bluuebunny/crossref_metadata_2025 huggingface dataset:
Gate-controlled conductance switching in DNA
Authors: Xiang Limin , Palma Julio L. , Li Yueqi , Mujica Vladimiro , Ratner Mark A. , Tao Nongjian
Published: February 2017

Extensive evidence has shown that long-range charge transport can occur along double helical DNA, but active control (switching) of single-DNA conductance with an external field has not yet been demonstrated. Here we demonstrate conductance switching in DNA by replacing a DNA base with a redox group. By applying an electrochemical (EC) gate voltage to the molecule, we switch the redox group between the oxidized and reduced states, leading to reversible switching of the DNA conductance between two discrete levels. We further show that monitoring the individual conductance switching allows the study of redox reaction kinetics and thermodynamics at single molecular level using DNA as a probe. Our theoretical calculations suggest that the switch is due to the change in the energy level alignment of the redox states relative to the Fermi level of the electrodes.
Scaffolding and completing genome assemblies in real-time with nanopore sequencing
Authors: Cao Minh Duc , Nguyen Son Hoang , Ganesamoorthy Devika , Elliott Alysha G. , Cooper Matthew A. , Coin Lachlan J. M.
Published: February 2017

Third generation sequencing technologies provide the opportunity to improve genome assemblies by generating long reads spanning most repeat sequences. However, current analysis methods require substantial amounts of sequence data and computational resources to overcome the high error rates. Furthermore, they can only perform analysis after sequencing has completed, resulting in either over-sequencing, or in a low quality assembly due to under-sequencing. Here we present npScarf, which can scaffold and complete short read assemblies while the long read sequencing run is in progress. It reports assembly metrics in real-time so the sequencing run can be terminated once an assembly of sufficient quality is obtained. In assembling four bacterial and one eukaryotic genomes, we show that npScarf can construct more complete and accurate assemblies while requiring less sequencing data and computational resources than existing methods. Our approach offers a time- and resource-effective strategy for completing short read assemblies.
Dissecting the molecular organization of the translocon-associated protein complex
Authors: Pfeffer Stefan , Dudek Johanna , Schaffer Miroslava , Ng Bobby G. , Albert Sahradha , Plitzko Jürgen M. , Baumeister Wolfgang , Zimmermann Richard , Freeze Hudson H. , Engel Benjamin D. , Förster Friedrich
Published: February 2017

In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum (ER) membrane by the ER protein translocon. The translocon-associated protein (TRAP) complex is an integral component of the translocon, assisting the Sec61 protein-conducting channel by regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography (CET) to study the structure of the native translocon in evolutionarily divergent organisms and disease-linked TRAP mutant fibroblasts from human patients. The structural differences detected by subtomogram analysis form a basis for dissecting the molecular organization of the TRAP complex. We assign positions to the four TRAP subunits within the complex, providing insights into their individual functions. The revealed molecular architecture of a central translocon component advances our understanding of membrane protein biogenesis and sheds light on the role of TRAP in human congenital disorders of glycosylation.
Strong electronic interaction and multiple quantum Hall ferromagnetic phases in trilayer graphene
Authors: Datta Biswajit , Dey Santanu , Samanta Abhisek , Agarwal Hitesh , Borah Abhinandan , Watanabe Kenji , Taniguchi Takashi , Sensarma Rajdeep , Deshmukh Mandar M.
Published: February 2017

Quantum Hall effect provides a simple way to study the competition between single particle physics and electronic interaction. However, electronic interaction becomes important only in very clean graphene samples and so far the trilayer graphene experiments are understood within non-interacting electron picture. Here, we report evidence of strong electronic interactions and quantum Hall ferromagnetism seen in Bernal-stacked trilayer graphene. Due to high mobility ∼500,000 cm2V−1s−1 in our device compared to previous studies, we find all symmetry broken states and that Landau-level gaps are enhanced by interactions; an aspect explained by our self-consistent Hartree–Fock calculations. Moreover, we observe hysteresis as a function of filling factor and spikes in the longitudinal resistance which, together, signal the formation of quantum Hall ferromagnetic states at low magnetic field.
Chromatin remodeller Fun30Fft3 induces nucleosome disassembly to facilitate RNA polymerase II elongation
Authors: Lee Junwoo , Shik Choi Eun , David Seo Hogyu , Kang Keunsoo , Gilmore Joshua M. , Florens Laurence , Washburn Michael P. , Choe Joonho , Workman Jerry L. , Lee Daeyoup
Published: February 2017

Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30Fft3 as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30Fft3 associates with RNAPII and collaborates with the histone chaperone, FACT, which facilitates RNAPII elongation through chromatin, to induce nucleosome disassembly at transcribing regions during RNAPII transcription. Mutants, resulting in reduced nucleosome-barrier, such as deletion mutants of histones H3/H4 themselves and the genes encoding components of histone deacetylase Clr6 complex II suppress the defects in growth and RNAPII occupancy of cells lacking Fun30Fft3. These data suggest that RNAPII utilizes the chromatin remodeller, Fun30Fft3, to overcome the nucleosome barrier to transcription elongation.
Portraying entanglement between molecular qubits with four-dimensional inelastic neutron scattering
Authors: Garlatti E. , Guidi T. , Ansbro S. , Santini P. , Amoretti G. , Ollivier J. , Mutka H. , Timco G. , Vitorica-Yrezabal I. J. , Whitehead G. F. S. , Winpenny R. E. P. , Carretta S.
Published: February 2017

Entanglement is a crucial resource for quantum information processing and its detection and quantification is of paramount importance in many areas of current research. Weakly coupled molecular nanomagnets provide an ideal test bed for investigating entanglement between complex spin systems. However, entanglement in these systems has only been experimentally demonstrated rather indirectly by macroscopic techniques or by fitting trial model Hamiltonians to experimental data. Here we show that four-dimensional inelastic neutron scattering enables us to portray entanglement in weakly coupled molecular qubits and to quantify it. We exploit a prototype (Cr7Ni)2 supramolecular dimer as a benchmark to demonstrate the potential of this approach, which allows one to extract the concurrence in eigenstates of a dimer of molecular qubits without diagonalizing its full Hamiltonian.
Layer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks
Authors: Bitzenhofer Sebastian H , Ahlbeck Joachim , Wolff Amy , Wiegert J. Simon , Gee Christine E. , Oertner Thomas G. , Hanganu-Opatz Ileana L.
Published: February 2017

Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta–gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout.
Effect of hydrogen on the integrity of aluminium–oxide interface at elevated temperatures
Authors: Li Meng , Xie De-Gang , Ma Evan , Li Ju , Zhang Xi-Xiang , Shan Zhi-Wei
Published: February 2017

Hydrogen can facilitate the detachment of protective oxide layer off metals and alloys. The degradation is usually exacerbated at elevated temperatures in many industrial applications; however, its origin remains poorly understood. Here by heating hydrogenated aluminium inside an environmental transmission electron microscope, we show that hydrogen exposure of just a few minutes can greatly degrade the high temperature integrity of metal–oxide interface. Moreover, there exists a critical temperature of ∼150 °C, above which the growth of cavities at the metal–oxide interface reverses to shrinkage, followed by the formation of a few giant cavities. Vacancy supersaturation, activation of a long-range diffusion pathway along the detached interface and the dissociation of hydrogen-vacancy complexes are critical factors affecting this behaviour. These results enrich the understanding of hydrogen-induced interfacial failure at elevated temperatures.
Both overlapping and independent mechanisms determine how diet and insulin-ligand knockouts extend lifespan of Drosophila melanogaster
Authors: Zandveld Jelle , van den Heuvel Joost , Zwaan Bastiaan J. , Piper Matthew D.W.
Published: February 2017

Lifespan in many organisms, including Drosophila melanogaster, can be increased by reduced insulin-IGF-like signaling (IIS) or by changes in diet. Most studies testing whether IIS is involved in diet-mediated lifespan extension employ only a few diets, but recent data shows that a broad range of nutritional environments is required. Here, we present lifespan data of long-lived Drosophila, lacking three of the eight insulin-like peptides [Drosophila insulin-like peptides 2,3,5 (dilp2-3,5)] on nine different diets that surround the optimum for lifespan. Their nutritional content was varied by manipulating sugar and yeast concentrations independently, and thus incorporated changes in both diet restriction and nutrient balance. The mutants were substantially longer-lived than controls on every diet, but the effects on the lifespan response to sugar and yeast differed. Our data illustrates how a greater coverage of diet balance (DB) and restriction can unify differing interpretations of how IIS might be involved in the response of lifespan to diet.
Spatial dynamics of TB within a highly urbanised Asian metropolis using point patterns
Authors: Das Sourav , Cook Alex R. , Wah Win , Win Khin Mar Kyi , Chee Cynthia Bin Eng , Wang Yee Tang , Yang Hsu Li
Published: February 2017

Singapore is a high-income country in a region with a high prevalence of tuberculosis. The Singapore Tuberculosis (TB) Elimination Program (STEP) was set up in 1997, and the better surveillance and clinical management practices initiated under STEP led to a decade-long decline in the incidence levels. However, incidence rates started to rise again since 2008. The reasons for this rise are unclear. This study involved a spatial analysis of the epidemiology of TB among Singapore residents. More than 30 000 cases reported during 1995–2011 and their residential addresses were analysed for spatial risk and spatial clustering, using spatial point pattern methodology. The principal factor responsible for the increasing resident TB incidence in Singapore is the changing age profile of the population. In particular the burgeoning population aged above 65 years accounts for the increase in reported cases. Singapore’s population has one of the world’s lowest fertility and mortality rates, and the elderly population is projected to grow substantially over the next few decades. Tuberculosis rates may therefore continue to rise even with static or improving case management and surveillance.
Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence
Authors: Zheng Hong-Yi , Zhang Ming-Xu , Chen Min , Jiang Jin , Song Jia-Hao , Lian Xiao-Dong , Tian Ren-Rong , Zhang Xiao-Liang , Zhang Lin-Tao , Pang Wei , Zhang Gao-Hong , Zheng Yong-Tang
Published: February 2017

The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4+ T cells. The low frequency of naïve CD4+ T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4+ T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression
Authors: Cho Sungrae , Roh Kangsan , Park Jaehyun , Park Yong Seok , Lee Minji , Cho Seungchan , Kil Eui-Joon , Cho Mun-Ju , Oh Jeong Su , Byun Hee-Seong , Cho Sang-Ho , Park Kyewon , Kang Hee , Koo Jinmo , Yeom Chang-Hwan , Lee Sukchan
Published: February 2017

Although surgery and radiation are beneficial for treating cancer, they can also lead to malfunctions of the lymphatic system such as secondary lymphedema. This abnormality of the lymphatic system is characterized by severe swelling, adipogenesis, inflammation, and fibrosis in the lymphedematous region. Moreover, the proliferation of fibrotic tissue in the lymphedematous region generates edema that is no longer spontaneously reversible. No treatment for fibrosis has been validated in patients with lymphedema. In our efforts to develop a therapeutic agent for lymphedema fibrosis, we used a newly established mouse hind limb model. Previous studies have demonstrated that hyaluronic acid accumulates in the lymphedematous region. Thus, we challenged mice with of hyaluronidase (HYAL), with the aim of reducing fibrogenesis. After subcutaneous injections in the lymphedematous mouse leg every two days, the volume of lymphedema had reduced significantly by 7 days post-operation. Histochemical analysis indicated that collagen accumulation and myofibroblast differentiation were decreased in epidermal tissues after HYAL injection. Moreover, it was associated with upregulation of interferon-gamma, increased numbers of Th1 cells, and downregulation of interleukin-4 and interleukin-6 in the lymphedematous region and spleen. These results indicate that hydrolysis of hyaluronic acid can boost an anti-fibrotic immune response in the mouse lymphedema model.
Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
Authors: Kang Jun Hyuk , Lee Ho-Sung , Park Daebeom , Kang Yun-Won , Kim Seon Myeong , Gong Jeong-Ryeol , Cho Kwang-Hyun
Published: February 2017

Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most of the findings were confined to particular experimental conditions corresponding to specific cellular contexts. A question then arises as to whether there might be essential regulatory interactions that prevail across diverse cellular contexts. To address this question, we have constructed a large-scale cardiac signaling network by integrating previous experimental results and developed a mathematical model using normalized ordinary differential equations. Specific cellular contexts were reflected to different kinetic parameters sampled from random distributions. Through extensive computer simulations with various parameter distributions, we revealed the five most essential context-independent regulatory interactions (between: (1) αAR and Gαq, (2) IP3 and calcium, (3) epac and CaMK, (4) JNK and NFAT, and (5) p38 and NFAT) for hypertrophy and apoptosis that were consistently found over all our perturbation analyses. These essential interactions are expected to be the most promising therapeutic targets across a broad spectrum of individual conditions of heart failure patients.
A Novel High-Density Phase and Amorphization of Nitrogen-Rich 1H-Tetrazole (CH2N4) under High Pressure
Authors: Li Wenbo , Huang Xiaoli , Bao Kuo , Zhao Zhonglong , Huang Yanping , Wang Lu , Wu Gang , Zhou Bo , Duan Defang , Li Fangfei , Zhou Qiang , Liu Bingbing , Cui Tian
Published: February 2017

The high-pressure behaviors of nitrogen-rich 1H-tetrazole (CH2N4) have been investigated by in situ synchrotron X-ray diffraction (XRD) and Raman scattering up to 75 GPa. A first crystalline-to-crystalline phase transition is observed and identified above ~3 GPa with a large volume collapse (∼18% at 4.4 GPa) from phase I to phase II. The new phase II forms a dimer-like structure, belonging to P1 space group. Then, a crystalline-to-amorphous phase transition takes place over a large pressure range of 13.8 to 50 GPa, which is accompanied by an interphase region approaching paracrystalline state. When decompression from 75 GPa to ambient conditions, the final product keeps an irreversible amorphous state. Our ultraviolet (UV) absorption spectrum suggests the final product exhibits an increase in molecular conjugation.
Performance, kinetic, and biodegradation pathway evaluation of anaerobic fixed film fixed bed reactor in removing phthalic acid esters from wastewater
Authors: Ahmadi Ehsan , Yousefzadeh Samira , Ansari Mohsen , Ghaffari Hamid Reza , Azari Ali , Miri Mohammad , Mesdaghinia Alireza , Nabizadeh Ramin , Kakavandi Babak , Ahmadi Peyman , Badi Mojtaba Yegane , Gholami Mitra , Sharafi Kiomars , Karimaei Mostafa , Ghoochani Mahboobeh , Brahmand Masoud Binesh , Mohseni Seyed Mohsen , Sarkhosh Maryam , Rezaei Soheila , Asgharnia Hosseinali , Dehghanifard Emad , Jafari Behdad , Mortezapour Alireza , Moghaddam Vahid Kazemi , Mahmoudi Mohammad Molla , Taghipour Nader
Published: February 2017

Emerging and hazardous environmental pollutants like phthalic acid esters (PAEs) are one of the recent concerns worldwide. PAEs are considered to have diverse endocrine disrupting effects on human health. Industrial wastewater has been reported as an important environment with high concentrations of PAEs. In the present study, four short-chain PAEs including diallyl phthalate (DAP), diethyl phthalate (DEP), dimethyl phthalate (DMP), and phthalic acid (PA) were selected as a substrate for anaerobic fixed film fixed bed reactor (AnFFFBR). The process performances of AnFFFBR, and also its kinetic behavior, were evaluated to find the best eco-friendly phthalate from the biodegradability point of view. According to the results and kinetic coefficients, removing and mineralizing of DMP occurred at a higher rate than other phthalates. In optimum conditions 92.5, 84.41, and 80.39% of DMP, COD, and TOC were removed. DAP was found as the most bio-refractory phthalate. The second-order (Grau) model was selected as the best model for describing phthalates removal.
Mutations underlying Episodic Ataxia type-1 antagonize Kv1.1 RNA editing
Authors: Ferrick-Kiddie Elizabeth A. , Rosenthal Joshua J. C. , Ayers Gregory D. , Emeson Ronald B.
Published: February 2017

Adenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele. Editing of transcripts encoding mutant channels affects numerous biophysical properties including channel opening, closing, and inactivation. Thus EA1 symptoms could be influenced not only by the direct effects of the mutations on channel properties, but also by their influence on RNA editing. These studies provide the first evidence that mutations associated with human genetic disorders can affect cis-regulatory elements to alter RNA editing.
Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development
Authors: Dengler Christopher G. , Yue Cuiyong , Takano Hajime , Coulter Douglas A.
Published: February 2017

In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses.
Durability-enhanced two-dimensional hole gas of C-H diamond surface for complementary power inverter applications
Authors: Kawarada Hiroshi , Yamada Tetsuya , Xu Dechen , Tsuboi Hidetoshi , Kitabayashi Yuya , Matsumura Daisuke , Shibata Masanobu , Kudo Takuya , Inaba Masafumi , Hiraiwa Atsushi
Published: February 2017

Complementary power field effect transistors (FETs) based on wide bandgap materials not only provide high-voltage switching capability with the reduction of on-resistance and switching losses, but also enable a smart inverter system by the dramatic simplification of external circuits. However, p-channel power FETs with equivalent performance to those of n-channel FETs are not obtained in any wide bandgap material other than diamond. Here we show that a breakdown voltage of more than 1600 V has been obtained in a diamond metal-oxide-semiconductor (MOS) FET with a p-channel based on a two-dimensional hole gas (2DHG). Atomic layer deposited (ALD) Al2O3 induces the 2DHG ubiquitously on a hydrogen-terminated (C-H) diamond surface and also acts as both gate insulator and passivation layer. The high voltage performance is equivalent to that of state-of-the-art SiC planar n-channel FETs and AlGaN/GaN FETs. The drain current density in the on-state is also comparable to that of these two FETs with similar device size and VB.
The X-like shaped spatiotemporal structure of the biphoton entangled state in a cold two-level atomic ensemble
Authors: Zhang Dasen , Zhang Zhiming
Published: February 2017

We study the spatiotemporal structure of the biphoton entangled state generated by the four-wave mixing (FWM) process in a cold two-level atomic ensemble. We analyze, for the first time, the X-like shaped structure of the biphoton entangled state and the geometry of the biphoton correlation for different lengths and densities of the cold atomic ensemble. The propagation equations of the photon pairs generated from FWM process are derived in a spatiotemporal framework. By means of the input-output relations of the propagation equations, the biphoton amplitude function is obtained in a spatiotemporal domain. In the given frequency range, the biphoton amplitude displays an X-like shaped geometry, nonfactorizable in the space-time domain. Such an X-like shaped spatiotemporal structure is caused by the phase matching and the FWM gain. The former leads to the X-like shaped envelope of the biphoton correlation, while the latter gives rise to the oscillations around the X-like shaped envelope.
Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization
Authors: Degani-Katzav Nurit , Klein Moshe , Har-Even Moran , Gortler Revital , Tobi Ruthi , Paas Yoav
Published: February 2017

Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the C. elegans heteromeric GluClα/β receptor, it cannot activate a homomeric receptor composed of the C. elegans GluClβ subunits. To understand this incapability, we generated a homopentameric α7-GluClβ chimeric receptor that consists of an extracellular ligand-binding domain of an α7 nicotinic acetylcholine receptor known to be potentiated by IVM, and a chloride-selective channel domain assembled from GluClβ subunits. Application of IVM prior to acetylcholine inhibited the responses of the chimeric α7-GluClβR. Adding IVM to activated α7-GluClβRs, considerably accelerated the decline of ACh-elicited currents and stabilized the receptors in a non-conducting state. Determination of IVM association and dissociation rate constants and recovery experiments suggest that, following initial IVM binding to open α7-GluClβRs, the drug induces a conformational change and locks the ion channel in a closed state for a long duration. We further found that IVM also inhibits the activation by glutamate of a homomeric receptor assembled from the C. elegans full-length GluClβ subunits.
Nonlinear infrared spectroscopy free from spectral selection
Authors: Paterova Anna , Lung Shaun , Kalashnikov Dmitry A. , Krivitsky Leonid A.
Published: February 2017

Infrared (IR) spectroscopy is an indispensable tool for many practical applications including material analysis and sensing. Existing IR spectroscopy techniques face challenges related to the inferior performance and the high cost of IR-grade components. Here, we develop a new method, which allows studying properties of materials in the IR range using only visible light optics and detectors. It is based on the nonlinear interference of entangled photons, generated via Spontaneous Parametric Down Conversion (SPDC). In our interferometer, the phase of the signal photon in the visible range depends on the phase of an entangled IR photon. When the IR photon is traveling through the media, its properties can be found from observations of the visible photon. We directly acquire the SPDC signal with a visible range CCD camera and use a numerical algorithm to infer the absorption coefficient and the refraction index of the sample in the IR range. Our method does not require the use of a spectrometer and a slit, thus it allows achieving higher signal-to-noise ratio than the earlier developed method.
Multi-Constituent Simulation of Thrombus Deposition
Authors: Wu Wei-Tao , Jamiolkowski Megan A. , Wagner William R. , Aubry Nadine , Massoudi Mehrdad , Antaki James F.
Published: February 2017

In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.
Rapid and sensitive diagnoses of dry root rot pathogen of chickpea (Rhizoctonia bataticola (Taub.) Butler) using loop-mediated isothermal amplification assay
Authors: Ghosh Raju , Tarafdar Avijit , Sharma Mamta
Published: February 2017

Dry root rot (DRR) caused by the fungus Rhizoctonia bataticola (Taub.) Butler, is an emerging disease in chickpea. The disease is often mistaken with other root rots like Fusarium wilt, collar rot and black root rot in chickpea. Therefore, its timely and specific detection is important. Current detection protocols are either based on mycological methods or on protocols involving DNA amplification by polymerase chain reaction (PCR). Here we report the rapid and specific detection of R. bataticola using loop-mediated isothermal amplification (LAMP) assay targeting fungal specific 5.8S rDNA sequence for visual detection of R. bataticola. The reaction was optimized at 63 °C for 75 min using minimum 10 fg of DNA. After adding SYBR Green I in LAMP products, the amplification was found to be highly specific in all the 94 isolates of R. bataticola collected from diverse geographical regions as well as DRR infected plants and sick soil. No reaction was found in other pathogenic fungi infecting chickpea (Fusarium oxysporum f. sp. ciceris, Rhizoctonia solani, Sclerotium rolfsii and Fusarium solani) and pigeonpea (Fusarium udum and Phytophthora cajani). The standardised LAMP assay with its simplicity, rapidity and specificity is very useful for the visual detection of this emerging disease in chickpea.
Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening
Authors: Temml Veronika , Garscha Ulrike , Romp Erik , Schubert Gregor , Gerstmeier Jana , Kutil Zsofia , Matuszczak Barbara , Waltenberger Birgit , Stuppner Hermann , Werz Oliver , Schuster Daniela
Published: February 2017

Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation. Targeting both LT biosynthesis and the conversion of EETs with a dual inhibitor of FLAP and sEH may represent a novel, powerful anti-inflammatory strategy. We present a pharmacophore-based virtual screening campaign that led to 20 hit compounds of which 4 targeted FLAP and 4 were sEH inhibitors. Among them, the first dual inhibitor for sEH and FLAP was identified, N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N’-(3,4-dichlorophenyl)urea with IC50 values of 200 nM in a cell-based FLAP test system and 20 nM for sEH activity in a cell-free assay.
Development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system
Authors: Nie Jianhui , Wu Xiaohong , Ma Jian , Cao Shouchun , Huang Weijin , Liu Qiang , Li Xuguang , Li Yuhua , Wang Youchun
Published: February 2017

Pseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications. We developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method. Employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-virus based assays. Compared with current rapid fluorescent focus inhibition test (RFFIT), our in vitro pseudovirus-based neutralization assay (PBNA) is much less labor-intensive while demonstrating better reproducibility. Moreover, the in vivo PBNA assay was also found to be superior to the live virus based assay. Following intravenous administration, the pseudovirus effectively infected the mice, with dynamic viral distributions being sequentially observed in spleen, liver and brain. Furthermore, data from in vivo PBNA showed great agreement with those generated from the live virus model but with the experimental time significantly reduced from 2 weeks to 3 days. Taken together, the effective pseudovirus production system facilitated the development of novel PBNA assays which could replace live virus-based traditional assays due to its safety, rapidity, reproducibility and high throughput capacity.
Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control
Authors: Valenza Gaetano , Citi Luca , Garcia Ronald G. , Taylor Jessica Noggle , Toschi Nicola , Barbieri Riccardo
Published: February 2017

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.
Calcium spikes, waves and oscillations in a large, patterned epithelial tissue
Authors: Balaji Ramya , Bielmeier Christina , Harz Hartmann , Bates Jack , Stadler Cornelia , Hildebrand Alexander , Classen Anne-Kathrin
Published: February 2017

While calcium signaling in excitable cells, such as muscle or neurons, is extensively characterized, calcium signaling in epithelial tissues is little understood. Specifically, the range of intercellular calcium signaling patterns elicited by tightly coupled epithelial cells and their function in the regulation of epithelial characteristics are little explored. We found that in Drosophila imaginal discs, a widely studied epithelial model organ, complex spatiotemporal calcium dynamics occur. We describe patterns that include intercellular waves traversing large tissue domains in striking oscillatory patterns as well as spikes confined to local domains of neighboring cells. The spatiotemporal characteristics of intercellular waves and oscillations arise as emergent properties of calcium mobilization within a sheet of gap-junction coupled cells and are influenced by cell size and environmental history. While the in vivo function of spikes, waves and oscillations requires further characterization, our genetic experiments suggest that core calcium signaling components guide actomyosin organization. Our study thus suggests a possible role for calcium signaling in epithelia but importantly, introduces a model epithelium enabling the dissection of cellular mechanisms supporting the initiation, transmission and regeneration of long-range intercellular calcium waves and the emergence of oscillations in a highly coupled multicellular sheet.
Organic/Organic Heterointerface Engineering to Boost Carrier Injection in OLEDs
Authors: Fathollahi Mohammadreza , Ameri Mohsen , Mohajerani Ezeddin , Mehrparvar Ebrahim , Babaei Mohammadrasoul
Published: February 2017

We investigate dynamic formation of nanosheet charge accumulations by heterointerface engineering in double injection layer (DIL) based organic light emitting diodes (OLEDs). Our experimental results show that the device performance is considerably improved for the DIL device as the result of heterointerface injection layer (HIIL) formation, in comparison to reference devices, namely, the current density is doubled and even quadrupled and the turn-on voltage is favorably halved, to 3.7 V, which is promising for simple small-molecule OLEDs. The simulation reveals the (i) formation of dynamic p-type doping (DPD) region which treats the quasi Fermi level at the organic/electrode interface, and (ii) formation of dynamic dipole layer (DDL) and the associated electric field at the organic/organic interface which accelerates the ejection of the carriers and their transference to the successive layer. HIIL formation proposes alternate scenarios for device design. For instance, no prerequisite for plasma treatment of transparent anode electrode, our freedom in varying the thicknesses of the organic layers between 10 nm and 60 nm for the first layer and between 6 nm and 24 nm for the second layer. The implications of the present work give insight into the dynamic phenomena in OLEDs and facilitates the development of their inexpensive fabrication for lighting applications.
Matrix attachment region combinations increase transgene expression in transfected Chinese hamster ovary cells
Authors: Zhao Chun-Peng , Guo Xiao , Chen Si-Jia , Li Chang-Zheng , Yang Yun , Zhang Jun-He , Chen Shao-Nan , Jia Yan-Long , Wang Tian-Yun
Published: February 2017

Matrix attachment regions (MARs) are cis-acting DNA elements that can increase transgene expression levels in a CHO cell expression system. To investigate the effects of MAR combinations on transgene expression and the underlying regulatory mechanisms, we generated constructs in which the enhanced green fluorescent protein (eGFP) gene flanked by different combinations of human β-interferon and β-globin MAR (iMAR and gMAR, respectively), which was driven by the cytomegalovirus (CMV) or simian virus (SV) 40 promoter. These were transfected into CHO-K1 cells, which were screened with geneticin; eGFP expression was detected by flow cytometry. The presence of MAR elements increased transfection efficiency and transient and stably expression of eGFP expression under both promoters; the level was higher when the two MARs differed (i.e., iMAR and gMAR) under the CMV but not the SV40 promoter. For the latter, two gMARs showed the highest activity. We also found that MARs increased the ratio of stably transfected positive colonies. These results indicate that combining the CMV promoter with two different MAR elements or the SV40 promoter with two gMARs is effective for inducing high expression level and stability of transgenes.
Discrete Element Model for Suppression of Coffee-Ring Effect
Authors: Xu Ting , Lam Miu Ling , Chen Ting-Hsuan
Published: February 2017

When a sessile droplet evaporates, coffee-ring effect drives the suspended particulate matters to the droplet edge, eventually forming a ring-shaped deposition. Because it causes a non-uniform distribution of solid contents, which is undesired in many applications, attempts have been made to eliminate the coffee-ring effect. Recent reports indicated that the coffee-ring effect can be suppressed by a mixture of spherical and non-spherical particles with enhanced particle-particle interaction at air-water interface. However, a model to comprehend the inter-particulate activities has been lacking. Here, we report a discrete element model (particle system) to investigate the phenomenon. The modeled dynamics included particle traveling following the capillary flow with Brownian motion, and its resultant 3D hexagonal close packing of particles along the contact line. For particles being adsorbed by air-water interface, we modeled cluster growth, cluster deformation, and cluster combination. We found that the suppression of coffee-ring effect does not require a circulatory flow driven by an inward Marangoni flow at air-water interface. Instead, the number of new cluster formation, which can be enhanced by increasing the ratio of non-spherical particles and the overall number of microspheres, is more dominant in the suppression process. Together, this model provides a useful platform elucidating insights for suppressing coffee-ring effect for practical applications in the future.
Control of terahertz nonlinear transmission with electrically gated graphene metadevices
Authors: Choi Hyun Joo , Baek In Hyung , Kang Bong Joo , Kim Hyeon-Don , Oh Sang Soon , Hamm Joachim M. , Pusch Andreas , Park Jagang , Lee Kanghee , Son Jaehyeon , Jeong Young U. k. , Hess Ortwin , Rotermund Fabian , Min Bumki
Published: February 2017

Graphene, which is a two-dimensional crystal of carbon atoms arranged in a hexagonal lattice, has attracted a great amount of attention due to its outstanding mechanical, thermal and electronic properties. Moreover, graphene shows an exceptionally strong tunable light-matter interaction that depends on the Fermi level - a function of chemical doping and external gate voltage - and the electromagnetic resonance provided by intentionally engineered structures. In the optical regime, the nonlinearities of graphene originated from the Pauli blocking have already been exploited for mode-locking device applications in ultrafast laser technology, whereas nonlinearities in the terahertz regime, which arise from a reduction in conductivity due to carrier heating, have only recently been confirmed experimentally. Here, we investigated two key factors for controlling nonlinear interactions of graphene with an intense terahertz field. The induced transparencies of graphene can be controlled effectively by engineering meta-atoms and/or changing the number of charge carriers through electrical gating. Additionally, nonlinear phase changes of the transmitted terahertz field can be observed by introducing the resonances of the meta-atoms.
Long-term satellite tracking reveals variable seasonal migration strategies of basking sharks in the north-east Atlantic
Authors: Doherty P. D. , Baxter J. M. , Gell F. R. , Godley B. J. , Graham R. T. , Hall G. , Hall J. , Hawkes L. A. , Henderson S. M. , Johnson L. , Speedie C. , Witt M. J.
Published: February 2017

Animal migration is ubiquitous in nature with individuals within a population often exhibiting varying movement strategies. The basking shark (Cetorhinus maximus) is the world’s second largest fish species, however, a comprehensive understanding of their long-term wider-ranging movements in the north-east Atlantic is currently lacking. Seventy satellite tags were deployed on basking sharks over four years (2012–2015) off the west coast of Scotland and the Isle of Man. Data from 28 satellite tags with attachment durations of over 165 days reveal post-summer ranging behaviours. Tagged sharks moved a median minimum straight-line distance of 3,633 km; achieving median displacement of 1,057 km from tagging locations. Tagged individuals exhibited one of three migration behaviours: remaining in waters of UK, Ireland and the Faroe Islands; migrating south to the Bay of Biscay or moving further south to waters off the Iberian Peninsula, and North Africa. Sharks used both continental shelf areas and oceanic habitats, primarily in the upper 50–200 m of the water column, spanning nine geo-political zones and the High Seas, demonstrating the need for multi-national cooperation in the management of this species across its range.
Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6
Authors: Huang Jo-Hsi , Ku Wei-Chi , Chen Yen-Chun , Chang Yi-Ling , Chu Chia-Ying
Published: February 2017

DDX6 is a conserved DEAD-box protein (DBP) that plays central roles in cytoplasmic RNA regulation, including processing body (P-body) assembly, mRNA decapping, and translational repression. Beyond its cytoplasmic functions, DDX6 may also have nuclear functions because its orthologues are known to localize to nuclei in several biological contexts. However, it is unclear whether DDX6 is generally present in human cell nuclei, and the molecular mechanism underlying DDX6 subcellular distribution remains elusive. In this study, we showed that DDX6 is commonly present in the nuclei of human-derived cells. Our structural and molecular analyses deviate from the current model that the shuttling of DDX6 is directly mediated by the canonical nuclear localization signal (NLS) and nuclear export signal (NES), which are recognized and transported by Importin-α/β and CRM1, respectively. Instead, we show that DDX6 can be transported by 4E-T in a piggyback manner. Furthermore, we provide evidence for a novel nuclear targeting mechanism in which DDX6 enters the newly formed nuclei by “hitch-hiking” on mitotic chromosomes with its C-terminal domain during M phase progression. Together, our results indicate that the nucleocytoplasmic localization of DDX6 is regulated by these dual mechanisms.