bluuebunny/crossref_metadata_2025 huggingface dataset:
S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury
Authors: Kabadi Shruti V , Stoica Bogdan A , Zimmer Danna B , Afanador Lauriaselle , Duffy Kara B , Loane David J , Faden Alan I
Published: July 2015

Neuroinflammation following traumatic brain injury (TBI) is increasingly recognized to contribute to chronic tissue loss and neurologic dysfunction. Circulating levels of S100B increase after TBI and have been used as a biomarker. S100B is produced by activated astrocytes and can promote microglial activation; signaling by S100B through interaction with the multiligand advanced glycation end product-specific receptor (AGER) has been implicated in brain injury and microglial activation during chronic neurodegeneration. We examined the effects of S100B inhibition in a controlled cortical impact model, using S100B knockout mice or administration of neutralizing S100B antibody. Both interventions significantly reduced TBI-induced lesion volume, improved retention memory function, and attenuated microglial activation. The neutralizing antibody also significantly reduced sensorimotor deficits and improved neuronal survival in the cortex. However, S100B did not alter microglial activation in BV2 cells or primary microglial cultures stimulated by lipopolysaccharide or interferon gamma. Further, proximity ligation assays did not support direct interaction in the brain between S100B and AGER following TBI. Future studies are needed to elucidate specific pathways underlying S100B-mediated neuroinflammatory actions after TBI. Our results strongly implicate S100B in TBI-induced neuroinflammation, cell loss, and neurologic dysfunction, thereby indicating that it is a potential therapeutic target for TBI.
Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance
Authors: Ozmadenci Duygu , Féraud Olivier , Markossian Suzy , Kress Elsa , Ducarouge Benjamin , Gibert Benjamin , Ge Jian , Durand Isabelle , Gadot Nicolas , Plateroti Michela , Bennaceur-Griscelli Annelise , Scoazec Jean-Yves , Gil Jesus , Deng Hongkui , Bernet Agnes , Mehlen Patrick , Lavial Fabrice
Published: July 2015

The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. The use of the transcription factors Oct4, Sox2, Klf4 and c-Myc for reprogramming is extensively documented, but comparatively little is known about soluble molecules promoting reprogramming. Here we identify the secreted cue Netrin-1 and its receptor DCC, described for their respective survival/death functions in normal and oncogenic contexts, as reprogramming modulators. In various somatic cells, we found that reprogramming is accompanied by a transient transcriptional repression of Netrin-1 mediated by an Mbd3/Mta1/Chd4-containing NuRD complex. Mechanistically, Netrin-1 imbalance induces apoptosis mediated by the receptor DCC in a p53-independent manner. Correction of the Netrin-1/DCC equilibrium constrains apoptosis and improves reprogramming efficiency. Our work also sheds light on Netrin-1’s function in protecting embryonic stem cells from apoptosis mediated by its receptor UNC5b, and shows that the treatment with recombinant Netrin-1 improves the generation of mouse and human iPS cells.
Thickness dependence of the interfacial Dzyaloshinskii–Moriya interaction in inversion symmetry broken systems
Authors: Cho Jaehun , Kim Nam-Hui , Lee Sukmock , Kim June-Seo , Lavrijsen Reinoud , Solignac Aurelie , Yin Yuxiang , Han Dong-Soo , van Hoof Niels J. J. , Swagten Henk J. M. , Koopmans Bert , You Chun-Yeol
Published: July 2015

In magnetic multilayer systems, a large spin-orbit coupling at the interface between heavy metals and ferromagnets can lead to intriguing phenomena such as the perpendicular magnetic anisotropy, the spin Hall effect, the Rashba effect, and especially the interfacial Dzyaloshinskii–Moriya (IDM) interaction. This interfacial nature of the IDM interaction has been recently revisited because of its scientific and technological potential. Here we demonstrate an experimental technique to straightforwardly observe the IDM interaction, namely Brillouin light scattering. The non-reciprocal spin wave dispersions, systematically measured by Brillouin light scattering, allow not only the determination of the IDM energy densities beyond the regime of perpendicular magnetization but also the revelation of the inverse proportionality with the thickness of the magnetic layer, which is a clear signature of the interfacial nature. Altogether, our experimental and theoretical approaches involving double time Green’s function methods open up possibilities for exploring magnetic hybrid structures for engineering the IDM interaction.
Digital quantum simulation of fermionic models with a superconducting circuit
Authors: Barends R. , Lamata L. , Kelly J. , García-Álvarez L. , Fowler A. G. , Megrant A , Jeffrey E , White T. C. , Sank D. , Mutus J. Y. , Campbell B. , Chen Yu , Chen Z. , Chiaro B. , Dunsworth A. , Hoi I.-C. , Neill C. , O’Malley P. J. J. , Quintana C. , Roushan P. , Vainsencher A. , Wenner J. , Solano E. , Martinis John M.
Published: July 2015

One of the key applications of quantum information is simulating nature. Fermions are ubiquitous in nature, appearing in condensed matter systems, chemistry and high energy physics. However, universally simulating their interactions is arguably one of the largest challenges, because of the difficulties arising from anticommutativity. Here we use digital methods to construct the required arbitrary interactions, and perform quantum simulation of up to four fermionic modes with a superconducting quantum circuit. We employ in excess of 300 quantum logic gates, and reach fidelities that are consistent with a simple model of uncorrelated errors. The presented approach is in principle scalable to a larger number of modes, and arbitrary spatial dimensions.
Carbon-doped BN nanosheets for metal-free photoredox catalysis
Authors: Huang Caijin , Chen Cheng , Zhang Mingwen , Lin Lihua , Ye Xinxin , Lin Sen , Antonietti Markus , Wang Xinchen
Published: July 2015

The generation of sustainable and stable semiconductors for solar energy conversion by photoredox catalysis, for example, light-induced water splitting and carbon dioxide reduction, is a key challenge of modern materials chemistry. Here we present a simple synthesis of a ternary semiconductor, boron carbon nitride, and show that it can catalyse hydrogen or oxygen evolution from water as well as carbon dioxide reduction under visible light illumination. The ternary B–C–N alloy features a delocalized two-dimensional electron system with sp2 carbon incorporated in the h-BN lattice where the bandgap can be adjusted by the amount of incorporated carbon to produce unique functions. Such sustainable photocatalysts made of lightweight elements facilitate the innovative construction of photoredox cascades to utilize solar energy for chemical conversion.
Systematic Analysis of the Genetic Variability That Impacts SUMO Conjugation and Their Involvement in Human Diseases
Authors: Xu Hao-Dong , Shi Shao-Ping , Chen Xiang , Qiu Jian-Ding
Published: July 2015

Protein function has been observed to rely on select essential sites instead of requiring all sites to be indispensable. Small ubiquitin-related modifier (SUMO) conjugation or sumoylation, which is a highly dynamic reversible process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified, has shown to be especially valuable in cellular biology. Motivated by the significance of SUMO conjugation in biological processes, we report here on the first exploratory assessment whether sumoylation related genetic variability impacts protein functions as well as the occurrence of diseases related to SUMO. Here, we defined the SUMOAMVR as sumoylation related amino acid variations that affect sumoylation sites or enzymes involved in the process of connectivity and categorized four types of potential SUMOAMVRs. We detected that 17.13% of amino acid variations are potential SUMOAMVRs and 4.83% of disease mutations could lead to SUMOAMVR with our system. More interestingly, the statistical analysis demonstrates that the amino acid variations that directly create new potential lysine sumoylation sites are more likely to cause diseases. It can be anticipated that our method can provide more instructive guidance to identify the mechanisms of genetic diseases.
Discrimination of Transgenic Rice containing the Cry1Ab Protein using Terahertz Spectroscopy and Chemometrics
Authors: Xu Wendao , Xie Lijuan , Ye Zunzhong , Gao Weilu , Yao Yang , Chen Min , Qin Jianyuan , Ying Yibin
Published: July 2015

Spectroscopic techniques combined with chemometrics methods have proven to be effective tools for the discrimination of objects with similar properties. In this work, terahertz time-domain spectroscopy (THz-TDS) combined with discriminate analysis (DA) and principal component analysis (PCA) with derivative pretreatments was performed to differentiate transgenic rice (Hua Hui 1, containing the Cry1Ab protein) from its parent (Ming Hui 63). Both rice samples and the Cry1Ab protein were ground and pressed into pellets for terahertz (THz) measurements. The resulting time-domain spectra were transformed into frequency-domain spectra and then, the transmittances of the rice and Cry1Ab protein were calculated. By applying the first derivative of the THz spectra in conjunction with the DA model, the discrimination of transgenic from non-transgenic rice was possible with accuracies up to 89.4% and 85.0% for the calibration set and validation set, respectively. The results indicated that THz spectroscopic techniques and chemometrics methods could be new feasible ways to differentiate transgenic rice.
Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics
Authors: Zhao Chunqiu , Ur Rehman Fawad , Yang Yanlong , Li Xiaoqi , Zhang Dong , Jiang Hui , Selke Matthias , Wang Xuemei , Liu Chongyang
Published: July 2015

Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-α level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint.
High-Performance Stable Field Emission with Ultralow Turn on Voltage from rGO Conformal Coated TiO2 Nanotubes 3D Arrays
Authors: Agrawal Yogyata , Kedawat Garima , Kumar Pawan , Dwivedi Jaya , Singh V. N. , Gupta R. K. , Gupta Bipin Kumar
Published: July 2015

A facile method to produce conformal coated reduced graphene oxide (rGO) on vertically aligned titanium oxide (TiO2) nanotubes three dimensional (3D) arrays (NTAs) is demonstrated for enhanced field emission display applications. These engineered nano arrays exhibit efficient electron field emission properties such as high field emission current density (80 mA/cm2), low turn-on field (1.0 V/μm) and field enhancement factor (6000) with high emission current stability. Moreover, these enhancements observed in nano arrays attribute to the contribution of low work function with non-rectifying barriers, which allow an easy injection of electrons from the conduction band of TiO2into the Fermi level of reduced graphene oxide under external electric field. The obtained results are extremely advantageous for its potential application in field emission devices.
Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases
Authors: Hayashi Junji , Inoue Shota , Kim Kwang , Yoneda Kazunari , Kawarabayasi Yutaka , Ohshima Toshihisa , Sakuraba Haruhiko
Published: July 2015

NAD(P)-dependent dehydrogenases differ according to their coenzyme preference: some prefer NAD, others NADP and still others exhibit dual cofactor specificity. The structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for NADP. However, NADP did not act as a cofactor with this enzyme, but as a strong inhibitor of NAD-dependent homoserine oxidation. Structural analysis and site-directed mutagenesis showed that the large number of interactions between the cofactor and the enzyme are responsible for the lack of reactivity of the enzyme towards NADP. This observation suggests this enzyme exhibits a new variation on cofactor binding to a dehydrogenase: very strong NADP binding that acts as an obstacle to NAD(P)-dependent dehydrogenase catalytic activity.
Viewing Majorana Bound States by Rabi Oscillations
Authors: Wang Zhi , Liang Qi-Feng , Yao Dao-Xin , Hu Xiao
Published: July 2015

We propose to use Rabi oscillation as a probe to view the fractional Josepshon relation (FJR) associated with Majorana bound states (MBSs) expected in one-dimensional topological superconductors. The system consists of a quantum dot (QD) and an rf-SQUID with MBSs at the Josephson junction. Rabi oscillations between energy levels formed by MBSs are induced by ac gate voltage controlling the coupling between QD and MBS when the photon energy proportional to the ac frequency matches gap between quantum levels formed by MBSs and QD. As a manifestation of the Rabi oscillation in the whole system involving MBSs, the electron occupation on QD oscillates with time, which can be measured by charge sensing techniques. With Floquet theorem and numerical analysis we reveal that from the resonant driving frequency for coherent Rabi oscillation one can directly map out the FJR cos(πΦ/Φ0) as a signature of MBSs, with Φ the magnetic flux through SQUID and Φ0 = hc/2e the flux quantum. The present scheme is expected to provide a clear evidence for MBSs under intensive searching.
A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression
Authors: Korneev Sergei A. , Maconochie Mark , Naskar Souvik , Korneeva Elena I. , Richardson Guy P. , O’Shea Michael
Published: July 2015

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis.
Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency
Authors: Weng Rui , Shen Sensen , Tian Yonglu , Burton Casey , Xu Xinyuan , Liu Yi , Chang Cuilan , Bai Yu , Liu Huwei
Published: July 2015

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.
IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells
Authors: Mombelli Sarah , Cochaud Stéphanie , Merrouche Yacine , Garbar Christian , Antonicelli Frank , Laprevotte Emilie , Alberici Gilles , Bonnefoy Nathalie , Eliaou Jean-François , Bastid Jérémy , Bensussan Armand , Giustiniani Jérôme
Published: July 2015

Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we report that IL-17A and IL-17E receptors subunits mRNA expressions are upregulated in breast cancers versus normal samples. IL-17E, which is undetectable in most normal breast tissues tested, seems more expressed in some tumors. Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorogenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers.
Creep and flow of glasses: strain response linked to the spatial distribution of dynamical heterogeneities
Authors: Sentjabrskaja T. , Chaudhuri P. , Hermes M. , Poon W. C. K. , Horbach J. , Egelhaaf S. U. , Laurati M.
Published: July 2015

Mechanical properties are of central importance to materials sciences, in particular if they depend on external stimuli. Here we investigate the rheological response of amorphous solids, namely colloidal glasses, to external forces. Using confocal microscopy and computer simulations, we establish a quantitative link between the macroscopic creep response and the microscopic single-particle dynamics. We observe dynamical heterogeneities, namely regions of enhanced mobility, which remain localized in the creep regime, but grow for applied stresses leading to steady flow. These different behaviors are also reflected in the average particle dynamics, quantified by the mean squared displacement of the individual particles and the fraction of active regions. Both microscopic quantities are found to be proportional to the macroscopic strain, despite the non-equilibrium and non-linear conditions during creep and the transient regime prior to steady flow.
Cubozoan genome illuminates functional diversification of opsins and photoreceptor evolution
Authors: Liegertová Michaela , Pergner Jiří , Kozmiková Iryna , Fabian Peter , Pombinho Antonio R. , Strnad Hynek , Pačes Jan , Vlček Čestmír , Bartůněk Petr , Kozmik Zbyněk
Published: July 2015

Animals sense light primarily by an opsin-based photopigment present in a photoreceptor cell. Cnidaria are arguably the most basal phylum containing a well-developed visual system. The evolutionary history of opsins in the animal kingdom has not yet been resolved. Here, we study the evolution of animal opsins by genome-wide analysis of the cubozoan jellyfish Tripedalia cystophora, a cnidarian possessing complex lens-containing eyes and minor photoreceptors. A large number of opsin genes with distinct tissue- and stage-specific expression were identified. Our phylogenetic analysis unequivocally classifies cubozoan opsins as a sister group to c-opsins and documents lineage-specific expansion of the opsin gene repertoire in the cubozoan genome. Functional analyses provided evidence for the use of the Gs-cAMP signaling pathway in a small set of cubozoan opsins, indicating the possibility that the majority of other cubozoan opsins signal via distinct pathways. Additionally, these tests uncovered subtle differences among individual opsins, suggesting possible fine-tuning for specific photoreceptor tasks. Based on phylogenetic, expression and biochemical analysis we propose that rapid lineage- and species-specific duplications of the intron-less opsin genes and their subsequent functional diversification promoted evolution of a large repertoire of both visual and extraocular photoreceptors in cubozoans.
Increment of Access Points in Integrated System of Wavelength Division Multiplexed Passive Optical Network Radio over Fiber
Authors: Amiri I. S. , Alavi S. E. , Soltanian M. R. K. , Fisal N. , Supa’at A. S. M. , Ahmad H.
Published: July 2015

This paper describes a novel technique to increase the numbers of access points (APs) in a wavelength division multiplexed-passive optical network (WDM-PON) integrated in a 100 GHz radio-over-fiber (RoF). Eight multi-carriers separated by 25 GHz intervals were generated in the range of 193.025 to 193.200 THz using a microring resonator (MRR) system incorporating an add-drop filter system. All optically generated multi-carriers were utilized in an integrated system of WDM-PON-RoF for transmission of four 43.6 Gb/sec orthogonal frequency division multiplexing (OFDM) signals. Results showed that an acceptable BER variation for different path lengths up to 25 km was achievable for all four access points and thus the transmission of four OFDM channels is feasible for a 25 km standard single mode fiber (SSMF) path length.
Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential
Authors: Cator Lauren J. , Pietri Jose E. , Murdock Courtney C. , Ohm Johanna R. , Lewis Edwin E. , Read Andrew F. , Luckhart Shirley , Thomas Matthew B.
Published: July 2015

Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission.
Growth and reproduction of laboratory-reared neanurid Collembola using a novel slime mould diet
Authors: Hoskins Jessica L. , Janion-Scheepers Charlene , Chown Steven L. , Duffy Grant A.
Published: July 2015

Although significant progress has been made using insect taxa as model organisms, non-tracheated terrestrial arthropods, such as Collembola, are underrepresented as model species. This underrepresentation reflects the difficulty in maintaining populations of specialist Collembola species in the laboratory. Until now, no species from the family Neanuridae have been successfully reared. Here we use controlled growth experiments to provide explicit evidence that the speciesNeanura muscorumcan be raised under laboratory conditions when its diet is supplemented with slime mould. Significant gains in growth were observed in Collembola given slime mould rather than a standard diet of algae-covered bark. These benefits are further highlighted by the reproductive success of the experimental group and persistence of laboratory breeding stocks of this species and others in the family. The necessity for slime mould in the diet is attributed to the ‘suctorial’ mouthpart morphology characteristic of the Neanuridae. Maintaining laboratory populations of neanurid Collembola species will facilitate their use as model organisms, paving the way for studies that will broaden the current understanding of the environmental physiology of arthropods.
Determinants of the lethality of climate-related disasters in the Caribbean Community (CARICOM): a cross-country analysis
Authors: Andrewin Aisha N. , Rodriguez-Llanes Jose M. , Guha-Sapir Debarati
Published: July 2015

Floods and storms are climate-related hazards posing high mortality risk to Caribbean Community (CARICOM) nations. However risk factors for their lethality remain untested. We conducted an ecological study investigating risk factors for flood and storm lethality in CARICOM nations for the period 1980–2012. Lethality - deaths versus no deaths per disaster event- was the outcome. We examined biophysical and social vulnerability proxies and a decadal effect as predictors. We developed our regression model via multivariate analysis using a generalized logistic regression model with quasi-binomial distribution; removal of multi-collinear variables and backward elimination. Robustness was checked through subset analysis. We found significant positive associations between lethality, percentage of total land dedicated to agriculture (odds ratio [OR] 1.032; 95% CI: 1.013–1.053) and percentage urban population (OR 1.029, 95% CI 1.003–1.057). Deaths were more likely in the 2000–2012 period versus 1980–1989 (OR 3.708, 95% CI 1.615–8.737). Robustness checks revealed similar coefficients and directions of association. Population health in CARICOM nations is being increasingly impacted by climate-related disasters connected to increasing urbanization and land use patterns. Our findings support the evidence base for setting sustainable development goals (SDG).
Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions
Authors: Versluis Dennis , D’Andrea Marco Maria , Ramiro Garcia Javier , Leimena Milkha M. , Hugenholtz Floor , Zhang Jing , Öztürk Başak , Nylund Lotta , Sipkema Detmer , Schaik Willem van , de Vos Willem M. , Kleerebezem Michiel , Smidt Hauke , Passel Mark W.J. van
Published: July 2015

Antibiotic resistance genes are found in a broad range of ecological niches associated with complex microbiota. Here we investigated if resistance genes are not only present, but also transcribed under natural conditions. Furthermore, we examined the potential for antibiotic production by assessing the expression of associated secondary metabolite biosynthesis gene clusters. Metatranscriptome datasets from intestinal microbiota of four human adults, one human infant, 15 mice and six pigs, of which only the latter have received antibiotics prior to the study, as well as from sea bacterioplankton, a marine sponge, forest soil and sub-seafloor sediment, were investigated. We found that resistance genes are expressed in all studied ecological niches, albeit with niche-specific differences in relative expression levels and diversity of transcripts. For example, in mice and human infant microbiota predominantly tetracycline resistance genes were expressed while in human adult microbiota the spectrum of expressed genes was more diverse and also included β-lactam, aminoglycoside and macrolide resistance genes. Resistance gene expression could result from the presence of natural antibiotics in the environment, although we could not link it to expression of corresponding secondary metabolites biosynthesis clusters. Alternatively, resistance gene expression could be constitutive, or these genes serve alternative roles besides antibiotic resistance.
The Forbidden Quantum Adder
Authors: Alvarez-Rodriguez U. , Sanz M. , Lamata L. , Solano E.
Published: July 2015

Quantum information provides fundamentally different computational resources than classical information. We prove that there is no unitary protocol able to add unknown quantum states belonging to different Hilbert spaces. This is an inherent restriction of quantum physics that is related to the impossibility of copying an arbitrary quantum state, i.e., the no-cloning theorem. Moreover, we demonstrate that a quantum adder, in absence of an ancillary system, is also forbidden for a known orthonormal basis. This allows us to propose an approximate quantum adder that could be implemented in the lab. Finally, we discuss the distinct character of the forbidden quantum adder for quantum states and the allowed quantum adder for density matrices.
Proton-Detected Solid-State NMR Spectroscopy of Bone with Ultrafast Magic Angle Spinning
Authors: Mroue Kamal H. , Nishiyama Yusuke , Kumar Pandey Manoj , Gong Bo , McNerny Erin , Kohn David H. , Morris Michael D. , Ramamoorthy Ayyalusamy
Published: July 2015

While obtaining high-resolution structural details from bone is highly important to better understand its mechanical strength and the effects of aging and disease on bone ultrastructure, it has been a major challenge to do so with existing biophysical techniques. Though solid-state NMR spectroscopy has the potential to reveal the structural details of bone, it suffers from poor spectral resolution and sensitivity. Nonetheless, recent developments in magic angle spinning (MAS) NMR technology have made it possible to spin solid samples up to 110 kHz frequency. With such remarkable capabilities, 1H-detected NMR experiments that have traditionally been challenging on rigid solids can now be implemented. Here, we report the first application of multidimensional 1H-detected NMR measurements on bone under ultrafast MAS conditions to provide atomistic-level elucidation of the complex heterogeneous structure of bone. Our investigations demonstrate that two-dimensional 1H/1H chemical shift correlation spectra for bone are obtainable using fp-RFDR (finite-pulse radio-frequency-driven dipolar recoupling) pulse sequence under ultrafast MAS. Our results infer that water exhibits distinct 1H−1H dipolar coupling networks with the backbone and side-chain regions in collagen. These results show the promising potential of proton-detected ultrafast MAS NMR for monitoring structural and dynamic changes caused by mechanical loading and disease in bone.
Cyclic AMP Mimics the Anti-ageing Effects of Calorie Restriction by Up-Regulating Sirtuin
Authors: Wang Zhuoran , Zhang Lu , Liang Yaru , Zhang Chi , Xu Zhiyu , Zhang Lang , Fuji Ryosuke , Mu Wei , Li Liyuan , Jiang Junjun , Ju Yong , Wang Zhao
Published: July 2015

Cyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases.
Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation
Authors: Gualdoni Guido A. , Lingscheid Tilman , Schmetterer Klaus G. , Hennig Annika , Steinberger Peter , Zlabinger Gerhard J.
Published: July 2015

Deregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin-accumulation was examined by interference with Ca++-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1α and IL-1β secretion upon LPS stimulation. Interference with Ca++-dependent uptake abolished the cytokine-modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin’s inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF-κB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1β levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1β axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma.
A novel crosstalk between TLR4- and NOD2-mediated signaling in the regulation of intestinal inflammation
Authors: Kim Hajeong , Zhao Quanju , Zheng Hua , Li Xin , Zhang Tuo , Ma Xiaojing
Published: July 2015

Although Toll-like receptor 4 (TLR4)- and nucleotide-binding oligomerization domain 2 (NOD2)-mediated signaling mechanisms have been extensively studied individually, the crosstalk between them in the regulation of intestinal mucosal defense and tissue homeostasis has been underappreciated. Here, we uncover some novel activities of NOD2 by gene expression profiling revealing the global nature of the cross-regulation between TLR4- and NOD2-mediated signaling. Specifically, NOD2 is able to sense the intensity of TLR4-mediated signaling, resulting in either synergistic stimulation of Interluekin-12 (IL-12) production when the TLR signaling intensity is low; or in the inhibition of IL-12 synthesis and maintenance of intestinal mucosal homeostasis when the TLR signaling intensifies. This balancing act is mediated through receptor-interacting serine/threonine kinase 2 and the transcriptional regulator CCAAT/enhancer-binding protein α (C/EBPα) via its serine 248 phosphorylation by Protein Kinase C. Mice deficient in C/EBPα in the hematopoietic compartment are highly susceptible to chemically induced experimental colitis in an IL-12-dependent manner. Additionally, in contrast to the dogma, we find that the major Crohn’s disease-associated NOD2 mutations could cause a primarily immunodeficient phenotype by selectively impairing TLR4-mediated IL-12 production and host defense. To restore the impaired homeostasis would be a way forward to developing novel therapeutic strategies for inflammatory bowel diseases.
Study of Protein Expresion in Peri-Infarct Tissue after Cerebral Ischemia
Authors: Brea David , Agulla Jesús , Staes An , Gevaert Kris , Campos Francisco , Sobrino Tomás , Blanco Miguel , Dávalos Antoni , Castillo José , Ramos-Cabrer Pedro
Published: July 2015

In this work, we report our study of protein expression in rat peri-infarct tissue, 48 h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p < 0.05). Using COFRADIC, 5412 proteins were identified, with 72 showing a difference in expression. Apart from blood-related proteins (such as serum albumin), both techniques showed that the 70 kDa family of heat shock proteins were highly expressed in the peri-infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain.
Spexin Enhances Bowel Movement through Activating L-type Voltage-dependent Calcium Channel via Galanin Receptor 2 in Mice
Authors: Lin Cheng-yuan , Zhang Man , Huang Tao , Yang Li-ling , Fu Hai-bo , Zhao Ling , Zhong Linda LD , Mu Huai-xue , Shi Xiao-ke , Leung Christina FP , Fan Bao-min , Jiang Miao , Lu Ai-ping , Zhu Li-xin , Bian Zhao-xiang
Published: July 2015

A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca2+] removal and L-type voltage-dependentCa2+ channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca2+]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders.
Escherichia coli as host for membrane protein structure determination: a global analysis
Authors: Hattab Georges , Warschawski Dror E. , Moncoq Karine , Miroux Bruno
Published: July 2015

The structural biology of membrane proteins (MP) is hampered by the difficulty in producing and purifying them. A comprehensive analysis of protein databases revealed that 213 unique membrane protein structures have been obtained after production of the target protein in E. coli. The primary expression system used was the one based on the T7 RNA polymerase, followed by the arabinose and T5 promoter based expression systems. The C41λ(DE3) and C43λ(DE3) bacterial mutant hosts have contributed to 28% of non E. coli membrane protein structures. A large scale analysis of expression protocols demonstrated a preference for a combination of bacterial host-vector together with a bimodal distribution of induction temperature and of inducer concentration. Altogether our analysis provides a set of rules for the optimal use of bacterial expression systems in membrane protein production.
Field and dilution effects on the magnetic relaxation behaviours of a 1D dysprosium(iii)-carboxylate chain built from chiral ligands
Authors: Han Tian , Leng Ji-Dong , Ding You-Song , Wang Yanyan , Zheng Zhiping , Zheng Yan-Zhen
Published: July 2015

A novel enantiomer-pure dysprosium chain shows various slow magnetic relaxation behaviours depending on the field and dilution effects.
Broadscale resolving power performance of a high precision uniform field ion mobility-mass spectrometer
Authors: May Jody C. , Dodds James N. , Kurulugama Ruwan T. , Stafford George C. , Fjeldsted John C. , McLean John A.
Published: July 2015

3D surface mapping of the IM-MS instrument performance allows the maximum resolving power to be accessed for any ion system.
An impedance method for spatial sensing of 3D cell constructs – towards applications in tissue engineering
Authors: Canali C. , Mazzoni C. , Larsen L. B. , Heiskanen A. , Martinsen Ø. G. , Wolff A. , Dufva M. , Emnéus J.
Published: July 2015

We present the characterisation and validation of multiplexed 4-terminal (4T) impedance measurements as a method for sensing the spatial location of cell aggregates within large three-dimensional (3D) gelatin scaffolds.
Detection and quantification of the opioid tramadol in urine using surface enhanced Raman scattering
Authors: Alharbi Omar , Xu Yun , Goodacre Royston
Published: July 2015

SERS is developed for the quantitative detection of tramadol in artificial urine.
A sensitive LC-ESI-MS/MS method for the determination of clotrimazole in human plasma
Authors: Zhou Rui , Tang Fang , Li Sanwang , Xie Xiang , Peng Jie , Xie Feifan , Mu Lingli , Yu Peng
Published: July 2015

A systematic validation of a sensitive and rapid LC-ESI-MS/MS assay for the determination of clotrimazole in human plasma was developed for the first time.
Ultra-sensitive magnetic immunoassay of HE4 based on surface enhanced Raman spectroscopy
Authors: Ge Ming , Wei Chao , Xu Minmin , Fang Congwei , Yuan Yaxian , Gu Renao , Yao Jianlin
Published: July 2015

Human epididymis protein 4 (HE4), as a serological marker, has been proposed to be the most promising tumor marker in ovarian cancer diagnosis.
Photodimerisation of a coumarin-dipeptide gelator
Authors: Draper Emily R. , McDonald Tom O. , Adams Dave J.
Published: July 2015

Photodimerisation of a coumarin-dipeptide can be used to increase the rheological properties of the hydrogels.
An IrSi oxide film as a highly active water-oxidation catalyst in acidic media
Authors: Tran Viet-Ha , Yatabe Takeshi , Matsumoto Takahiro , Nakai Hidetaka , Suzuki Kazuharu , Enomoto Takao , Hibino Takashi , Kaneko Kenji , Ogo Seiji
Published: July 2015

We report an acid-stable IrSi oxide film made by MOCVD of an IrV complex for electrochemical water-oxidation.
Coupling cyclizations with fragmentations for the preparation of heteroaromatics: quinolines from o-alkenyl arylisocyanides and boronic acids
Authors: Evoniuk Christopher J. , Ly Michelle , Alabugin Igor V.
Published: July 2015

Stereoelectronic restrictions on homoallylic ring expansion in alkyne cascades can be overcome by using alkenes as synthetic equivalents of alkynes in reaction cascades that are terminated by C–C bond fragmentation.
Mechanical switching of magnetic interaction by tweezers-type complex
Authors: Doistau Benjamin , Cantin Jean-Louis , Chamoreau Lise-Marie , Marvaud Valérie , Hasenknopf Bernold , Vives Guillaume
Published: July 2015

An original approach using a mechanical motion to control the magnetic interaction between the two spin centers of terpy(Cu–salphen)2 complexes is presented.
Insights into collective cell behaviour from populations of coupled chemical oscillators
Authors: Taylor Annette F. , Tinsley Mark R. , Showalter Kenneth
Published: July 2015

Biological systems such as yeast show coordinated activity driven by chemical communication between cells. Experiments with coupled chemical oscillators can provide insights into the collective behaviour.
Ultraviolet-light-driven doping modulation in chemical vapor deposition grown graphene
Authors: Iqbal M. Z. , Iqbal M. W. , Khan M. F. , Eom Jonghwa
Published: July 2015

The tuning of charge carrier density of graphene is an essential factor to achieve the integration of high-efficiency electronic and optoelectronic devices.
Electron–vibration entanglement in the Born–Oppenheimer description of chemical reactions and spectroscopy
Authors: McKemmish Laura K. , McKenzie Ross H. , Hush Noel S. , Reimers Jeffrey R.
Published: July 2015

Entanglement in the diabatic basis produces useful quantum information whilst that in the adiabatic basis tells how good is the Born–Oppenheimer approximation.
Polarized emission from stretched PPV films viewed at the molecular level
Authors: Ramos Rodrigo , Siqueira Melissa F. , Cazati Thiago , Faria Roberto M. , Caldas Marilia J.
Published: July 2015

We present a study on the photoluminescence (PL) of thin films of poly-(p-phenylene vinylene) (PPV), non-stretched and uniaxially stretched.
An olive-shaped SnO2 nanocrystal-based low concentration H2S gas sensor with high sensitivity and selectivity
Authors: Hu Jun , Yin Guilin , Chen Junchen , Ge Meiying , Lu Jing , Yang Zhi , He Dannong
Published: July 2015

Olive-shaped SnO2 nanocrystals were synthesized successfully via a facile hydrothermal route, using tin dichloride hydrate, oxalic acid dihydrate and polyvinylpyrrolidone as reaction precursors, and showed great potential in the large-scale preparation of SnO2 nanocrystals.
An ultrafast spectroscopic and quantum mechanical investigation of multiple emissions in push–pull pyridinium derivatives bearing different electron donors
Authors: Carlotti B. , Benassi E. , Cesaretti A. , Fortuna C. G. , Spalletti A. , Barone V. , Elisei F.
Published: July 2015

An interconversion between rotamers in S1 was evidenced for a cationic push–pull pyrenyl derivative through a joint femtosecond fluorescence up-conversion and density functional theoretical study.
Europium, uranyl, and thorium-phenanthroline amide complexes in acetonitrile solution: an ESI-MS and DFT combined investigation
Authors: Xiao Cheng-Liang , Wang Cong-Zhi , Mei Lei , Zhang Xin-Rui , Wall Nathalie , Zhao Yu-Liang , Chai Zhi-Fang , Shi Wei-Qun
Published: July 2015

ESI-MS and density functional theory (DFT) methods were combined to elucidate the complexation mechanisms of tetradentate phenanthroline amide ligand with Eu(iii), U(vi), and Th(iv) in an acetonitrile solution.
Progress towards the validation of modeled environmental concentrations of engineered nanomaterials by analytical measurements
Authors: Nowack Bernd , Baalousha Mohamed , Bornhöft Nikolaus , Chaudhry Qasim , Cornelis Geert , Cotterill Jane , Gondikas Andreas , Hassellöv Martin , Lead Jamie , Mitrano Denise M. , von der Kammer Frank , Wontner-Smith Tim
Published: July 2015

Validation of modeled environmental concentrations of nanomaterials is currently not possible.
Free-radical conversion of a lignin model compound catalyzed by Pd/C
Authors: Fan Honglei , Yang Yingying , Song Jinliang , Meng Qinglei , Jiang Tao , Yang Guanying , Han Buxing
Published: July 2015

Benzyl phenyl ether can be decomposed into phenol and toluene effectively by using Pd/C as the catalyst in the presence of sodium carbonate and N-methyl-2-pyrrolidone via a free-radical reaction pathway.
Highly selective self-condensation of cyclic ketones using MOF-encapsulating phosphotungstic acid for renewable high-density fuel
Authors: Deng Qiang , Nie Genkuo , Pan Lun , Zou Ji-Jun , Zhang Xiangwen , Wang Li
Published: July 2015

MOF encapsulating catalyst is very selective to transfer biomass-derived cyclic ketones to mono-condensed product through self-condensation and provides great potential for the synthesis of renewable high-density biofuel.
Micromagnet arrays for on-chip focusing, switching, and separation of superparamagnetic beads and single cells
Authors: Rampini S. , Kilinc D. , Li P. , Monteil C. , Gandhi D. , Lee G. U.
Published: July 2015

We present novel micromagnet array designs for on-chip focusing, programmable transport, and size-selective sorting of superparamagnetic beads. Controlled transport of cancer cells immunolabelled with beads is provided as proof-of-concept.