparticles via microwave‐assisted decomposition of a molecular uranium(IV) precursor. The electronic structure and optical absorption properties of these nanocrystals were investigated using spectroscopic methods to evaluate their suitability for photo(electro)catalytic applications.
Tungsten Disilicide (WSi2): Synthesis, Characterization, and Prediction of New Crystal Structures
Authors: Luković Jelena , Zagorac Dejan , Schön J. Christian , Zagorac Jelena , Jordanov Dragana , Volkov‐Husović Tatjana , Matović Branko
Published: November 2017

Transition metal silicides have attracted great attention due to their potential applications in microelectronics, ceramics, and the aerospace industry. In this study, experimental and theoretical investigations of tungsten based silicides were performed. Tungsten disilicide (WSi2) was synthesized by simple thermal treatment at 1350 °C for 4 h in an argon atmosphere. These optimal synthesis conditions were obtained by variation of temperatures and times of heating, and the structure of the final synthesized compound was determined by XRPD analysis. In addition, new modifications for WSi2 were proposed and investigated using first‐principles calculations within density‐functional theory (DFT). Both LDA and PBE calculations show excellent agreement with experimental observations and previous calculations for the existing modifications, where available.
The quantum Fokker-Planck equation of stochastic inflation
Authors: Collins Hael , Holman Richard , Vardanyan Tereza
Published: November 2017

Abstract

We derive the stochastic description of a massless, interacting scalar field in de Sitter space directly from the quantum theory. This is done by showing that the density matrix for the effective theory of the long wavelength fluctuations of the field obeys a quantum version of the Fokker-Planck equation. This equation has a simple connection with the standard Fokker-Planck equation of the classical stochastic theory, which can be generalised to any order in perturbation theory. We illustrate this formalism in detail for the theory of a massless scalar field with a quartic interaction.
Constraining neutrino masses, the cosmological constant and BSM physics from the weak gravity conjecture
Authors: Ibáñez Luis E. , Martín-Lozano Víctor , Valenzuela Irene
Published: November 2017

Abstract

It is known that there are AdS vacua obtained from compactifying the SM to 2 or 3 dimensions. The existence of such vacua depends on the value of neutrino masses through the Casimir effect. Using the Weak Gravity Conjecture, it has been recently argued by Ooguri and Vafa that such vacua are incompatible with the SM embedding into a consistent theory of quantum gravity. We study the limits obtained for both the cosmological constant Λ4 and neutrino masses from the absence of such dangerous 3D and 2D SM AdS vacua. One interesting implication is that Λ4 is bounded to be larger than a scale of order m

ν

4
, as observed experimentally. Interestingly, this is the first argument implying a non-vanishing Λ4 only on the basis of particle physics, with no cosmological input. Conversely, the observed Λ4 implies strong constraints on neutrino masses in the SM and also for some BSM extensions including extra Weyl or Dirac spinors, gravitinos and axions. The upper bounds obtained for neutrino masses imply (for fixed neutrino Yukawa and Λ4) the existence of upper bounds on the EW scale. In the case of massive Majorana neutrinos with a see-saw mechanism associated to a large scale M ≃ 1010 − 14 GeV and Y

ν1 ≃ 10−3, one obtains that the EW scale cannot exceed M

EW
≲ 102 − 104 GeV. From this point of view, the delicate fine-tuning required to get a small EW scale would be a mirage, since parameters yielding higher EW scales would be in the swampland and would not count as possible consistent theories. This would bring a new perspective into the issue of the EW hierarchy.
The transverse momentum distribution of hadrons within jets
Authors: Kang Zhong-Bo , Liu Xiaohui , Ringer Felix , Xing Hongxi
Published: November 2017

Abstract

We study the transverse momentum distribution of hadrons within jets, where the transverse momentum is defined with respect to the standard jet axis. We consider the case where the jet substructure measurement is performed for an inclusive jet sample pp → jet + X. We demonstrate that this observable provides new opportunities to study transverse momentum dependent fragmentation functions (TMDFFs) which are currently poorly constrained from data, especially for gluons. The factorization of the cross section is obtained within Soft Collinear Effective Theory (SCET), and we show that the relevant TMDFFs are the same as for the more traditional processes semi-inclusive deep inelastic scattering (SIDIS) and electron-positron annihilation. Different than in SIDIS, the observable for the in-jet fragmentation does not depend on TMD parton distribution functions which allows for a cleaner and more direct probe of TMDFFs. We present numerical results and compare to available data from the LHC.
Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra
Authors: Václavík Jan , Coene Karlien L. M. , Vrobel Ivo , Najdekr Lukáš , Friedecký David , Karlíková Radana , Mádrová Lucie , Petsalo Aleksanteri , Engelke Udo F. H. , van Wegberg Annemiek , Kluijtmans Leo A. J. , Adam Tomáš , Wevers Ron A.
Published: November 2017

Specific diagnostic markers are the key to effective diagnosis and treatment of inborn errors of metabolism (IEM). Untargeted metabolomics allows for the identification of potential novel diagnostic biomarkers. Current separation techniques coupled to high‐resolution mass spectrometry provide a powerful tool for structural elucidation of unknown compounds in complex biological matrices. This is a proof‐of‐concept study testing this methodology to determine the molecular structure of as yet uncharacterized m/z signals that were significantly increased in plasma samples from patients with phenylketonuria and 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency. A hybrid linear ion trap‐orbitrap high resolution mass spectrometer, capable of multistage fragmentation, was used to acquire accurate masses and product ion spectra of the uncharacterized m/z signals. In order to determine the molecular structures, spectral databases were searched and fragmentation prediction software was used. This approach enabled structural elucidation of novel compounds potentially useful as biomarkers in diagnostics and follow‐up of IEM patients. Two new conjugates, glutamyl‐glutamyl‐phenylalanine and phenylalanine‐hexose, were identified in plasma of phenylketonuria patients. These novel markers showed high inter‐patient variation and did not correlate to phenylalanine levels, illustrating their potential added value for follow‐up. As novel biomarkers for 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency, three positional isomers of 3‐methylglutaconyl carnitine could be detected in patient plasma. Our results highlight the applicability of current accurate mass multistage fragmentation techniques for structural elucidation of unknown metabolites in human biofluids, offering an unprecedented opportunity to gain further biochemical insights in known inborn errors of metabolism by enabling high confidence identification of novel biomarkers.
Broad scale variation in seagrass benthic macrofaunal assemblages along the coast of Japan
Authors: Leopardas Venus , Hori Masakazu , Mukai Hiroshi , Tanaka Yoshiyuki , Yokoi Ken‐ichi , Aoki Misuzu , Sato Naoto , Whanpetch Napakhwan , Nakaoka Masahiro
Published: November 2017

Broad scale studies in seagrass benthic macrofauna are important for future regional marine conservation. We examined spatial variation in the community structure of seagrass‐associated benthic macroinvertebrates collected by sediment coring in 2010 at six seagrass sites of Japan covering the latitudinal range of 24°–43°N. Total species richness and ES(50) at site level did not show clear site variations and relationship with latitude. At core level, site variations of mean species richness, ES(50), Simpson diversity and abundance showed inconsistent pattern, but with more cases of statistically significant association with latitude. Variations were generally influenced by the seagrass species, often among subtropical species, among temperate Zostera species, and between Zostera and subtropical species. Finally, the community composition differed significantly across all sites and community similarity decreased rapidly with geographic distance, with only 5% similarity retained at the distance of 400 km. The dissimilarity among sites was higher with the similar distance compared to other types of coastal communities such as rocky intertidal assemblages, which is associated with minor occurrence of species with broad distributional range.
Plant functional traits and groups in a Californian serpentine chaparral
Authors: Hidalgo‐Triana Noelia , Pérez Latorre Andrés Vicente , Thorne James Hansen
Published: November 2017

We studied a type of Californian ultramafic chaparral to determine functional groups which can help reduce the complexity of ecosystem management. The study was realized in McLaughlin Reserve, State of California, USA. We analysed the species of a serpentine plant association previously phytosociologically described in the area: Ceanotho albiflori‐Quercetum duratae for their functional traits and functional groups. Traits per species were measured building a trait database. We used Principal Component Analysis to identify the combination of functional traits with major weight and a neighbor‐joining clustering to define functional groups for this vegetation association. Our results indicated that the studied association is dominated by phanerophytes, with low degree of spinescence. Leaves were mainly malacophyllous with high degree of tomentosity, reduced size and a partial shedding of leaves was observed during summer. We considered six functional groups as the optimum number of clusters in a total of 18 species. The two first functional groups were composed of chamaephytes with brachyblasts and dolichoblasts with differences in the degree of tomentosity. The rest of the functional groups were composed of phanerophytes where the differences between them were based on traits in relation to the branches, leaf size and the horizontal development of the root system. The functional groups obtained show that this serpentine chaparral is composed of species with a wide range of functional traits. The study of other Mediterranean serpentine ecosystems in California and elsewhere could contribute to create new perspectives of functional ecology and help in the management of these valuable ecosystems.
Well-posedness of the linearized Prandtl equation around a non-monotonic shear flow
Authors: Chen Dongxiang , Wang Yuxi , Zhang Zhifei
Published: November 2017

In this paper, we prove the well-posedness of the linearized Prandtl equation around a non-monotonic shear flow in Gevrey class

2−\theta

for any

\theta > 0

. This result is almost optimal by the ill-posedness result proved by Gérard-Varet and Dormy, who construct a class of solution with the growth like

e^{\sqrt{k}t}

for the linearized Prandtl equation around a non-monotonic shear flow.
EDITORIAL
Authors: Colmar Susan
Published: November 2017

I am pleased to introduce a paper for our Applied Practices’ section of the journal, which is entitled Working Memory Interventions with Children: Classrooms or Computers? As one of the authors of this paper, with my colleague Kit Double, I can confirm that its scope is to examine what types of interventions for working memory in children currently exist, their relative efficacy in impacting working memory itself, as well as academic achievement, self concept and classroom engagement. Importantly, we explore the relative paucity of effective interventions, despite current rhetoric about the importance of working memory as a key part of executive functions. The role of attention factors, which are critical to working memory being used appropriately, is also examined. I recommend this paper to you all to challenge your preconceptions and to realistically evaluate what you can and should consider when advising about working memory as part of your practice.
Ricasolia amplissima(Lobariaceae): one species, three genotypes and a new taxon from south-eastern Alaska
Authors: CORNEJO Carolina , DERR Chiska , DILLMAN Karen
Published: November 2017

The genetic diversity within the foliose form ofRicasolia amplissimafrom Europe and North America was studied using molecular phylogenetic analysis of the nuclear ITS andRPB2, and mitochondrial SSU. Boundaries between closely related species were also examined using morphological and chemical patterns. Four species of the recently reinstated lichen genusRicasoliaDe Not. were phylogenetically verified which necessitated a new combination,Ricasolia japonica(Asah.) Cornejo. Analyses suggest that the generic type taxonR. amplissima(Scop.) De Not. belongs to a species complex that shows two evolutionary centres, one in Europe, North Africa, Asia Minor and the Macaronesian Islands, the other from north-western North America on exposed shores of mainly forested marine islands in south-eastern Alaska, where it shows strong habitat specificity. The Alaskan lineage is very similar to the European lineage but it differs by the lack of scrobiculin and other chemical substances. It is described here asR. amplissimasubsp.sheiyiDerr & Dillman.
Selective deletion of the soluble Colony-Stimulating Factor 1 isoform in vivo prevents estrogen-deficiency bone loss in mice
Authors: Yao Gang-Qing , Troiano Nancy , Simpson Christine A , Insogna Karl L
Published: November 2017

Neutralizing CSF1in vivocompletely prevents ovariectomy (OVX)-induced bone loss in mice. There are two isoforms of CSF1, soluble (sCSF1), and membrane-bound (mCSF1), but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout (K/O) and wild type (Wt) female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected (sCSF1 K/O). Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density (BMD) between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of +0.1%, −2.4%, and +2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.
Two approaches reveal a new paradigm of ‘switchable or genetics-influenced allele-specific DNA methylation’ with potential in human disease
Authors: Martos Suzanne N , Li Teng , Ramos Ramon Bossardi , Lou Dan , Dai Hongzheng , Xu Jin-Chong , Gao Ganglong , Gao Yang , Wang Qinglu , An Cheng , Zhang Xueli , Jia Yankai , Dawson Valina L , Dawson Ted M , Ji Hongkai , Wang Zhibin
Published: November 2017

Imprinted genes are vulnerable to environmental influences during early embryonic development, thereby contributing to the onset of disease in adulthood. Monoallelic methylation at several germline imprints has been reported as DNMT1-dependent. However, which of these two epigenetic attributes, DNMT1-dependence or allelic methylation, renders imprinted genes susceptible to environmental stressors has not been determined. Herein, we developed a new approach, referred to as NORED, to identify 2468 DNMT1-dependent DNA methylation patterns in the mouse genome. We further developed an algorithm based on a genetic variation-independent approach (referred to as MethylMosaic) to detect 2487 regions with bimodal methylation patterns. Two approaches identified 207 regions, including known imprinted germline allele-specific methylation patterns (ASMs), that were both NORED and MethylMosaic regions. Examination of methylation in four independent mouse embryonic stem cell lines shows that two regions identified by both NORED and MethylMosaic (Hcn2 and Park7) did not display parent-of-origin-dependent allelic methylation. In these four F1 hybrid cell lines, genetic variation in Cast allele at Hcn2 locus introduces a transcription factor binding site for MTF-1 that may predispose Cast allelic hypomethylation in a reciprocal cross with either C57 or 129 strains. In contrast, each allele of Hcn2 ASM in J1 inbred cell line and Park7 ASM in four F1 hybrid cell lines seems to exhibit similar propensity to be either hypo- or hypermethylated, suggesting a ‘random, switchable’ ASM. Together with published results, our data on ASMs prompted us to propose a hypothesis of regional ‘autosomal chromosome inactivation (ACI)’ that may control a subset of autosomal genes. Therefore, our results open a new avenue to understand monoallelic methylation and provide a rich resource of candidate genes to examine in environmental and nutritional exposure models.
Metabolic shift at the class level sheds light on adaptation of methanogens to oxidative environments
Authors: Lyu Zhe , Lu Yahai
Published: November 2017

Methanogens have long been considered strictly anaerobic and oxygen-sensitive microorganisms, but their ability to survive oxygen stress has also been documented. Indeed, methanogens have been found in oxidative environments, and antioxidant genes have been detected in their genomes. How methanogens adapt to oxidative environments, however, remain poorly understood. Here, we systematically predicted and annotated antioxidant features from representative genomes across six well-established methanogen orders. Based on functional gene content involved in production of reactive oxygen species, Hierarchical Clustering analyses grouped methanogens into two distinct clusters, corresponding to the Class I and II methanogens, respectively. Comparative genomics suggested a systematic shift in metabolisms across the two classes, resulting in an enrichment of antioxidant features in the Class II. Moreover, meta-analysis of 16 S rRNA gene sequences obtained from EnvDB indicated that members of Class II were more frequently recovered from microaerophilic and even oxic environments than the Class I members. Phylogenomic analysis suggested that the Class I and II methanogens might have evolved before and around the Great Oxygenation Event, respectively. The enrichment of antioxidant features in the Class II methanogens may have played a key role in the adaption of this group to oxidative environments today and historically.
Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling
Authors: Pal Bhupinder , Chen Yunshun , Vaillant François , Jamieson Paul , Gordon Lavinia , Rios Anne C. , Wilcox Stephen , Fu Naiyang , Liu Kevin He , Jackling Felicity C. , Davis Melissa J. , Lindeman Geoffrey J. , Smyth Gordon K. , Visvader Jane E.
Published: November 2017

The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells.
Structural and spatial chromatin features at developmental gene loci in human pluripotent stem cells
Authors: Ikeda Hiroki , Sone Masamitsu , Yamanaka Shinya , Yamamoto Takuya
Published: November 2017

Higher-order chromatin organization controls transcriptional programs that govern cell properties and functions. In order for pluripotent stem cells (PSCs) to appropriately respond to differentiation signals, developmental gene loci should be structurally and spatially regulated to be readily available for immediate transcription, even though these genes are hardly expressed in PSCs. Here, we show that both chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic cells and hPSCs, and that changes in the chromatin interactions are closely related to the nuclear repositioning. Moreover, we also demonstrate that developmental gene loci, which have bivalent histone modifications, tend to colocalize in PSCs. Furthermore, this colocalization requires PRC1, PRC2, and TrxG complexes, which are essential regulatory factors for the maintenance of transcriptionally poised developmental genes. Our results indicate that higher-order chromatin regulation may be an integral part of the differentiation capacity that defines pluripotency.
Host-genotype dependent gut microbiota drives zooplankton tolerance to toxic cyanobacteria
Authors: Macke Emilie , Callens Martijn , De Meester Luc , Decaestecker Ellen
Published: November 2017

The gut microbiota impacts many aspects of its host’s biology, and is increasingly considered as a key factor mediating performance of host individuals in continuously changing environments. Here we use gut microbiota transplants to show that both host genotype and gut microbiota mediate tolerance to toxic cyanobacteria in the freshwater crustacean Daphnia magna. Interclonal variation in tolerance to cyanobacteria disappears when Daphnia are made germ-free and inoculated with an identical microbial inoculum. Instead, variation in tolerance among recipient Daphnia mirrors that of the microbiota donors. Metagenetic analyses point to host genotype and external microbial source as important determinants of gut microbiota assembly, and reveal strong differences in gut microbiota composition between tolerant and susceptible genotypes. Together, these results show that both environmentally and host genotype-induced variations in gut microbiota structure mediate Daphnia tolerance to toxic cyanobacteria, pointing to the gut microbiota as a driver of adaptation and acclimatization to cyanobacterial harmful algal blooms in zooplankton.
Mapping the sugar dependency for rational generation of a DNA-RNA hybrid-guided Cas9 endonuclease
Authors: Rueda Fernando Orden , Bista Michal , Newton Matthew D. , Goeppert Anne U. , Cuomo M. Emanuela , Gordon Euan , Kröner Felix , Read Jon A. , Wrigley Jonathan D. , Rueda David , Taylor Benjamin J. M.
Published: November 2017

The CRISPR–Cas9 RNA-guided endonuclease system allows precise and efficient modification of complex genomes and is continuously developed to enhance specificity, alter targeting and add new functional moieties. However, one area yet to be explored is the base chemistry of the associated RNA molecules. Here we show the design and optimisation of hybrid DNA–RNA CRISPR and tracr molecules based on structure-guided approaches. Through careful mapping of the ribose requirements of Cas9, we develop hybrid versions possessing minimal RNA residues, which are sufficient to direct specific nuclease activity in vitro and in vivo with reduced off-target activity. We identify critical regions within these molecules that require ribose nucleotides and show a direct correlation between binding affinity/stability and cellular activity. This is the first demonstration of a non-RNA-guided Cas9 endonuclease and first step towards eliminating the ribose dependency of Cas9 to develop a XNA-programmable endonuclease.
Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling
Authors: Sassi Yassine , Avramopoulos Petros , Ramanujam Deepak , Grüter Laurenz , Werfel Stanislas , Giosele Simon , Brunner Andreas-David , Esfandyari Dena , Papadopoulou Aikaterini S. , De Strooper Bart , Hübner Norbert , Kumarswamy Regalla , Thum Thomas , Yin Xiaoke , Mayr Manuel , Laggerbauer Bernhard , Engelhardt Stefan
Published: November 2017

Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function. Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types. Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors. Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.