bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Cav3.2 channels
Authors: Proft Juliane , Rzhepetskyy Yuriy , Lazniewska Joanna , Zhang Fang-Xiong , Cain Stuart M. , Snutch Terrance P. , Zamponi Gerald W. , Weiss Norbert
Published: September 2017

Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Cav3.2 channel to modulate the sorting of the channel to the cell surface. We demonstrate that the GAERS missense mutation located in the Cav3.2 III-IV linker alters the Cav3.2/calnexin interaction, resulting in an increased surface expression of the channel and a concomitant elevation in calcium influx. Our study reveals a novel mechanism that controls the expression of T-type channels, and provides a molecular explanation for the enhancement of T-type calcium conductance in GAERS.
Voice selectivity in the temporal voice area despite matched low-level acoustic cues
Authors: Agus Trevor R. , Paquette Sébastien , Suied Clara , Pressnitzer Daniel , Belin Pascal
Published: September 2017

In human listeners, the temporal voice areas (TVAs) are regions of the superior temporal gyrus and sulcus that respond more to vocal sounds than a range of nonvocal control sounds, including scrambled voices, environmental noises, and animal cries. One interpretation of the TVA’s selectivity is based on low-level acoustic cues: compared to control sounds, vocal sounds may have stronger harmonic content or greater spectrotemporal complexity. Here, we show that the right TVA remains selective to the human voice even when accounting for a variety of acoustical cues. Using fMRI, single vowel stimuli were contrasted with single notes of musical instruments with balanced harmonic-to-noise ratios and pitches. We also used “auditory chimeras”, which preserved subsets of acoustical features of the vocal sounds. The right TVA was preferentially activated only for the natural human voice. In particular, the TVA did not respond more to artificial chimeras preserving the exact spectral profile of voices. Additional acoustic measures, including temporal modulations and spectral complexity, could not account for the increased activation. These observations rule out simple acoustical cues as a basis for voice selectivity in the TVAs.
Late-stage differentiation of embryonic pancreatic β-cells requires Jarid2
Authors: Cervantes Sara , Fontcuberta-PiSunyer Marta , Servitja Joan-Marc , Fernandez-Ruiz Rebeca , García Ainhoa , Sanchez Lidia , Lee Young-Sook , Gomis Ramon , Gasa Rosa
Published: September 2017

Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation. Inactivation of Jarid2 in endocrine progenitors demonstrates that Jarid2 functions after endocrine specification. Furthermore, genome-wide expression analysis reveals that Jarid2 is required for the complete activation of the insulin-producing β-cell differentiation program. Jarid2-deficient pancreases exhibit impaired deposition of RNAPII-Ser5P, the initiating form of RNAPII, but no changes in H3K27me3, at the promoters of affected endocrine genes. Thus, our study identifies Jarid2 as a fine-tuner of gene expression during late stages of pancreatic endocrine cell development. These findings are relevant for generation of transplantable stem cell-derived β-cells.
Cleavage of 3′-terminal adenosine by archaeal ATP-dependent RNA ligase
Authors: Yoshinari Shigeo , Liu Yancheng , Gollnick Paul , Ho C. Kiong
Published: September 2017

Methanothermobacter thermoautotrophicus RNA ligase (MthRnl) catalyzes formation of phosphodiester bonds between the 5′-phosphate and 3′-hydroxyl termini of single-stranded RNAs. It can also react with RNA with a 3′-phosphate end to generate a 2′,3′-cyclic phosphate. Here, we show that MthRnl can additionally remove adenosine from the 3′-terminus of the RNA to produce 3′-deadenylated RNA, RNA(3′-rA). This 3′-deadenylation activity is metal-dependent and requires a 2′-hydroxyl at both the terminal adenosine and the penultimate nucleoside. Residues that contact the ATP/AMP in the MthRnl crystal structures are essential for the 3′-deadenylation activity, suggesting that 3′-adenosine may occupy the ATP-binding pocket. The 3′-end of cleaved RNA(3′-rA) consists of 2′,3′-cyclic phosphate which protects RNA(3′-rA) from ligation and further deadenylation. These findings suggest that ATP-dependent RNA ligase may act on a specific set of 3′-adenylated RNAs to regulate their processing and downstream biological events.
Rewiring of neuronal networks during synaptic silencing
Authors: Wrosch Jana Katharina , Einem Vicky von , Breininger Katharina , Dahlmanns Marc , Maier Andreas , Kornhuber Johannes , Groemer Teja Wolfgang
Published: September 2017

Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro. This method enables the calculation of network parameters, such as propagation probability, path length, and clustering behavior through the measurement of synaptic activity at the single-cell level, thus providing a fuller understanding of how changes at single synapses translate to an entire population of neurons. We demonstrate that our methodology can detect the known effects of drug-induced neuronal inactivity and can be used to investigate the extensive rewiring processes affecting population-wide connectivity patterns after periods of induced neuronal inactivity.
Electron beam detection of a Nanotube Scanning Force Microscope
Authors: Siria Alessandro , Niguès Antoine
Published: September 2017

Atomic Force Microscopy (AFM) allows to probe matter at atomic scale by measuring the perturbation of a nanomechanical oscillator induced by near-field interaction forces. The quest to improve sensitivity and resolution of AFM forced the introduction of a new class of resonators with dimensions at the nanometer scale. In this context, nanotubes are the ultimate mechanical oscillators because of their one dimensional nature, small mass and almost perfect crystallinity. Coupled to the possibility of functionalisation, these properties make them the perfect candidates as ultra sensitive, on-demand force sensors. However their dimensions make the measurement of the mechanical properties a challenging task in particular when working in cavity free geometry at ambient temperature. By using a focused electron beam, we show that the mechanical response of nanotubes can be quantitatively measured while approaching to a surface sample. By coupling electron beam detection of individual nanotubes with a custom AFM we image the surface topography of a sample by continuously measuring the mechanical properties of the nanoresonators. The combination of very small size and mass together with the high resolution of the electron beam detection method offers unprecedented opportunities for the development of a new class of nanotube-based scanning force microscopy.
Effects of Coarse Graining and Saturation of Hydrocarbon Chains on Structure and Dynamics of Simulated Lipid Molecules
Authors: Buslaev Pavel , Gushchin Ivan
Published: September 2017

Molecular dynamics simulations are used extensively to study the processes on biological membranes. The simulations can be conducted at different levels of resolution: all atom (AA), where all atomistic details are provided; united atom (UA), where hydrogen atoms are treated inseparably of corresponding heavy atoms; and coarse grained (CG), where atoms are grouped into larger particles. Here, we study the behavior of model bilayers consisting of saturated and unsaturated lipids DOPC, SOPC, OSPC and DSPC in simulations performed using all atom CHARMM36 and coarse grained Martini force fields. Using principal components analysis, we show that the structural and dynamical properties of the lipids are similar, both in AA and CG simulations, although the unsaturated molecules are more dynamic and favor more extended conformations. We find that CG simulations capture 75 to 100% of the major collective motions, overestimate short range ordering, result in more flexible molecules and 5–7 fold faster sampling. We expect that the results reported here will be useful for comprehensive quantitative comparisons of simulations conducted at different resolution levels and for further development and improvement of CG force fields.
Luminophore Configuration and Concentration-Dependent Optoelectronic Characteristics of a Quantum Dot-Embedded DNA Hybrid Thin film
Authors: Arasu Velu , Dugasani Sreekantha Reddy , Kesama Mallikarjuna Reddy , Chung Ho Kyoon , Park Sung Ha
Published: September 2017

To be useful in optoelectronic devices and sensors, a platform comprising stable fluorescence materials is essential. Here we constructed quantum dots (QDs) embedded DNA thin films which aims for stable fluorescence through the stabilization of QDs in the high aspect ratio salmon DNA (SDNA) matrix. Also for maximum luminescence, different concentration and configurations of core- and core/alloy/shell-type QDs were embedded within SDNA. The QD-SDNA thin films were constructed by drop-casting and investigated their optoelectronic properties. The infrared, UV-visible and photoluminescence (PL) spectroscopies confirm the embedment of QDs in the SDNA matrix. Absolute PL quantum yield of the QD-SDNA thin film shows the ~70% boost due to SDNA matrix compared to QDs alone in aqueous phase. The linear increase of PL photon counts from few to order of 5 while increasing [QD] reveals the non-aggregation of QDs within SDNA matrix. These systematic studies on the QD structure, absorbance, and concentration- and thickness-dependent optoelectronic characteristics demonstrate the novel properties of the QD-SDNA thin film. Consequently, the SDNA thin films were suggested to utilize for the generalised optical environments, which has the potential as a matrix for light conversion and harvesting nano-bio material as well as for super resolution bioimaging- and biophotonics-based sensors.
Identification of stiffness-induced signalling mechanisms in cells from patent and fused sutures associated with craniosynostosis
Authors: Barreto Sara , González-Vázquez Arlyng , R. Cameron Andrew , O’Brien Fergal J. , Murray Dylan J.
Published: September 2017

Craniosynostosis is a bone developmental disease where premature ossification of the cranial sutures occurs leading to fused sutures. While biomechanical forces have been implicated in craniosynostosis, evidence of the effect of microenvironmental stiffness changes in the osteogenic commitment of cells from the sutures is lacking. Our aim was to identify the differential genetic expression and osteogenic capability between cells from patent and fused sutures of children with craniosynostosis and whether these differences are driven by changes in the stiffness of the microenvironment. Cells from both sutures demonstrated enhanced mineralisation with increasing substrate stiffness showing that stiffness is a stimulus capable of triggering the accelerated osteogenic commitment of the cells from patent to fused stages. The differences in the mechanoresponse of these cells were further investigated with a PCR array showing stiffness-dependent upregulation of genes mediating growth and bone development (TSHZ2, IGF1), involved in the breakdown of extracellular matrix (MMP9), mediating the activation of inflammation (IL1β) and controlling osteogenic differentiation (WIF1, BMP6, NOX1) in cells from fused sutures. In summary, this study indicates that stiffer substrates lead to greater osteogenic commitment and accelerated bone formation, suggesting that stiffening of the extracellular environment may trigger the premature ossification of the sutures.
Broadband acoustic skin cloak based on spiral metasurfaces
Authors: Wang Xu , Mao Dongxing , Li Yong
Published: September 2017

A skin cloak based on the acoustic metasurface made of graded spiral units is proposed and numerically investigated. The presented skin cloak is an acoustical layer consisting of 80 subwavelength-sized unit cells, which provide precise local phase modulation and hence resort the disturbed sound filed in such a way to hide the object to acoustic wave. Numerical simulations show that the suggested skin cloak both work well under normal and small-angled incidences. By taking the advantage of the spiral-typed metasurface, the suggested skin cloak is rather thin with thickness in the order around 1/7 of the wavelength of target frequency, moreover, the intrinsic characteristics of modest dispersion ensure the skin cloak provides remarkable acoustic invisibility in a broad frequency ranging from 2500 Hz to 3600 Hz.
Detailed Balance Limit of Efficiency of Broadband-Pumped Lasers
Authors: Nechayev Sergey , Rotschild Carmel
Published: September 2017

Broadband light sources are a wide class of pumping schemes for lasers including LEDs, sunlight and flash lamps. Recently, efficient coupling of broadband light to high-quality micro-cavities has been demonstrated for on-chip applications and low-threshold solar-pumped lasers via cascade energy transfer. However, the conversion of incoherent to coherent light comes with an inherent price of reduced efficiency, which has yet to be assessed. In this paper, we derive the detailed balance limit of efficiency of broadband-pumped lasers and discuss how it is affected by the need to maintain a threshold population inversion and thermodynamically dictated minimal Stokes’ shift. We show that lasers’ slope efficiency is analogous to the nominal efficiency of solar cells, limited by thermalisation losses and additional unavoidable Stokes’ shift. The lasers’ power efficiency is analogous to the detailed balance limit of efficiency of solar cells, affected by the cavity mirrors and impedance matching factor, respectively. As an example we analyze the specific case of solar-pumped sensitized Nd3+:YAG-like lasers and define the conditions to reach their thermodynamic limit of efficiency. Our work establishes an upper theoretical limit for the efficiency of broadband-pumped lasers. Our general, yet flexible model also provides a way to incorporate other optical and thermodynamic losses and, hence, to estimate the efficiency of non-ideal broadband-pumped lasers.
Phylogeography of the sand dollar genus Encope: implications regarding the Central American Isthmus and rates of molecular evolution
Authors: Coppard Simon E. , Lessios H. A.
Published: September 2017

Vicariant events have been widely used to calibrate rates of molecular evolution, the completion of the Central American Isthmus more extensively than any other. Recent studies have claimed that rather than the generally accepted date of ~3 million years ago (Ma), the Isthmus was effectively complete by the middle Miocene, 13 Ma. We present a fossil calibrated phylogeny of the new world sand dollar genus Encope, based on one nuclear and four mitochondrial genes, calibrated with fossils at multiple nodes. Present day distributions of Encope are likely the result of multiple range contractions and extinction events. Most species are now endemic to a single region, but one widely distributed species in each ocean is composed of morphotypes previously described as separate species. The most recent separation between eastern Pacific and Caribbean extant clades occurred at 4.90 Ma, indicating that the Isthmus of Panama allowed genetic exchange until the Pliocene. The rate of evolution of mitochondrial genes in Encope has been ten times slower than in the closely related genera Mellita and Lanthonia. This large difference in rates suggests that splits between eastern Pacific and Caribbean biota, dated on the assumption of a “universal” mitochondrial DNA clock are not valid.
Selective antibody activation through protease-activated pro-antibodies that mask binding sites with inhibitory domains
Authors: Chen I-Ju , Chuang Chih-Hung , Hsieh Yuan-Chin , Lu Yun-Chi , Lin Wen-Wei , Huang Chien-Chiao , Cheng Ta-Chun , Cheng Yi-An , Cheng Kai-Wen , Wang Yeng-Tseng , Chen Fang-Ming , Cheng Tian-Lu , Tzou Shey-Cherng
Published: September 2017

Systemic injection of therapeutic antibodies may cause serious adverse effects due to on-target toxicity to the antigens expressed in normal tissues. To improve the targeting selectivity to the region of disease sites, we developed protease-activated pro-antibodies by masking the binding sites of antibodies with inhibitory domains that can be removed by proteases that are highly expressed at the disease sites. The latency-associated peptide (LAP), C2b or CBa of complement factor 2/B were linked, through a substrate peptide of matrix metalloproteinase-2 (MMP-2), to an anti-epidermal growth factor receptor (EGFR) antibody and an anti-tumor necrosis factor-α (TNF-α) antibody. Results showed that all the inhibitory domains could be removed by MMP-2 to restore the binding activities of the antibodies. LAP substantially reduced (53.8%) the binding activity of the anti-EGFR antibody on EGFR-expressing cells, whereas C2b and CBa were ineffective (21% and 9.3% reduction, respectively). Similarly, LAP also blocked 53.9% of the binding activity of the anti-TNF-α antibody. Finally, molecular dynamic simulation showed that the masking efficiency of LAP, C2b and CBa was 33.7%, 10.3% and −5.4%, respectively, over the binding sites of the antibodies. This strategy may aid in designing new protease-activated pro-antibodies that attain high therapeutic potency yet reduced systemic on-target toxicity.
Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors
Authors: Manasa Justen , Varghese Vici , Pond Sergei L. Kosakovsky , Rhee Soo-Yon , Tzou Philip L. , Fessel W. Jeffrey , Jang Karen S. , White Elizabeth , Rögnvaldsson Thorsteinn , Katzenstein David A. , Shafer Robert W.
Published: September 2017

Several groups have proposed that genotypic determinants in gag and the gp41 cytoplasmic domain (gp41-CD) reduce protease inhibitor (PI) susceptibility without PI-resistance mutations in protease. However, no gag and gp41-CD mutations definitively responsible for reduced PI susceptibility have been identified in individuals with virological failure (VF) while receiving a boosted PI (PI/r)-containing regimen. To identify gag and gp41 mutations under selective PI pressure, we sequenced gag and/or gp41 in 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen. We quantified nonsynonymous and synonymous changes in both genes and identified sites exhibiting signal for directional or diversifying selection. We also used published gag and gp41 polymorphism data to highlight mutations displaying a high selection index, defined as changing from a conserved to an uncommon amino acid. Many amino acid mutations developed in gag and in gp41-CD in both the PI- and NNRTI-treated groups. However, in neither gene, were there discernable differences between the two groups in overall numbers of mutations, mutations displaying evidence of diversifying or directional selection, or mutations with a high selection index. If gag and/or gp41 encode PI-resistance mutations, they may not be confined to consistent mutations at a few sites.
Cadmium effects on DNA and protein metabolism in oyster (Crassostrea gigas) revealed by proteomic analyses
Authors: Meng Jie , Wang Wenxiong , Li Li , Yin Qi , Zhang Guofan
Published: September 2017

Marine molluscs, including oysters, can concentrate high levels of cadmium (Cd) in their soft tissues, but the molecular mechanisms of Cd toxicity remain speculative. In this study, Pacific oysters (Crassostrea gigas) were exposed to Cd for 9 days and their gills were subjected to proteomic analysis, which were further confirmed with transcriptomic analysis. A total of 4,964 proteins was quantified and 515 differentially expressed proteins were identified in response to Cd exposure. Gene Ontology enrichment analysis revealed that excess Cd affected the DNA and protein metabolism. Specifically, Cd toxicity resulted in the inhibition of DNA glycosylase and gap-filling and ligation enzymes expressions in base excision repair pathway, which may have decreased DNA repair capacity. At the protein level, Cd induced the heat shock protein response, initiation of protein refolding as well as degradation by ubiquitin proteasome pathway, among other effects. Excess Cd also induced antioxidant responses, particularly glutathione metabolism, which play important roles in Cd chelation and anti-oxidation. This study provided the first molecular mechanisms of Cd toxicity on DNA and protein metabolism at protein levels, and identified molecular biomarkers for Cd toxicity in oysters.
Multisegmented Nanowires: a Step towards the Control of the Domain Wall Configuration
Authors: Berganza E. , Jaafar M. , Bran C. , Fernández-Roldán J. A. , Chubykalo-Fesenko O. , Vázquez M. , Asenjo A.
Published: September 2017

Cylindrical nanowires synthesized by controlled electrodeposition constitute excellent strategic candidates to engineer magnetic domain configurations. In this work, multisegmented CoNi/Ni nanowires are synthesized for tailoring a periodic magnetic structure determined by the balance between magnetocrystalline and magnetostatic energies. High-resolution Transmission Electron Microscopy confirms the segmented growth and the sharp transition between layers. Although both CoNi and Ni segments have similar fcc cubic crystal symmetry, their magnetic configuration is quite different as experimentally revealed by Magnetic Force Microscopy (MFM) imaging. While the Ni segments are single domain with axial magnetization direction, the CoNi segments present two main configurations: a single vortex state or a complex multivortex magnetic configuration, which is further interpreted with the help of micromagnetic simulations. This original outcome is ascribed to the tight competition between anisotropies. The almost monocrystalline fcc structure of the CoNi segments, as revealed by the electron diffraction patterns, which is atypical for its composition, contributes to balance the magnetocrystalline and shape anisotropies. The results of MFM measurements performed under in-plane magnetic field demonstrate that it is possible to switch from the multivortex configuration to a single vortex configuration with low magnetic fields.
Exposure to genetically engineered olive fly (Bactrocera oleae) has no negative impact on three non-target organisms
Authors: Marubbi Thea , Cassidy Clare , Miller Esther , Koukidou Martha , Martin-Rendon Enca , Warner Simon , Loni Augusto , Beech Camilla
Published: September 2017

Bactrocera oleae (Diptera: Tephritidae) remains a major pest of olive fruit production worldwide. Current pest management programs largely depend on chemical insecticides, resulting in high economic and environmental costs. Alternative pest control approaches are therefore highly desirable. We have created a conditional female-specific self-limiting strain of B. oleae (OX3097D-Bol) that could be applied for sustainable pest control. OX3097D-Bol olive fly carries a fluorescent marker (DsRed2) for identification and a self-limiting genetic trait that is repressed by tetracycline. In the absence of tetracycline, the tetracycline transactivator (tTAV) accumulates, resulting in female death at larvae and early pupal stages. The aim of this study was to evaluate the impact of genetically engineered OX3097D-Bol olive fly on three non-target organisms that either predate or parasitize olive flies, one from the guild of parasitoids (Psyttalia concolor) and two from the guild of predators (Pardosa spider species and the rove beetle Aleochara bilineata). No significant negative effect was observed on life history parameters, mortality and reproductive capacity of the non-target organisms studied. These results suggest that potential exposure to DsRed2 and tTAV gene products (e.g. mRNA and encoded proteins) would have a negligible impact on on-target organisms in the guilds or predators and parasitoids.
On current transients in MoS2 Field Effect Transistors
Authors: Macucci Massimo , Tambellini Gerry , Ovchinnikov Dmitry , Kis Andras , Iannaccone Giuseppe , Fiori Gianluca
Published: September 2017

We present an experimental investigation of slow transients in the gate and drain currents of MoS2-based transistors. We focus on the measurement of both the gate and drain currents and, from the comparative analysis of the current transients, we conclude that there are at least two independent trapping mechanisms: trapping of charges in the silicon oxide substrate, occurring with time constants of the order of tens of seconds and involving charge motion orthogonal to the MoS2 sheet, and trapping at the channel surface, which occurs with much longer time constants, in particular when the device is in a vacuum. We observe that the presence of such slow phenomena makes it very difficult to perform reliable low-frequency noise measurements, requiring a stable and repeatable steady-state bias point condition, and may explain the sometimes contradictory results that can be found in the literature about the dependence of the flicker noise power spectral density on gate bias.
Complete reperfusion is required for maximal benefits of mechanical thrombectomy in stroke patients
Authors: Chamorro Ángel , Blasco Jordi , López Antonio , Amaro Sergio , Román Luis San , Llull Laura , Renú Arturo , Rudilosso Salvatore , Laredo Carlos , Obach Victor , Urra Xabier , Planas Anna M. , Leira Enrique C. , Macho Juan
Published: September 2017

A mTICI 2b or a mTICI 3 score are currently considered success following mechanical thrombectomy (MT) in acute stroke but is undetermined whether the two scores translate equivalent outcomes. We present a single-center, retrospective cohort of patients with anterior circulation stroke treated with MT and achieving a final mTICI score 2b or 3. A multimodal CT at baseline and a multimodal MRI at 24 hours assessed the growth of the infarct, and the modified Rankin Scale (mRS) assessed functional outcome at 90 days. The primary outcome was the shift analysis of the mRS at day 90 in ordinal regression adjusted for covariates (age, sex, pretreatment NIHSS score, target occlusion, infarct core, pretreatment alteplase), and the collateral score. Infarct growth was explored in a similarly adjusted multiple linear regression model. MT was started within a median of 285 minutes of symptom onset; 51 (41%) patients achieved a mTICI 2b, and 74 (59%), a mTICI 3. mTICI 3 resulted in better mRS score transitions than mTICI 2b (odds ratio 2.018 [95% CI 1.033–3.945], p = 0. 040), and reduced infarct growth (p = 0.002). We conclude that in patients with acute stroke receiving MT, success should be redefined as achieving a mTICI 3 score.
Transcranial direct current stimulation (tDCS) applied to the left dorsolateral premotor cortex (dPMC) interferes with rhythm reproduction
Authors: Pollok B. , Overhagen C. L. , Keitel A. , Krause V.
Published: September 2017

Movement timing in the sub-second range engages a brain network comprising cortical and sub-cortical areas. The present study aims at investigating the functional significance of the left dorsolateral premotor cortex (dPMC) for precise movement timing as determined by sensorimotor synchronization and rhythm reproduction. To this end, 18 healthy volunteers performed an auditorily paced synchronization-continuation task with the right hand. A simple reaction time task served as control condition. Transcranial direct current stimulation (tDCS) was applied over the left dPMC in order to modulate cortical excitability either with anodal or cathodal polarity or as sham stimulation. TDCS was applied for 10 minutes, respectively on separate days. For the continuation task the analysis revealed significantly smaller inter-tap intervals (ITIs) following cathodal tDCS suggesting movement hastening as well as a trend towards larger ITIs following anodal stimulation suggesting movement slowing. No significant effect was found following sham stimulation. Neither for synchronization nor for reaction time tasks significant polarity-specific effects emerged. The data suggest the causal involvement of the dPMC in temporally precisereproduction of isochronous rhythms rather than sensorimotor synchronization. The present findings support the hypothesis that different cortical brain areas within the motor-control-network distinctively contribute to movement timing in the sub-second range.
Kinetic adaptation of human Myo19 for active mitochondrial transport to growing filopodia tips
Authors: Ušaj Marko , Henn Arnon
Published: September 2017

Myosins are actin-based molecular motors which are enzymatically adapted for their cellular functions such as transportation and membrane tethering. Human Myo19 affects mitochondrial motility, and promotes their localization to stress-induced filopodia. Therefore, studying Myo19 enzymology is essential to understand how this motor may facilitate mitochondrial motility. Towards this goal, we have purified Myo19 motor domain (Myo19-3IQ) from a human-cell expression system and utilized transient kinetics to study the Myo19-3IQ ATPase cycle. We found that Myo19-3IQ exhibits noticeable conformational changes (isomerization steps) preceding both ATP and ADP binding, which may contribute to nucleotide binding r﻿egulation. Notably, the ADP isomerization step and subsequent ADP release contribute significantly to the rate-limiting step of the Myo19-3IQ ATPase cycle. Both the slow ADP isomerization and ADP release prolong the time Myo19-3IQ spend in the strong actin binding state and hence contribute to its relatively high duty ratio. However, the predicted duty ratio is lower than required to support motility as a monomer. Therefore, it may be that several Myo19 motors are required to propel mitochondria movement on actin filaments efficiently. Finally, we provide a model explaining how Myo19 translocation may be regulated by the local ATP/ADP ratio, coupled to the mitochondria presence in the filopodia.
Role of tumor necrosis factor–α and its receptors in diesel exhaust particle-induced pulmonary inflammation
Authors: Kumar Smitha , Joos Guy , Boon Louis , Tournoy Kurt , Provoost Sharen , Maes Tania
Published: September 2017

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung. However, the underlying mechanisms remain to be elucidated. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that operates by binding to tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). The role of TNF-α signaling and the importance of either TNFR1 or TNFR2 in the DEP-induced inflammatory response has not yet been elucidated. TNF-α knockout (KO), TNFR1 KO, TNFR2 KO, TNFR1/TNFR2 double KO (TNFR-DKO) and wild type (WT) mice were intratracheally exposed to saline or DEP. Pro-inflammatory cells and cytokines were assessed in the bronchoalveolar lavage fluid (BALF). Exposure to DEP induced a dose-dependent inflammation in the BALF in WT mice. In addition, levels of TNF-α and its soluble receptors were increased upon exposure to DEP. The DEP-induced inflammation in the BALF was decreased in TNF-α KO, TNFR-DKO and TNFR2 KO mice. In contrast, the inflammatory response in the BALF of DEP-exposed TNFR1 KO mice was largely comparable with WT controls. In conclusion, these data provide evidence for a regulatory role of TNF-α in DEP-induced pulmonary inflammation and identify TNFR2 as the most important receptor in mediating these inflammatory effects.
Coprophagous features in carnivorous Nepenthes plants: a task for ureases
Authors: Yilamujiang Ayufu , Zhu Anting , Ligabue-Braun Rodrigo , Bartram Stefan , Witte Claus-Peter , Hedrich Rainer , Hasabe Mitsuyasu , Schöner Caroline R. , Schöner Michael G. , Kerth Gerald , Carlini Célia R. , Mithöfer Axel
Published: September 2017

Most terrestrial carnivorous plants are specialized on insect prey digestion to obtain additional nutrients. Few species of the genus Nepenthes developed mutualistic relationships with mammals for nitrogen supplementation. Whether dietary changes require certain enzymatic composition to utilize new sources of nutrients has rarely been tested. Here, we investigated the role of urease for Nepenthes hemsleyana that gains nitrogen from the bat Kerivoula hardwickii while it roosts inside the pitchers. We hypothesized that N. hemsleyana is able to use urea from the bats’ excrements. In fact, we demonstrate that 15N-enriched urea provided to Nepenthes pitchers is metabolized and its nitrogen is distributed within the plant. As ureases are necessary to degrade urea, these hydrolytic enzymes should be involved. We proved the presence and enzymatic activity of a urease for Nepenthes plant tissues. The corresponding urease cDNA from N. hemsleyana was isolated and functionally expressed. A comprehensive phylogenetic analysis for eukaryotic ureases, including Nepenthes and five other carnivorous plants’ taxa, identified them as canonical ureases and reflects the plant phylogeny. Hence, this study reveals ureases as an emblematic example for an efficient, low-cost but high adaptive plasticity in plants while developing a further specialized lifestyle from carnivory to coprophagy.
Time-resolved analysis of DNA-protein interactions in living cells by UV laser pulses
Authors: Nebbioso Angela , Benedetti Rosaria , Conte Mariarosaria , Carafa Vincenzo , De Bellis Floriana , Shaik Jani , Matarese Filomena , Della Ventura Bartolomeo , Gesuele Felice , Velotta Raffaele , Martens Joost H. A. , Stunnenberg Hendrik G. , Altucci Carlo , Altucci Lucia
Published: September 2017

Interactions between DNA and proteins are mainly studied through chemical procedures involving bi-functional reagents, mostly formaldehyde. Chromatin immunoprecipitation is used to identify the binding between transcription factors (TFs) and chromatin, and to evaluate the occurrence and impact of histone/DNA modifications. The current bottleneck in probing DNA-protein interactions using these approaches is caused by the fact that chemical crosslinkers do not discriminate direct and indirect bindings or short-lived chromatin occupancy. Here, we describe a novel application of UV laser-induced (L-) crosslinking and demonstrate that a combination of chemical and L-crosslinking is able to distinguish between direct and indirect DNA-protein interactions in a small number of living cells. The spatial and temporal dynamics of TF bindings to chromatin and their role in gene expression regulation may thus be assessed. The combination of chemical and L-crosslinking offers an exciting and unprecedented tool for biomedical applications.
Changes in CD73, CD39 and CD26 expression on T-lymphocytes of ANCA-associated vasculitis patients suggest impairment in adenosine generation and turn-over
Authors: Kling Lovis , Benck Urs , Breedijk Annette , Leikeim Lisa , Heitzmann Marianne , Porubsky Stefan , Krämer Bernhard K. , Yard Benito A. , Kälsch Anna-Isabelle
Published: September 2017

Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) patients, an impaired expression of these molecules on T-cells of AAV patients was hypothesized in the present study. While in AAV patients (n = 29) CD26 was increased on CD4+lymphocytes, CD39 and CD73 were generally reduced on patients’ T-cells. In CD4+cells significant differences in CD73 expression were confined to memory CD45RA-cells, while in CD4-lymphocytes differences were significant in both naïve CD45RA+and memory CD45RA-cells. The percentage of CD4-CD73+cells correlated with micro-RNA (miR)−31 expression, a putative regulator of factor inhibiting hypoxia-inducible factor 1 alpha (FIH-1), inversely with serum C-reactive protein (CRP) and positively with estimated glomerular filtration rate (eGFR). No correlation with disease activity, duration, and ANCA profile was found. It remains to be assessed if a decreased CD73 and CD39 expression underlies functional impairment of lymphocytes in AAV patients. Likewise, the relations between frequencies of CD4-CD73+cells and serum CRP or eGFR require further functional elucidation.
Differential regulation of vaginal lipocalins (OBP, MUP) during the estrous cycle of the house mouse
Authors: Černá Martina , Kuntová Barbora , Talacko Pavel , Stopková Romana , Stopka Pavel
Published: September 2017

Female house mice produce pheromone-carrying major urinary proteins (MUPs) in a cycling manner, thus reaching the maximum urinary production just before ovulation. This is thought to occur to advertise the time of ovulation via deposited urine marks. This study aimed to characterize the protein content from the house mouse vaginal flushes to detect putative vaginal-advertising molecules for a direct identification of reproductive states. Here we show that the mouse vaginal discharge contains lipocalins including those from the odorant binding (OBP) and major urinary (MUP) protein families. OBPs were highly expressed but only slightly varied throughout the cycle, whilst several MUPs were differentially abundant. MUP20 or ‘darcin’, was thought to be expressed only by males. However, in females it was significantly up-regulated during estrus similarly as the recently duplicated central/group-B MUPs (sMUP17 and highly expressed sMUP9), which in the mouse urine are male biased. MUPs rise between proestrus and estrus, remain steady throughout metestrus, and are co-expressed with antimicrobial proteins. Thus, we suggest that MUPs and potentially also OBPs are important components of female vaginal advertising of the house mouse.
SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential of Single-Walled Carbon Nanotube-Exposed Cells
Authors: Voronkova Maria A. , Luanpitpong Sudjit , Rojanasakul Liying Wang , Castranova Vincent , Dinu Cerasela Zoica , Riedel Heimo , Rojanasakul Yon
Published: September 2017

Engineered nanomaterials hold great promise for the future development of innovative products but their adverse health effects are a major concern. Recent studies have indicated that certain nanomaterials, including carbon nanotubes (CNTs), may be carcinogenic. However, the underlying mechanisms behind their potential malignant properties remain unclear. In this study, we linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs). We found that SOX9 is upregulated in SWCNT-exposed cells, which is consistent with their abilities to induce tumor formation and metastasis in vivo. We therefore hypothesized that SOX9 overexpression may be responsible for the neoplastic-like phenotype observed in our model. Indeed, SOX9 knockdown inhibited anchorage-independent cell growth in vitro and lung colonization in vivo in a mouse xenograft model. SOX9 depletion also suppressed the formation of cancer stem-like cells (CSCs), as determined by tumor sphere formation and aldehyde dehydrogenase (ALDH) activity (Aldefluor) assays. Furthermore, SOX9 knockdown suppressed tumor metastasis and the expression of the stem cell marker ALDH1A1. Taken together, our findings provide a mechanistic insight into SWCNT-induced carcinogenesis and the role of SOX9 in CSC regulation and metastasis.
Low temperature plasma promoting fibroblast proliferation by activating the NF-κB pathway and increasing cyclinD1 expression
Authors: Liu Jin-Ren , Xu Gui-Min , Shi Xing-Min , Zhang Guan-Jun
Published: September 2017

The potential applications of low temperature plasma (LTP) in wound healing have aroused the concern of many researchers. In this study, an argon atmospheric pressure plasma jet was applied to generate LTP for treatment of murine fibroblast cell (L929) culturedin vitroto investigate the effect of NF-κB pathway on fibroblast proliferation. The results showed that, compared with the control, L929 cells treated with plasma for less than 20 s had significant increases of proliferation; the productions of intracellular ROS, O2−and NO increased with prolongation of LTP treatment time; NF-κB pathway was activated by LTP in a proper dose range, and the expression of cyclinD1 in LTP-treated cells increased with the same trend as cell proliferation. After RNA interference to block p65 expression, with the same treatment time, RNAi-treated cells proliferated more slowly and expressed less cyclinD1 than normal cells. Furthermore, pretreatment with N-acetyl-L-cysteine (NAC) markedly prevented the plasma-induced changes in cells. In conclusion, the proliferation of L929 cells induced by LTP was closely related to NF-κB signaling pathway, which might be activated by appropriate level of intracellular ROS. These novel findings can provide some theoretical reference of LTP inducing cell proliferation and promoting wound healing.
Plasmon-Coupled Whispering Gallery Modes on Nanodisk Arrays for Signal Enhancements
Authors: Kang Tae Young , Lee Wonju , Ahn Heesang , Shin Dong-Myeong , Kim Chang-Seok , Oh Jin-Woo , Kim Donghyun , Kim Kyujung
Published: September 2017

Metallic nanostructures including single and double nanodisks are successfully used to enhance the localized electric field in vicinity of microcavity in whispering gallery mode (WGM) sensor. We demonstrate numerical calculations of plasmonic coupling of WGMs to single and double nanodisk arrays on a planar substrate. We then experimentally confirmed that the resonance wavelength of WGM sensor was dramatically shifted by adoption of single and double nanodisks on the surface of microcavity in the WGM sensor. Thus, our approach provides the tunable sensitivity of WGM sensor, and has a great potential to be used in numerous areas where the single biomolecule, protein-protein folding and biomolecular interactions are involved.
Enhancement of the Device Performance and the Stability with a Homojunction-structured Tungsten Indium Zinc Oxide Thin Film Transistor
Authors: Park Hyun-Woo , Song Aeran , Choi Dukhyun , Kim Hyung-Jun , Kwon Jang-Yeon , Chung Kwun-Bum
Published: September 2017

Tungsten-indium-zinc-oxide thin-film transistors (WIZO-TFTs) were fabricated using a radio frequency (RF) co-sputtering system with two types of source/drain (S/D)-electrode material of conducting WIZO (homojunction structure) and the indium-tin oxide (ITO) (heterojunction structure) on the same WIZO active-channel layer. The electrical properties of the WIZO layers used in the S/D electrode and the active-channel layer were adjusted through oxygen partial pressure during the deposition process. To explain enhancements of the device performance and stability of the homojunction-structured WIZO-TFT, a systematic investigation of correlation between device performance and physical properties at the interface between the active layer and the S/D electrodes such as the contact resistance, surface/interfacial roughness, interfacial-trap density, and interfacial energy-level alignments was conducted. The homojunction-structured WIZO-TFT exhibited a lower contact resistance, smaller interfacial-trap density, and flatter interfacial roughness than the WIZO-TFT with the heterojunction structure. The 0.09 eV electron barrier of the homojunction-structured WIZO-TFT is lower than the 0.21 eV value that was obtained for the heterojunction-structured WIZO-TFT. This reduced electron barrier may be attributed to enhancements of device performance and stability, that are related to the carrier transport.
Borylated oximes: versatile building blocks for organic synthesis
Authors: Liew Sean K. , Holownia Aleksandra , Diaz Diego B. , Cistrone Philip A. , Dawson Philip E. , Yudin Andrei K.
Published: September 2017

α-Boryl aldoximes – versatile synthetic intermediates that can be obtained from the corresponding α-boryl aldehydes – give rise to a range of previously inaccessible borylated products.
A series of Cd(ii) coordination polymers based on flexible bis(triazole) and multicarboxylate ligands: topological diversity, entanglement and properties
Authors: Li Ke , Blatov Vladislav A. , Fan Tao , Zheng Tian-Rui , Zhang Ya-Qian , Li Bao-Long , Wu Bing
Published: September 2017

Eight Cd(ii) coordination polymers with diverse topologies based on 1,4-bis(1,2,4-triazol-4-ylmethyl)benzene and multicarboxylate ligands were synthesized and characterized. The 3D topologies of 1, 2 and 3 are unprecedented.
Capture of volatile iodine by newly prepared and characterized non-porous [CuI]n-based coordination polymers
Authors: Tarassoli Abbas , Nobakht Valiollah , Baladi Elham , Carlucci Lucia , Proserpio Davide M.
Published: September 2017

Four new non-porous copper(i) iodide coordination polymers have been synthesized and demonstrate volatile iodine capture with simultaneous fluorescence quenching.
Developing an efficient NiCo2S4 cocatalyst for improving the visible light H2 evolution performance of CdS nanoparticles
Authors: Peng Junwen , Xu Junli , Wang Zhaoyu , Ding Zhengxin , Wang Sibo
Published: September 2017

NiCo2S4 is developed as a noble-metal-free, efficient and stable cocatalyst for improving the visible light H2 evolution performance of CdS nanoparticles.
Ion dehydration controls adsorption at the micellar interface: hydrotropic ions
Authors: Lima Filipe S. , Andrade Marcos F. C. , Mortara Laura , Gustavo Dias Luís , Cuccovia Iolanda M. , Chaimovich Hernan
Published: September 2017

The extension of ion adsorption at the micellar interface is controlled by the amount of water released from hydration shell of the ion, in the case of hydrotropic counterions.
First-principles calculations of electrical properties, structure, and phase transition of K1−xNaxNbO3 solid solutions
Authors: Yang Dong , Chai Qizhen , Wei Lingling , Chao Xiaolian , Yang Zupei
Published: September 2017

The structure, total energy and orthorhombic as well as tetragonal electronic properties of K1−xNaxNbO3 (KNN) as a function of Na concentration were studied with first principles calculations.
The electrochemical effect of various Si/Zr molar ratios on anode materials in lithium-ion batteries
Authors: Choi DongWoong , Choy KwangLeong
Published: September 2017

The aim of this study was to unveil the mechanisms of SiO2/ZrO2 (SSZ) anode materials through electrochemical analysis and to understand the effect of various Si/Zr molar ratios (Si/Zr = 0.5, 1, and 2) on the performance of SSZ anode materials with these mechanisms.
Chiral six-coordinate Dy(iii) and Tb(iii) complexes of an achiral ligand: structure, fluorescence, and magnetism
Authors: Liu Mei-Jiao , Yuan Juan , Zhang Yi-Quan , Sun Hao-Ling , Liu Cai-Ming , Kou Hui-Zhong
Published: September 2017

Two new chiral six-coordinate lanthanide complexes are obtained using an achiral ligand. Complex [Zn3Dy] displays field-induced slow magnetization relaxation, while complex [Zn3Tb] exhibits intense green photofluorescence and triboluminescence.