bluuebunny/crossref_metadata_2025 huggingface dataset:
PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium
Authors: Pérez-Lara Ángel , Thapa Anusa , Nyenhuis Sarah B , Nyenhuis David A , Halder Partho , Tietzel Michael , Tittmann Kai , Cafiso David S , Jahn Reinhard
Published: October 2016

The Ca2+-sensor synaptotagmin-1 that triggers neuronal exocytosis binds to negatively charged membrane lipids (mainly phosphatidylserine (PtdSer) and phosphoinositides (PtdIns)) but the molecular details of this process are not fully understood. Using quantitative thermodynamic, kinetic and structural methods, we show that synaptotagmin-1 (from Rattus norvegicus and expressed in Escherichia coli) binds to PtdIns(4,5)P2 via a polybasic lysine patch in the C2B domain, which may promote the priming or docking of synaptic vesicles. Ca2+ neutralizes the negative charges of the Ca2+-binding sites, resulting in the penetration of synaptotagmin-1 into the membrane, via binding of PtdSer, and an increase in the affinity of the polybasic lysine patch to phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2). These Ca2+-induced events decrease the dissociation rate of synaptotagmin-1 membrane binding while the association rate remains unchanged. We conclude that both membrane penetration and the increased residence time of synaptotagmin-1 at the plasma membrane are crucial for triggering exocytotic membrane fusion.
bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring
Authors: Trovisco Vítor , Belaya Katsiaryna , Nashchekin Dmitry , Irion Uwe , Sirinakis George , Butler Richard , Lee Jack J , Gavis Elizabeth R , St Johnston Daniel
Published: October 2016

bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Furthermore, bicoid mRNA localises normally in shot2A2, which abolishes the polarised microtubule organisation. FRAP and photo-conversion experiments demonstrate that the RNA is stably anchored at the anterior, independently of microtubules. Thus, bicoid mRNA is localised by random active transport and anterior anchoring. Super-resolution imaging reveals that bicoid mRNA forms 110–120 nm particles with variable RNA content, but constant size. These particles appear to be well-defined structures that package the RNA for transport and anchoring.
Supercontinuum generation in a step-index chalcogenide fiber with AsSe2 core and As2S5 cladding
Authors: Gao Weiqing , Xu Qiang , Li Xue , Zhang Wei , Hu Jigang , Li Yuan , Chen Xiangdong , Yuan Zijun , Liao Meisong , Li Xia , Bi Wanjun , Cheng Tonglei , Suzuki Takenobu , Ohishi Yasutake
Published: October 2016

We demonstrate the supercontinuum (SC) generation in a chalcogenide step-index fiber with AsSe2 core and As2S5 cladding. The characteristics of fiber are analyzed using the full-vectorial mode solver technique. The fiber has two zero-dispersion wavelengths at 2898 and 5140 nm. The evolving of SC spectra with fiber length and pump wavelength is investigated experimentally. The maximum SC range covering one octave from 1550 to 3300 nm is obtained when the 20 cm long fiber is pumped by 2000 nm pulses in normal dispersion region. The fiber can push forward the nonlinear application based on the stimulated Raman effect, stimulated Brillouin effect, four-wave mixing, supercontinuum generation, and so on in the mid-infrared waveband. The SCs are simulated by the nonlinear Schrödinger equation. The simulated results agree well with the experiments.
Synthesis and electrochemical property of few-layer molybdenum disulfide nanosheets
Authors: Fu Yanjue , Wang Chunrui , Wang Linlin , Peng Xia , Wu Binhe , Sun Xingqu , Chen Xiaoshuang
Published: October 2016

Large-scale few-layer MoS2 nanosheets have been fabricated via a simple hydrothermal route using molybdenum powder as precursors. The as-prepared MoS2 samples were characterized by X-ray powder diffraction (XRD) analysis, transmission electron microscopy (TEM), and Raman and photoluminescence (PL) spectral analyses at room temperature. The results confirm that the as-prepared MoS2 displays a sheet-like morphology with a thickness of few (bi- to tri-) layers. Electrochemical measurements showed that the as-prepared few-layer MoS2 exhibited the highest reversible capacity of 1127 mAh g−1 and a stable reversible capacity of 1057 mAh g−1 after 30 cycles.
Teaching Children Foreign-Language Grammar: Are Authentic Materials Appropriate?
Authors: Malova Olga
Published: October 2016

The paper discusses authentic materials as a resource for teaching grammar to young learners. Difficulties in foreign-language grammar learning for Russian pupils are presented, and typical challenges are described. The paper provides a pre-/post-intervention study of the development of children’s grammar skills. The research question is, “How does one use authentic materials for teaching grammar in an English as a foreign language (EFL) classroom?” A qualitative method is used to assess the learning outcomes of using authentic materials in teaching grammar to eight–nine-year-old pupils (the second year of studying English).
In silico study on anti-Chikungunya virus activity of hesperetin
Authors: Oo Adrian , Hassandarvish Pouya , Chin Sek Peng , Lee Vannajan Sanghiran , Abu Bakar Sazaly , Zandi Keivan
Published: October 2016

Background

The re-emerging,Aedes spp.transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients’ lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication. Here, we present a study using the computational approach to identify possible target proteins for future mechanistic studies of hesperetin.

Methods

3D structures of CHIKV nsP2 (3TRK) and nsP3 (3GPG) were retrieved from Protein Data Bank (PDB), whereas nsP1, nsP4 and cellular factor SPK2 were modeled using Iterative Threading Assembly Refinement (I-TASSER) server based on respective amino acids sequence. We performed molecular docking on hesperetin against all four CHIKV non-structural proteins and SPK2. Proteins preparation and subsequent molecular docking were performed using Discovery Studio 2.5 and AutoDock Vina 1.5.6. The Lipinski’s values of the ligand were computed and compared with the available data from PubChem. Two non-structural proteins with crystal structures 3GPG and 3TRK in complexed with hesperetin, demonstrated favorable free energy of binding from the docking study, were further explored using molecular dynamics (MD) simulations.

Results

We observed that hesperetin interacts with different types of proteins involving hydrogen bonds, pi-pi effects, pi-cation bonding and pi-sigma interactions with varying binding energies. Among all five tested proteins, our compound has the highest binding affinity with 3GPG at −8.5 kcal/mol. The ligand used in this study also matches the Lipinski’s rule of five in addition to exhibiting closely similar properties with that of in PubChem. The docking simulation was performed to obtain a first guess of the binding structure of hesperetin complex and subsequently analysed by MD simulations to assess the reliability of the docking results. Root mean square deviation (RMSD) of the simulated systems from MD simulations indicated that the hesperetin complex remains stable within the simulation timescale.

Discussion

The ligand’s tendencies of binding to the important proteins for CHIKV replication were consistent with our previous in vitro screening which showed its efficacy in blocking the virus intracellular replication. NsP3 serves as the highest potential target protein for the compound’s inhibitory effect, while it is interesting to highlight the possibility of interrupting CHIKV replication via interaction with host cellular factor. By complying the Lipinski’s rule of five, hesperetin exhibits drug-like properties which projects its potential as a therapeutic option for CHIKV infection.
Work Management Style of the College Deans of SUCs in Region 8, Philippines
Authors: Entoma Rolando C.
Published: October 2016

One success indicator of any educational institution depends on the type of management and its capabilities to drive the preplanned goals within the framework of time set forth. The study utilized the descriptive-correlational research design which aimed to determine the work management styles of the college deans of State Universities and Colleges (SUCs) in Region 8, Philippines. Using validated questionnaires, data were statistically treated using weighted mean, percentage and chi-square test of independence. Findings showed that female college deans who are doctorate degree holders, with higher number of years of experience and training attended were the perfectionist in managing their works. It also showed that the college deans' profile has no significant relationship with their work management style. The college deans with the higher number of programs offered were cliff hangers. If given the opportunity to experience more and attend training on leadership and management, perceived control of time, and stress responses, the college deans can play better in their role, functions, and responsibilities. The study contributes to the field of educational administration to create useful solutions in terms of leadership and management styles of college deans for them to be aware and become more productive and efficient leaders.
Investigating the relative permeability behavior of microporosity‐rich carbonates and tight sandstones with multiscale pore network models
Authors: Bultreys Tom , Stappen Jeroen Van , Kock Tim De , Boever Wesley De , Boone Marijn A. , Hoorebeke Luc Van , Cnudde Veerle
Published: October 2016

The relative permeability behavior of rocks with wide ranges of pore sizes is in many cases still poorly understood and is difficult to model at the pore scale. In this work, we investigate the capillary pressure and relative permeability behavior of three outcrop carbonates and two tight reservoir sandstones with wide, multimodal pore size distributions. To examine how the drainage and imbibition properties of these complex rock types are influenced by the connectivity of macropores to each other and to zones with unresolved small‐scale porosity, we apply a previously presented microcomputed‐tomography‐based multiscale pore network model to these samples. The sensitivity to the properties of the small‐scale porosity is studied by performing simulations with different artificial sphere‐packing‐based networks as a proxy for these pores. Finally, the mixed‐wet water‐flooding behavior of the samples is investigated, assuming different wettability distributions for the microporosity and macroporosity. While this work is not an attempt to perform predictive modeling, it seeks to qualitatively explain the behavior of the investigated samples and illustrates some of the most recent developments in multiscale pore network modeling.
Diacetyl (Butandion) [Air Monitoring Methods in German language, 2016a]
Authors: Schuh C. , Kirchner M. , Hebisch R. , Hartwig A. ,   MAK Commission
Published: October 2016

Diacetyl (Butanedione) – Determination of diacetyl in workplace air using liquid chromatography (HPLC‐UV or HPLC‐MS)

This analytical method is a validated measurement procedure for the determination of 2,3‐butanedione (diacetyl) in workplace air in a concentration range of a tenth up to twice the currently valid Occupational Exposure Limit (OEL) or MAK value. Sampling is performed by drawing a defined volume of air through a cartridge filled with silica gel impregnated with 2,4‐dinitrophenylhydrazine (DNPH) using a suitable flow‐regulated pump with a volumetric flow rate of 1 mL/min. For sampling 1 hour or 15 min (checking the short‐term value) can be used. The formed diacetyl‐2,4‐DNPH derivatives are desorbed with acetonitrile containing a defined amount of DNPH and analysed by means of liquid chromatography (HPLC‐UV or HPLC‐MS). Quantitative evaluation is based on a 10‐point calibration using methacrolein‐2,4‐DNPH as internal standard. The limit of quantification for diacetyl is 0.002 mg/m3based on an air sample volume of approx. 60 L or 0.006 mg/m3based on an air sample volume of approx. 15 L (for short‐term value).
Xylol (alle Isomere), Addendum [BAT Value Documentation in German language, 2016]
Authors: Jäger T. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: October 2016

Addendum to Xylene (all isomers)

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for xylene and its isomers, considering xylene in blood and methylhippuric (toluric) acid (all isomers) to characterize the internal exposure. Xylene can easily pass through the skin, so biological monitoring is necessary for a valid individual risk assessment.

Xylene shows a fast elimination in the blood compartment. Thus, the concentration of xylene in blood is halved 30 minutes after the end of exposure. Therefore, sampling should be performed directly at the end of exposure. This is, however, difficult to realize in practice. Therefore, the BAT value for xylene (all isomers) in blood was withdrawn. Methylhippuric (toluric) acid in urine is available as a diagnostically specific parameter. The BAT value for methylhippuric acid is confirmed.
Dichlormethan, Addendum [BAT Value Documentation in German language, 2016]
Authors: Bolt H. M. , Weistenhöfer W. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: October 2016

Addendum to Dichloromethane

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dichloromethane, considering dichloromethane in blood to characterize the internal exposure.

In a chamber study, 14 non‐smokers were exposed to different concentrations of dichloromethane. After exposure to the present MAK‐value of 50 ml dichloromethane/m
3
without physical activity, a concentration of 0.3 mg dichloromethane/l blood was measured. Considering an increased intake due to elevated breathing volume during work, the exposure to 50 ml dichloromethane/m
3
results in a blood concentration of 0.5 mg/l. Taking into account this study and the EKA correlation of 2001, a BAT‐value of 500 µg dichloromethane/l blood was evaluated. Sampling time is straight after exposure.
Naphthalin [BAT Value Documentation in German language, 2016]
Authors: Klotz K. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: October 2016

Naphthalene

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated a BAR (“Biologischer Arbeitsstoff Referenzwert”) for naphthalene, considering 1‐ and 2‐naphthol in urine to characterize the internal exposure. Naphthalene is classified in category 2 for carcinogenic substances and designated with an “H” because of its contribution to the toxicological hazards due to penetration through the skin in vitro and dermal absorption in vivo.

In a number of biomonitoring studies, the excretion of 1‐ and 2‐naphthol in urine of persons occupationally not exposed to naphthalene was examined. Tobacco smoking affects the naphthol excretion significantly, thus non‐smokers and smokers have to be considered separately. Up to now, no data of representative collectives of the German general population are available. Therefore, the largest German study was considered for the evaluation, where urine samples of 95 non‐smokers were analysed and a 95th percentile for the sum of 1‐ and 2‐naphthol (after hydrolysis) of 33.6 µg/l (30.6 µg/g creatinine) was found. These results are in good accordance with other national and international studies. Therefore, a BAR of 35 µg 1‐ plus 2‐naphthol (after hydrolysis)/l urine was evaluated for non‐smokers. Sampling time is at the end of exposure or the end of the working shift and after long term exposure at the end of the working shift after several shifts. For the interpretation of the result, the smoking status of the persons has to be considered. In case of an occupational co‐exposure to other polycyclic aromatic hydrocarbons (PAH), the analysis of additional PAH‐metabolites is recommended (see MAK Documentation “Polycyclic Aromatic Hydrocarbons”).
β‐Hydroxyethoxyessigsäure (HEAA) in Urin [Biomonitoring Methods in German Language, 2015]
Authors: Leng G. , Gries W. , Göen T. , Bader M. , Eckert E. , Hartwig A. ,   MAK Commission
Published: October 2016

β‐Hydroxyethoxyacetic acid (HEAA) in urine

The documentation presents the selective detection of β‐hydroxyethoxyacetic acid (HEAA), which is considered to be the main metabolite of 1,4‐dioxane and diethylene glycol, respectively.

The urine sample to be analyzed is diluted with purified water and, after addition of the deuterated internal standard (D4‐HEAA), acidified with concentrated hydrochloric acid and then extracted with ethyl acetate. An aliquot of the ethyl acetate phase is evaporated to dryness under a stream of nitrogen. The residue is derivatized by addition of N‐methyl‐N‐(trimethylsilyl)trifluoroacetamide (MSTFA) and the bis‐silylated β‐hydroxyethoxyacetic acid is analyzed after electron impact ionization using GC–MS in the Selected Ion Monitoring (SIM) mode.
Ziram [MAK Value Documentation, 2015]
Authors: Hartwig A. ,   MAK Commission
Published: October 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated ziram to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect is inflammation, squamous metaplasia, hyperplasia, and necrosis of cartilage in the larynx of rats after 28‐day inhalation exposure to 0.3 mg/m
3
. From the NOAEC of 0.1 mg/m
3
a MAK value of 0.01 mg/m
3
for the inhalable fraction has been established. With the critical effect being local, ziram has been classified in Peak Limitation Category I. An excursion factor of 2 has been established as acute irritation is not expected if twice the MAK value is exceeded.

In one of three oral carcinogenicity studies in mice a significantly increased incidence of lung tumours was observed but coincided with a Sendai virus infection, therefore, this finding cannot unequivocally be regarded as substance‐induced. In one of three oral carcinogenicity studies in rats a significantly increased incidence of thyroid C‐cell carcinomas in male F344 rats was observed. As these tumours were not reproduced in other studies using higher doses and higher‐purity ziram and may have an incidence of up to 33% in untreated F344 rats, C‐cell carcinomas in male F344 rats are regarded as an isolated finding and have not resulted in the classification of ziram in one of the categories for carcinogenic substances.

Ziram did not demonstrate any mutagenicity in rats or mice or clastogenicity in mice.

The NOAEL for developmental toxicity accompanied by maternal toxicity was 16 mg/kg body weight and day in rats and 7.5 mg/kg body weight and day in rabbits, corresponding to ziram concentrations of 24 or 19 mg/m
3
. The NOAEL for developmental neurotoxicity was 12 mg/kg body weight and day, corresponding to 18 mg/m
3
. Thus, there is a sufficiently large margin between levels that cause developmental toxicity or developmental neurotoxicity and the MAK value of 0.01 mg ziram/m
3
I has been classified in Pregnancy Risk Group C.

Ziram shows a skin sensitizing potential in animals, which is also supported by the clinical and experimental findings obtained with the structurally closely‐related zinc diethyldithiocarbamate. Ziram has been labelled with “Sh” (for substances which cause sensitization of the skin), but not with “Sa” (for substances which cause sensitization of the airways).

Dermal absorption of ziram is low and does not contribute significantly to systemic toxicity.
Diacetyl [MAK Value Documentation, 2015]
Authors: Hartwig A. ,   MAK Commission
Published: October 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated diacetyl to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. The critical effects in popcorn workers exposed to diacetyl are subclinical changes in lung function, airway obstruction and bronchiolitis obliterans. That means diacetyl produces irreversible cumulative effects in the lungs. No effects on the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) of the workers were recorded at a cumulative exposure of 0.65 ml/m3 × year. Extrapolation of this value with Haber's Rule to occupational exposure for 40 years results in a value of 0.016 ml/m3. Effects on the nasal and respiratory epithel found in mice exposed for 12 weeks to diacetyl concentrations of 25 ml/m3do not contradict the effects on the lungs in workers exposed to diacetyl. The MAK value for diacetyl is derived on the basis of human data only, because humans have a higher sensitivity to diacetyl. A MAK value of 0.02 ml/m3is set. As the critical effect is a cumulative long‐term effect in the lungs, Peak Limitation Category II is assigned. To avoid triggering bronchiolitis obliterans by short‐term peak inhalation exposure an excursion factor of 1 is set. Skin contact may contribute significantly to systemic toxicity and diacetyl is designated with an “H” notation. Positive results from local lymph node assays in the mouse indicate that diacetyl has a low skin‐sensitizing potency. Because there is no developmental toxicity in hamsters, mice and rats, damage to the embryo or foetus is unlikely when the MAK value is observed and thus, diacetyl is classified in Pregnancy Risk Group C. In view of the genotoxicity of diacetyl in vitro and the local genotoxicity in vivo, local genotoxicity in the lungs is suspected; diacetyl is therefore classified in Carcinogen Category 3B.
Sex and seasonal differences in diet and nutrient intake in Verreaux's sifakas (Propithecus verreauxi)
Authors: Koch Flávia , Ganzhorn Joerg U. , Rothman Jessica M. , Chapman Colin A. , Fichtel Claudia
Published: October 2016

Fluctuations in food availability are a major challenge faced by primates living in seasonal climates. Variation in food availability can be especially challenging for females, because of the high energetic costs of reproduction. Therefore, females must adapt the particular demands of the different reproductive stages to the seasonal availability of resources. Madagascar has a highly seasonal climate, where food availability can be extremely variable. We investigated the seasonal changes in diet composition, nutrient and energy intake of female and male sifakas (Propithecus verreauxi) in a dry deciduous forest in western Madagascar. We examined how females adjust their diet to different reproductive stages. Seasonality affected the diet of both sexes; particularly in the dry season (Apr–Oct) with low availability of food items, especially fruits, males and females had a reduced nutrient and energy intake compared to the wet season (Nov–Mar) with higher food and fruit availability. The comparison of the diet between sexes in different reproductive stages showed that during the late stage of lactation (Nov–Jan) females had higher food intake, and as a result they had a higher intake of macronutrients (crude protein, fat and non‐structured carbohydrates (TNC)) and energy than males. These differences were not present during the pregnancy of females, with both sexes having similar intake of macronutrients and energy during that stage. The increase in the intake of macronutrients observed for females during late lactation could be related to the higher energetic demands of this stage of reproduction. Thus, the observed pattern in the diet indicates that sifaka females are following a capital breeding strategy, whereby females potentially store enough nutrients to cope with the reproduction costs in periods of low food availability.
Cyclo‐P4‐Bausteine – Verwirklichung nichtklassischer Fulleren‐Analogie und weiterer Topologien
Authors: Dielmann Fabian , Peresypkina Eugenia V. , Krämer Barbara , Hastreiter Florian , Johnson Brian P. , Zabel Manfred , Heindl Claudia , Scheer Manfred
Published: October 2016

Die cyclo‐P4‐Komplexe [CpRTa(CO)2(η4‐P4)] (CpR: Cp′′=1,3‐C5H3tBu2, Cp′′′=1,2,4‐C5H2tBu3) erweisen sich als prädestiniert zur Bildung von hohlen sphärischen Supramolekülen mit nichtklassischer Fulleren‐artiger Topologie. Die resultierenden Aggregate, die mittels CuX (X=Cl, Br) aufgebaut werden, zeigen ein hochsymmetrisches 32er‐Gerüst, das ausschließlich aus vier‐ und sechsgliedrigen Ringen aufgebaut ist. In einigen Supramolekülen ist der innere Hohlraum durch zusätzliche CuX‐Einheiten besetzt. Bei Verwendung von CuI werden zwei unterschiedliche Supramoleküle mit Erdnuss‐ oder Birnen‐förmigen Gerüsten und 2–2.5 nm Außendurchmesser isoliert. Weiterhin sind die sphärischen Supramoleküle mit Cp′′′‐substituierten Tantalkomplexen in CH2Cl2 löslich. NMR‐spektroskopische Untersuchungen in Lösung zeigen die Bildung von isomeren Supramolekülen infolge der sterischen Hinderung durch die dritte tBu‐Gruppe des Cp′′′‐Liganden. Zusätzlich wird ein 2D‐Koordinationspolymer erhalten und strukturell charakterisiert.
Slow Molecular Motions in Ionic Liquids Probed by Cross‐Relaxation of Nuclear Spins During Overhauser Dynamic Nuclear Polarization
Authors: Banerjee Abhishek , Dey Arnab , Chandrakumar Narayanan
Published: October 2016

Solution‐state Overhauser dynamic nuclear polarization (ODNP) at moderate fields, performed by saturating the electron spin resonance (ESR) of a free radical added to the sample of interest, is well known to lead to significant NMR signal enhancements in the steady state, owing to electron–nuclear cross‐relaxation. Here it is shown that under conditions which limit radical access to the molecules of interest, the time course of establishment of ODNP can provide a unique window into internuclear cross‐relaxation, and reflects relatively slow molecular motions. This behavior, modeled mathematically by a three‐spin version of the Solomon equations (one unpaired electron and two nuclear spins), is demonstrated experimentally on the 19F/1H system in ionic liquids. Bulky radicals in these viscous environments turn out to be just the right setting to exploit these effects. Compared to standard nuclear Overhauser effect (NOE) work, the present experiment offers significant improvement in dynamic range and sensitivity, retains usable chemical shift information, and reports on molecular motions in the sub‐megahertz (MHz) to tens of MHz range—motions which are not accessed at high fields.
Substratmodulierte reduktive Graphenfunktionalisierung
Authors: Schäfer Ricarda A. , Weber Konstantin , Koleśnik‐Gray Maria , Hauke Frank , Krstić Vojislav , Meyer Bernd , Hirsch Andreas
Published: October 2016

Die kovalente Funktionalisierung von mechanisch exfoliertem Graphenid‐Monolagen und ‐Bilagen auf SiO2‐Wafern mit λ‐Iodanen und anschließende Raman‐spektroskopische/‐mikroskopische Charakterisierung haben gezeigt, dass Graphen‐Monolagen bedeutend reaktiver sind als entsprechende Bilagen. Mittels unterstützender Dichtefunktionalrechnungen konnten wir zeigen, dass die ditope Addendenbindung zu sehr viel stabileren Produkten führt als die entsprechende monotope Reaktion. Dies kann durch die geringere Gitterspannung der Reaktionsprodukte erklärt werden. Die chemische Beschaffenheit des Substrats (Graphen oder SiO2) spielt dabei eine entscheidende Rolle.
Structural Snapshots for Mechanism‐Based Inactivation of a Glycoside Hydrolase by Cyclopropyl Carbasugars
Authors: Adamson Christopher , Pengelly Robert J. , Shamsi Kazem Abadi Saeideh , Chakladar Saswati , Draper Jason , Britton Robert , Gloster Tracey M. , Bennet Andrew J.
Published: October 2016

Glycoside hydrolases (GHs) have attracted considerable attention as targets for therapeutic agents, and thus mechanism‐based inhibitors are of great interest. We report the first structural analysis of a carbocyclic mechanism‐based GH inactivator, the results of which show that the two Michaelis complexes are in 2H3 conformations. We also report the synthesis and reactivity of a fluorinated analogue and the structure of its covalently linked intermediate (flattened 2H3 half‐chair). We conclude that these inactivator reactions mainly involve motion of the pseudo‐anomeric carbon atom, knowledge that should stimulate the design of new transition‐state analogues for use as chemical biology tools.
Hydrogen‐Abstraction/Acetylene‐Addition Exposed
Authors: Yang Tao , Troy Tyler P. , Xu Bo , Kostko Oleg , Ahmed Musahid , Mebel Alexander M. , Kaiser Ralf I.
Published: October 2016

Polycyclic aromatic hydrocarbons (PAHs) are omnipresent in the interstellar medium (ISM) and also in carbonaceous meteorites (CM) such as Murchison. However, the basic reaction routes leading to the formation of even the simplest PAH—naphthalene (C10H8)—via the hydrogen‐abstraction/acetylene‐addition (HACA) mechanism still remain ambiguous. Here, by revealing the uncharted fundamental chemistry of the styrenyl (C8H7) and the ortho‐vinylphenyl radicals (C8H7)—key transient species of the HACA mechanism—with acetylene (C2H2), we provide the first solid experimental evidence on the facile formation of naphthalene in a simulated combustion environment validating the previously postulated HACA mechanism for these two radicals. This study highlights, at the molecular level spanning combustion and astrochemistry, the importance of the HACA mechanism to the formation of the prototype PAH naphthalene.
Rich Athermal Ground‐State Chemistry Triggered by Dynamics through a Conical Intersection
Authors: Mignolet Benoit , Curchod Basile F. E. , Martínez Todd J.
Published: October 2016

A fundamental tenet of statistical rate theories (such as transition state theory and RRKM) is the rapidity of vibrational relaxation. Excited‐state reactions happen quite quickly (sub‐picosecond) and thus can exhibit nonstatistical behavior. However, it is often thought that any diversity of photoproducts results from different conical intersections connecting the excited and ground electronic states. It is also conceivable that the large energy of the photon, which is converted to vibrational energy after electronic transitions could lead to athermal hot ground state reactions and that these might be responsible for the diversity of photoproducts. Here we show that this is the case for sulfines, where a single conical intersection is implicated in the electronic transition but the excited state reaction leads to nine different products within less than a picosecond.
Terminal‐Selective Functionalization of Alkyl Chains by Regioconvergent Cross‐Coupling
Authors: Dupuy Stéphanie , Zhang Ke‐Feng , Goutierre Anne‐Sophie , Baudoin Olivier
Published: October 2016

Hydrocarbons are still the most important precursors of functionalized organic molecules, which has stirred interest in the discovery of new C−H bond functionalization methods. We describe herein a new step‐economical approach that enables C−C bonds to be constructed at the terminal position of linear alkanes. First, we show that secondary alkyl bromides can undergo in situ conversion into alkyl zinc bromides and regioconvergent Negishi coupling with aryl or alkenyl triflates. The use of a suitable phosphine ligand favoring Pd migration enabled the selective formation of the linear cross‐coupling product. Subsequently, mixtures of secondary alkyl bromides were prepared from linear alkanes by standard bromination, and regioconvergent cross‐coupling then provided access to the corresponding linear arylation product in only two steps.
Pseudo‐Contact NMR Shifts over the Paramagnetic Metalloprotein CoMMP‐12 from First Principles
Authors: Benda Ladislav , Mareš Jiří , Ravera Enrico , Parigi Giacomo , Luchinat Claudio , Kaupp Martin , Vaara Juha
Published: October 2016

Long‐range pseudo‐contact NMR shifts (PCSs) provide important restraints for the structure refinement of proteins when a paramagnetic metal center is present, either naturally or introduced artificially. Here we show that ab initio quantum‐chemical methods and a modern version of the Kurland–McGarvey approach for paramagnetic NMR (pNMR) shifts in the presence of zero‐field splitting (ZFS) together provide accurate predictions of all PCSs in a metalloprotein (high‐spin cobalt‐substituted MMP‐12 as a test case). Computations of 314 13C PCSs using g‐ and ZFS tensors based on multi‐reference methods provide a reliable bridge between EPR‐parameter‐ and susceptibility‐based pNMR formalisms. Due to the high sensitivity of PCSs to even small structural differences, local structures based either on X‐ray diffraction or on various DFT optimizations could be evaluated critically by comparing computed and experimental PCSs. Many DFT functionals provide insufficiently accurate structures. We also found the available 1RMZ PDB X‐ray structure to exhibit deficiencies related to binding of a hydroxamate inhibitor. This has led to a newly refined PDB structure for MMP‐12 (5LAB) that provides a more accurate coordination arrangement and PCSs.
cyclo‐P4 Building Blocks: Achieving Non‐Classical Fullerene Topology and Beyond
Authors: Dielmann Fabian , Peresypkina Eugenia V. , Krämer Barbara , Hastreiter Florian , Johnson Brian P. , Zabel Manfred , Heindl Claudia , Scheer Manfred
Published: October 2016

The cyclo‐P4 complexes [CpRTa(CO)2(η4‐P4)] (CpR: Cp′′=1,3‐C5H3tBu2, Cp′′′=1,2,4‐C5H2tBu3) turned out to be predestined for the formation of hollow spherical supramolecules with non‐classical fullerene‐like topology. The resulting assemblies constructed with CuX (X=Cl, Br) showed a highly symmetric 32‐vertex core of solely four‐ and six‐membered rings. In some supramolecules, the inner cavity was occupied by an additional CuX unit. On the other hand, using CuI, two different supramolecules with either peanut‐ or pear‐like shapes and outer diameters in the range of 2–2.5 nm were isolated. Furthermore, the spherical supramolecules containing Cp′′′ ligands at tantalum are soluble in CH2Cl2. NMR spectroscopic investigations in solution revealed the formation of isomeric supramolecules owing to the steric hindrance caused by the third tBu group on the Cp′′′ ligand. In addition, a 2D coordination polymer was obtained and structurally characterized.
Natural‐Product‐Inspired Aminoepoxybenzoquinones Kill Members of the Gram‐Negative Pathogen Salmonella by Attenuating Cellular Stress Response
Authors: Mandl Franziska A. , Kirsch Volker C. , Ugur Ilke , Kunold Elena , Vomacka Jan , Fetzer Christian , Schneider Sabine , Richter Klaus , Fuchs Thilo M. , Antes Iris , Sieber Stephan A.
Published: October 2016

Gram‐negative bacteria represent a challenging task for antibacterial drug discovery owing to their impermeable cell membrane and restricted uptake of small molecules. We herein describe the synthesis of natural‐product‐derived epoxycyclohexenones and explore their antibiotic activity against several pathogenic bacteria. A compound with activity against Salmonella Typhimurium was identified, and the target enzymes were unraveled by quantitative chemical proteomics. Importantly, two protein hits were linked to bacterial stress response, and corresponding assays revealed an elevated susceptibility to reactive oxygen species upon compound treatment. The consolidated inhibition of these targets provides a rationale for antibacterial activity and highlights epoxycyclohexenones as natural product scaffolds with suitable properties for killing Gram‐negative Salmonella.
Immobilization of a Bacterial Cytochrome P450 Monooxygenase System on a Solid Support
Authors: Tan Cheau Yuaan , Hirakawa Hidehiko , Suzuki Risa , Haga Tomoaki , Iwata Fumiya , Nagamune Teruyuki
Published: October 2016

Bacterial cytochrome P450s (P450s), which catalyze regio‐ and stereoselective oxidations of hydrocarbons with high turnover rates, are attractive biocatalysts for fine chemical production. Enzyme immobilization is needed for cost‐effective industrial manufacturing. However, immobilization of P450s is difficult because electron‐transfer proteins are involved in catalysis and anchoring these can prevent them from functioning as shuttle molecules for carrying electrons. We studied a heterotrimeric protein‐mediated co‐immobilization of a bacterial P450, and its electron‐transfer protein and reductase. Fusion with subunits of a heterotrimeric Sulfolobus solfataricus proliferating cell nuclear antigen (PCNA) enabled immobilization of the three proteins on a solid support. The co‐immobilized enzymes catalyzed monooxygenation because the electron‐transfer protein fused to PCNA via a single peptide linker retained its electron‐transport function.
Exploiting Host–Guest Interactions for the Synthesis of a Rod–Rod Block Copolymer with Crystalline and Liquid‐Crystalline Blocks
Authors: Zhou Feng , Gu Ke‐Hua , Zhang Zhen‐Yu , Zhang Meng‐Yao , Zhou Sheng , Shen Zhihao , Fan Xing‐He
Published: October 2016

By making use of the host–guest interactions between the host molecule tris‐o‐phenylenedioxycyclotriphosphazene (TPP) and the rod–coil block copolymer (BCP) poly(ethylene oxide)‐block‐poly(octyl 4′‐octyloxy‐2‐vinylbiphenyl‐4‐carboxylate) (PEO‐b‐PVBP), the supramolecular rod–rod block copolymer P(EO@TPP)‐b‐PVBP was constructed. It consists of a crystalline segment P(EO@TPP) with a hexagonal crystalline structure and a columnar nematic liquid‐crystalline segment (PVBP). As the PVBP segments arrange themselves as columnar nematic phases, the crystalline structure of the inclusion complex P(EO@TPP), which has a smaller diameter, is destroyed. The self‐assembled nanostructure is thus clearly affected by the interplay between the two blocks. On the basis of wide‐ and small‐angle X‐ray scattering analysis, we conclude that the supramolecular rod–rod BCP can self‐assemble into a cylinder‐in‐cylinder double hexagonal structure.
Bi−P Bond Homolysis as a Route to Reduced Bismuth Compounds and Reversible Activation of P4
Authors: Schwamm Ryan J. , Lein Matthias , Coles Martyn P. , Fitchett Christopher M.
Published: October 2016

Bismuth diphenylphosphanides Bi(NONR)(PPh2) (NONR=[O(SiMe2NR)2], R=tBu, 2,6‐iPr2C6H3, Aryl) undergo facile decomposition via single‐electron processes to form reduced Bi and P species. The corresponding derivatives Bi(NONR)(PCy2) are stable. Reaction of the isolated BiII radical .Bi(NONAr) with white phosphorus (P4) proceeds with the reversible and selective activation of a single P−P bond to afford the bimetallic μ,η1:1‐bicyclo[1.1.0]tetraphosphabutane compound.
Pyridyl‐Endcapped Polyynes: Stabilized Wire‐like Molecules
Authors: Krempe Maximilian , Lippert Rainer , Hampel Frank , Ivanović‐Burmazović Ivana , Jux Norbert , Tykwinski Rik R.
Published: October 2016

A 4‐ethynylpyridyl derivative with sterically shielding phenyl groups in the 3‐ and 5‐positions has been synthesized and used to terminate a series of polyynes. This approach allows for the synthesis of stable polyynes up to an octayne, twice as long as previous accessible for “unstabilized” pyridyl‐endcapped polyynes. The potential of these polyynes as wire‐like linkers to metal centers is demonstrated by axial coordination of pyridyl groups to zinc‐ and ruthenium‐metalloporphyrins.
Spectroscopic and X‐ray structural characterization of new polymeric organotin(IV) carboxylates and their in vitro antifungal activities: Part II
Authors: Rocha C.S. , de Morais B.P. , Rodrigues B.L. , Donnici C.L. , de Lima G.M. , Ardisson J.D. , Takahashi J.A. , Bitzer R.S.
Published: October 2016

The reactions of R3SnCl (R = Me, Bu or Ph) with sodium 4‐phenylbutyrate, Na(OPhb), in EtOH yielded three polymeric triorganotin carboxylates, namely [R3Sn(OPhb)]n (R = Me (1), Bu (2) or Ph (3)). All complexes were spectroscopically characterized using Fourier transform infrared, 119Sn Mössbauer, 1H NMR, 13C{1H} NMR and 119Sn{1H} NMR spectral techniques. In addition, the crystal structures of 1 and 3 were determined using single‐crystal X‐ray diffraction. Their polymeric structures are sustained by bridging carboxylates which connect two five‐coordinate Sn(IV) centres. Each metallic cation displays a distorted trigonal bipyramidal coordination geometry (Addison's parameters ranging from 0.84 in 1 to 0.77–0.91 in 3), with the oxygen atoms occupying the apical positions and the organic groups at the equatorial corners. The one‐dimensional zigzag chains of 1 propagate along the b‐axis, whereas 3 displays wave‐like double polymeric chains along the b‐axis. For both 1 and 3, parallel one‐dimensional polymeric chains are interconnected by C─H⋅⋅⋅π interactions. The antifungal activity of 1–3 was screened against Candida albicans (ATCC 18804), C. tropicalis (ATCC 750), C. glabrata (ATCC 90030), C. parapsilosis (ATCC 22019), C. lusitaniae (CBS 6936) and C. dubliniensis (clinical isolate 28). The antifungal activity of 3 was noteworthy since it was not only more active than 1 and 2, but also more active than the control drugs (nystatin and fluconazole nitrate) in some cases.
Preparation of polyamide 6/polystyrene quasi‐nanoblends by diffusion and subsequent polymerization of styrene in water‐sorbed polyamide 6 pellets
Authors: Huang Cheng‐Huan , Chen Fang , Guo Zhao‐Xia , Yu Jian
Published: October 2016

Polyamide 6 (PA6)/polystyrene (PS) blends with an average particle size of 103 nm were prepared by diffusion and subsequent polymerization of styrene in water‐sorbed PA6 pellets. The pretreatment of PA6 pellets in hot water is prerequisite for successful styrene diffusion. The diffusion process involves replacement of free water in the pellets by styrene, and should be carried out in neat styrene medium to provide concentration gradient between inside and outside of the pellets. The polymerization step was carried out in water medium with benzoic peroxide as the initiator. The diametrical distribution of PS in the blend pellets was investigated by Micro‐FTIR, and molecular weight of PS was measured by GPC. DSC measurements showed that the diffusion and polymerization of styrene occur in the amorphous regions of PA6 where the pre‐sorbed water locates. PA6/PS quasi‐nanoblends reported in this work cannot be obtained by conventional methods. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44554.
Direct electric current modifies important cellular aspects and ultrastructure features of Candida albicans yeasts: Influence of doses and polarities
Authors: Barbosa Gleyce Moreno , dos Santos Eldio Gonçalves , Capella Francielle Neves Carvalho , Homsani Fortune , de Pointis Marçal Carina , dos Santos Valle Roberta , de Araújo Abi‐Chacra Érika , Braga‐Silva Lys Adriana , de Oliveira Sales Marcelo Henrique , da Silva Neto Inácio Domingos , da Veiga Venicio Feo , dos Santos André Luis Souza , Holandino Carla
Published: October 2016

Available treatments against human fungal pathogens present high levels of resistance, motivating the development of new antifungal therapies. In this context, the present work aimed to analyze direct electric current (DC) antifungal action, using an in vitro apparatus equipped with platinum electrodes. Candida albicans yeast cells were submitted to three distinct conditions of DC treatment (anodic flow—AF; electroionic flow—EIF; and cathodic flow—CF), as well as different charges, ranging from 0.03 to 2.40 C. Our results indicated C. albicans presented distinct sensibility depending on the DC intensity and polarity applied. Both the colony‐forming unit assay and the cytometry flow with propidium iodide indicated a drastic reduction on cellular viability after AF treatment with 0.15 C, while CF‐ and EIF‐treated cells stayed alive when DC doses were increased up to 2.40 C. Additionally, transmission electron microscopy revealed important ultrastructural alterations in AF‐treated yeasts, including cell structure disorganization, ruptures in plasmatic membrane, and cytoplasmic rarefaction. This work emphasizes the importance of physical parameters (polarity and doses) in cellular damage, and brings new evidence for using electrotherapy to treat C. albicans pathology process. Bioelectromagnetics. 38:95–108, 2017. © 2016 Wiley Periodicals, Inc.
Function, not behavior, driving diagnosis and treatment of ASD in RDoC project
Authors: Oberman Lindsay M. , Jacob Suma
Published: October 2016

The World Health Organization defines mental disorders as qualitative abnormalities in thoughts, perceptions, emotions, behaviors, and relationships with others (http://www.who.int/mediacentre/factsheets/fs396/en/). Clinically, these disorders are described and differentiated based on categorical criteria (e.g., DSM or ICD categories). As biological influences on behavior are elucidated, categorical classifications for defining mental health disorders have come under increasing criticism (Clark et al., 1995; Hyman, 2010; Insel et al., 2010; Kendell & Jablensky, 2003; van Praag, 2000). Many core symptoms of different mental disorders overlap, and there is large heterogeneity in behavioral presentations within a given disorder. Factors including state‐dependent changes, environment, and development influence behavior at any given time and thus can impact clinical assessments and, in turn, treatment decisions. There can be unclear boundaries between psychopathology and normality, disorders can co‐occur, symptoms can overlap across disorders, and presentations change over time and development. This is especially evident in child psychiatry, where developmental trajectory, sensitive periods, and dynamic interactions between brain development and environment add additional variability to the clinical presentation. Development yields a wide distribution of “normal” or typical behaviors for any given age or level of development.
How self‐injury can lead to suicidality in teens: Under study
Authors: Knopf Alison
Published: October 2016

Both suicidality and nonsuicidal self‐injury (NSSI) among adolescents are serious concerns, but little is known about the level of suicidality in adolescents with a history of self‐injury. About 10% of adolescents in the community, and 35% in psychiatric patients, engage in NSSI. However, suicide ideation and attempts are less prevalent, with 12.1% of youth reporting ideation and 4.1% making at least one attempt. Suicidality and NSSI both increase from late childhood to adolescence, where they peak and then plateau or subside in early adulthood.
Free‐Standing NiO@C Nanobelt as an Efficient Catalyst for Water Splitting
Authors: Dong Qiuchun , Sun Chencheng , Dai Ziyang , Zang Xiaoxian , Dong Xiaochen
Published: October 2016

Cost‐effective and high‐efficiency electrocatalysts for water splitting are important for the production of renewable energy conversion and storage systems. Herein, a 3 D NiO nanobelt electrode was synthesized by direct oxidation of nickel foam using the hydrothermal method. Electrochemical studies reveal that the 3 D NiO nanobelt electrode exhibits excellent electrocatalytic activities for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) with low onset overpotential, small Tafel slope, and very eminent electrochemical stability in the standard aqueous solution of 1.0 m KOH. More importantly, the OER activity of 3 D NiO nanobelt can be enhanced by the wrapping of N‐doped carbon (NiO@C), which can achieve an overpotential of 500 mV at 100 mA cm−2, a low Tafel slope of 92 mV dec−1, and distinguished electrochemical stability. This strategy provides a general route to prepare 3 D nanostructured catalyst for water splitting by directly using transition‐metal foam as metal source and substrate.