bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell metastasis and invasion by targeting long non-coding RNA LOC553103
Authors: He Baoyu , Li Weiming , Wu Yingfen , Wei Fang , Gong Zhaojian , Bo Hao , Wang Yumin , Li Xiayu , Xiang Bo , Guo Can , Liao Qianjin , Chen Pan , Zu Xuyu , Zhou Ming , Ma Jian , Li Xiaoling , Li Yong , Li Guiyuan , Xiong Wei , Zeng Zhaoyang
Published: September 2016

Epstein-Barr virus (EBV) infection is causatively related to a variety of human cancers, including nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature miRNAs, a number of which have been proven to promote carcinogenesis by targeting host genes or self-viral genes. However, in this study, we found that an EBV-encoded microRNA, termed EBV-miR-BART6-3p, inhibited EBV-associated cancer cell migration and invasion including NPC and GC by reversing the epithelial–mesenchymal transition (EMT) process. Using microarray analysis, we identified and validated that a novel long non-coding RNA (lncRNA) LOC553103 was downregulated by EBV-miR-BART6-3p, and LOC553103 knockdown by specific siRNAs phenocopied the effect of EBV-miR-BART6-3p, while LOC553103 overexpression promoted cancer cell migration and invasion to facilitate EMT. In conclusion, we determined that EBV-miR-BART6-3p, a microRNA encoded by oncogenic EBV, inhibited EBV-associated cancer cell migration and invasion by targeting and downregulating a novel lncRNA LOC553103. Thus, our study presents an unreported mechanism underlying EBV infection in EBV-associated cancer carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC and other EBV-related cancers.
Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme
Authors: Günzle Jessica , Osterberg Nadja , Saavedra Joseph E , Weyerbrock Astrid
Published: September 2016

The nitric oxide (NO) donor JS-K is specifically activated by glutathione S-transferases (GSTs) in GST-overexpressing cells. We have shown the induction of cell death in glioblastoma multiforme (GBM) cells at high JS-K doses but the mechanism remains unclear. The aim of this study was to determine whether NO-induced cell death is triggered by induction of apoptotic or necrotic pathways. For the first time, we demonstrate that NO induces cell death via mitotic catastrophe (MC) with non-apoptotic mechanisms in GBM cells. Moreover, the level of morphological changes indicating MC correlates with increased necrosis. Therefore, we conclude that MC is the main mechanism by which GBM cells undergo cell death after treatment with JS-K associated with necrosis rather than apoptosis. In addition, we show that PARP1 is not an exclusive marker for late apoptosis but is also involved in MC. Activating an alternative way of cell death can be useful for the multimodal cancer therapy of GBM known for its strong anti-apoptotic mechanisms and drug resistance.
Nuclear translocation of annexin 1 following oxygen-glucose deprivation–reperfusion induces apoptosis by regulating Bid expression via p53 binding
Authors: Li Xing , Zhao Yin , Xia Qian , Zheng Lu , Liu Lu , Zhao Baoming , Shi Jing
Published: September 2016

Previous data have suggested that the nuclear translocation of annexin 1 (ANXA1) is involved in neuronal apoptosis after ischemic stroke. As the mechanism and function of ANXA1 nuclear migration remain unclear, it is important to clarify how ANXA1 performs its role as an apoptosis ‘regulator’ in the nucleus. Here we report that importazole (IPZ), an importin β (Impβ)-specific inhibitor, decreased ANXA1 nuclear accumulation and reduced the rate of neuronal death induced by nuclear ANXA1 migration after oxygen-glucose deprivation–reoxygenation (OGD/R). Notably, ANXA1 interacted with the Bid (BH3-interacting-domain death agonist) promoter directly; however; this interaction could be partially blocked by the p53 inhibitor pifithrin-α (PFT-α). Accordingly, ANXA1 was shown to interact with p53 in the nucleus and this interaction was enhanced following OGD/R. A luciferase reporter assay revealed that ANXA1 was involved in the regulation of p53-mediated transcriptional activation after OGD/R. Consistent with this finding, the nuclear translocation of ANXA1 after OGD/R upregulated the expression of Bid, which was impeded by IPZ, ANXA1 shRNA, or PFT-α. Finally, cell-survival testing demonstrated that silencing ANXA1 could improve the rate of cell survival and decrease the expression of both cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. These data suggested that Impβ-dependent nuclear ANXA1 migration participates in the OGD/R-dependent induction of neuronal apoptosis. ANXA1 interacts with p53 and promotes p53 transcriptional activity, which in turn regulates Bid expression. Silencing ANXA1 decreases the expression of Bid and suppresses caspase-3 pathway activation, thus improving cell survival after OGD/R. This study provides a novel mechanism whereby ANXA1 regulates apoptosis, suggesting the potential for a previously unidentified treatment strategy in minimizing apoptosis after OGD/R.
Black carbon absorption at the global scale is affected by particle-scale diversity in composition
Authors: Fierce Laura , Bond Tami C. , Bauer Susanne E. , Mena Francisco , Riemer Nicole
Published: September 2016

Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (Eabs) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find Eabs=1−1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.
Kinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans
Authors: Wang Yang , Zhang Yi , Chen Lianwan , Liang Qian , Yin Xiao-Ming , Miao Long , Kang Byung-Ho , Xue Ding
Published: September 2016

In most eukaryotes, mitochondria are inherited maternally. The autophagy process is critical for paternal mitochondrial elimination (PME) inCaenorhabditis elegans, but how paternal mitochondria, but not maternal mitochondria, are selectively targeted for degradation is poorly understood. Here we report that mitochondrial dynamics have a profound effect on PME. A defect in fission of paternal mitochondria delays PME, whereas a defect in fusion of paternal mitochondria accelerates PME. Surprisingly, a defect in maternal mitochondrial fusion delays PME, which is reversed by a fission defect in maternal mitochondria or by increasing maternal mitochondrial membrane potential using oligomycin. Electron microscopy and tomography analyses reveal that a proportion of maternal mitochondria are compromised when they fail to fuse normally, leading to their competition for the autophagy machinery with damaged paternal mitochondria and delayed PME. Our study indicates that mitochondrial dynamics play a critical role in regulating both the kinetics and the specificity of PME.
Bach2–Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop
Authors: Kuwahara Makoto , Ise Wataru , Ochi Mizuki , Suzuki Junpei , Kometani Kohei , Maruyama Saho , Izumoto Maya , Matsumoto Akira , Takemori Nobuaki , Takemori Ayako , Shinoda Kenta , Nakayama Toshinori , Ohara Osamu , Yasukawa Masaki , Sawasaki Tatsuya , Kurosaki Tomohiro , Yamashita Masakatsu
Published: September 2016

Although Bach2 has an important role in regulating the Th2-type immune response, the underlying molecular mechanisms remain unclear. We herein demonstrate that Bach2 associates with Batf and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2–Batf complex antagonizes the recruitment of the Batf–Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production. Furthermore, we find that Bach2 regulates the Batf and Batf3 expressions via two distinct pathways. First, Bach2 suppresses the maintenance of the Batf and Batf3 expression through the inhibition of IL-4 production. Second, the Bach2–Batf complex directly binds to the Batf and Batf3 gene loci and reduces transcription by interfering with the Batf–Irf4 complex. These findings suggest that IL-4 and Batf form a positive feedback amplification loop to induce Th2 cell differentiation and the subsequent Th2-type immune response, and Bach2–Batf interactions are required to prevent an excessive Th2 response.
Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice
Authors: Peter Saša , ten Brinke Michiel M. , Stedehouder Jeffrey , Reinelt Claudia M. , Wu Bin , Zhou Haibo , Zhou Kuikui , Boele Henk-Jan , Kushner Steven A. , Lee Min Goo , Schmeisser Michael J. , Boeckers Tobias M. , Schonewille Martijn , Hoebeek Freek E. , De Zeeuw Chris I.
Published: September 2016

Loss-of-function mutations in the gene encoding the postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology in the aetiology of ASD. Here we evaluate the possibility that cerebellar Purkinje cells (PCs) represent a critical locus of ASD-like pathophysiology in mice lacking Shank2. Absence of Shank2 impairs both PC intrinsic plasticity and induction of long-term potentiation at the parallel fibre to PC synapse. Moreover, inhibitory input onto PCs is significantly enhanced, most prominently in the posterior lobe where simple spike (SS) regularity is most affected. Using PC-specific Shank2 knockouts, we replicate alterations of SS regularity in vivo and establish cerebellar dependence of ASD-like behavioural phenotypes in motor learning and social interaction. These data highlight the importance of Shank2 for PC function, and support a model by which cerebellar pathology is prominent in certain forms of ASD.
Thermodynamics of emergent magnetic charge screening in artificial spin ice
Authors: Farhan Alan , Scholl Andreas , Petersen Charlotte F. , Anghinolfi Luca , Wuth Clemens , Dhuey Scott , Chopdekar Rajesh V. , Mellado Paula , Alava Mikko J. , van Dijken Sebastiaan
Published: September 2016

Electric charge screening is a fundamental principle governing the behaviour in a variety of systems in nature. Through reconfiguration of the local environment, the Coulomb attraction between electric charges is decreased, leading, for example, to the creation of polaron states in solids or hydration shells around proteins in water. Here, we directly visualize the real-time creation and decay of screened magnetic charge configurations in a two-dimensional artificial spin ice system, the dipolar dice lattice. By comparing the temperature dependent occurrence of screened and unscreened emergent magnetic charge defects, we determine that screened magnetic charges are indeed a result of local energy reduction and appear as a transient minimum energy state before the system relaxes towards the predicted ground state. These results highlight the important role of emergent magnetic charges in artificial spin ice, giving rise to screened charge excitations and the emergence of exotic low-temperature configurations.
Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation
Authors: Jackson-Jones Lucy H. , Duncan Sheelagh M. , Magalhaes Marlène S. , Campbell Sharon M. , Maizels Rick M. , McSorley Henry J. , Allen Judith E. , Bénézech Cécile
Published: September 2016

Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production.
Temporal asymmetries in auditory coding and perception reflect multi-layered nonlinearities
Authors: Deneux Thomas , Kempf Alexandre , Daret Aurélie , Ponsot Emmanuel , Bathellier Brice
Published: September 2016

Sound recognition relies not only on spectral cues, but also on temporal cues, as demonstrated by the profound impact of time reversals on perception of common sounds. To address the coding principles underlying such auditory asymmetries, we recorded a large sample of auditory cortex neurons using two-photon calcium imaging in awake mice, while playing sounds ramping up or down in intensity. We observed clear asymmetries in cortical population responses, including stronger cortical activity for up-ramping sounds, which matches perceptual saliency assessments in mice and previous measures in humans. Analysis of cortical activity patterns revealed that auditory cortex implements a map of spatially clustered neuronal ensembles, detecting specific combinations of spectral and intensity modulation features. Comparing different models, we show that cortical responses result from multi-layered nonlinearities, which, contrary to standard receptive field models of auditory cortex function, build divergent representations of sounds with similar spectral content, but different temporal structure.
Boron-mediated sequential alkyne insertion and C–C coupling reactions affording extended π-conjugated molecules
Authors: Shoji Yoshiaki , Tanaka Naoki , Muranaka Sho , Shigeno Naoki , Sugiyama Haruka , Takenouchi Kumiko , Hajjaj Fatin , Fukushima Takanori
Published: September 2016

C–C bond coupling reactions illustrate the wealth of organic transformations, which are usually mediated by organotransition metal complexes. Here, we show that a borafluorene with a B–Cl moiety can mediate sequential alkyne insertion (1,2-carboboration) and deborylation/Csp2–Csp2 coupling reactions, leading to aromatic molecules. The first step, which affords a borepin derivative, proceeds very efficiently between the borafluorene and various alkynes by simply mixing these two components. The second step is triggered by a one-electron oxidation of the borepin derivative, which results in the formation of a phenanthrene framework. When an excess amount of oxidant is used in the second step, the phenanthrene derivatives can be further transformed in situ to afford dibenzo[g,p]chrysene derivatives. The results presented herein will substantially expand the understanding of main group chemistry and provide a powerful synthetic tool for the construction of a wide variety of extended π-conjugated systems.
Single-domain multiferroic BiFeO3 films
Authors: Kuo C.-Y. , Hu Z. , Yang J. C. , Liao S.-C. , Huang Y. L. , Vasudevan R. K. , Okatan M. B. , Jesse S. , Kalinin S. V. , Li L. , Liu H. J. , Lai C.-H. , Pi T. W. , Agrestini S. , Chen K. , Ohresser P. , Tanaka A. , Tjeng L. H. , Chu Y. H.
Published: September 2016

The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii–Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3.
Wildlife population trends in protected areas predicted by national socio-economic metrics and body size
Authors: Barnes Megan D. , Craigie Ian D. , Harrison Luke B. , Geldmann Jonas , Collen Ben , Whitmee Sarah , Balmford Andrew , Burgess Neil D. , Brooks Thomas , Hockings Marc , Woodley Stephen
Published: September 2016

Ensuring that protected areas (PAs) maintain the biodiversity within their boundaries is fundamental in achieving global conservation goals. Despite this objective, wildlife abundance changes in PAs are patchily documented and poorly understood. Here, we use linear mixed effect models to explore correlates of population change in 1,902 populations of birds and mammals from 447 PAs globally. On an average, we find PAs are maintaining populations of monitored birds and mammals within their boundaries. Wildlife population trends are more positive in PAs located in countries with higher development scores, and for larger-bodied species. These results suggest that active management can consistently overcome disadvantages of lower reproductive rates and more severe threats experienced by larger species of birds and mammals. The link between wildlife trends and national development shows that the social and economic conditions supporting PAs are critical for the successful maintenance of their wildlife populations.
Negatively charged residues of the segment linking the enzyme and cytolysin moieties restrict the membrane-permeabilizing capacity of adenylate cyclase toxin
Authors: Masin Jiri , Osickova Adriana , Sukova Anna , Fiser Radovan , Halada Petr , Bumba Ladislav , Linhartova Irena , Osicka Radim , Sebo Peter
Published: September 2016

The whooping cough agent, Bordetella pertussis, secretes an adenylate cyclase toxin-hemolysin (CyaA) that plays a crucial role in host respiratory tract colonization. CyaA targets CR3-expressing cells and disrupts their bactericidal functions by delivering into their cytosol an adenylate cyclase enzyme that converts intracellular ATP to cAMP. In parallel, the hydrophobic domain of CyaA forms cation-selective pores that permeabilize cell membrane. The invasive AC and pore-forming domains of CyaA are linked by a segment that is unique in the RTX cytolysin family. We used mass spectrometry and circular dichroism to show that the linker segment forms α-helical structures that penetrate into lipid bilayer. Replacement of the positively charged arginine residues, proposed to be involved in target membrane destabilization by the linker segment, reduced the capacity of the toxin to translocate the AC domain across cell membrane. Substitutions of negatively charged residues then revealed that two clusters of negative charges within the linker segment control the size and the propensity of CyaA pore formation, thereby restricting the cell-permeabilizing capacity of CyaA. The ‘AC to Hly-linking segment’ thus appears to account for the smaller size and modest cell-permeabilizing capacity of CyaA pores, as compared to typical RTX hemolysins.
Quantum Transport and Nano Angle-resolved Photoemission Spectroscopy on the Topological Surface States of Single Sb2Te3 Nanowires
Authors: Arango Yulieth C. , Huang Liubing , Chen Chaoyu , Avila Jose , Asensio Maria C. , Grützmacher Detlev , Lüth Hans , Lu Jia Grace , Schäpers Thomas
Published: September 2016

We report on low-temperature transport and electronic band structure of p-type Sb2Te3 nanowires, grown by chemical vapor deposition. Magnetoresistance measurements unravel quantum interference phenomena, which depend on the cross-sectional dimensions of the nanowires. The observation of periodic Aharonov-Bohm-type oscillations is attributed to transport in topologically protected surface states in the Sb2Te3 nanowires. The study of universal conductance fluctuations demonstrates coherent transport along the Aharonov-Bohm paths encircling the rectangular cross-section of the nanowires. We use nanoscale angle-resolved photoemission spectroscopy on single nanowires (nano-ARPES) to provide direct experimental evidence on the nontrivial topological character of those surface states. The compiled study of the bandstructure and the magnetotransport response unambiguosly points out the presence of topologically protected surface states in the nanowires and their substantial contribution to the quantum transport effects, as well as the hole doping and Fermi velocity among other key issues. The results are consistent with the theoretical description of quantum transport in intrinsically doped quasi-one-dimensional topological insulator nanowires.
Distance effects in electrochemical micromachining
Authors: Xu Lizhong , Pan Yue , Zhao Chuanjun
Published: September 2016

Considering exponential dependence of currents on double-layer voltage and the feedback effect of the electrolyte resistance, a distance effect in electrochemical micromachining is found, namely that both time constant and double-layer voltage depend on the separation of electrodes. The double-layer voltage is the real voltage used in processing. Under DC voltage, the apparent voltages between two electrodes are constant for different separations, but the real voltages change with the separations. Small separations exert substantial effects on the real voltages. Accordingly, a DC-voltage small-separation electrochemical micromachining technique was proposed. The double-layer voltage drops sharply as the small separation increases. Thus, the electrochemical reactions are confined to electrode regions in very close proximity even under DC voltage. The machining precision can be significantly enhanced by reducing the voltage and separation between electrodes. With this technique, the machining of conducting materials with submicrometre precision was achieved.
Correction: Corrigendum: ACT-PRESTO: Rapid and consistent tissue clearing and labeling method for 3-dimensional (3D) imaging
Authors: Lee Eunsoo , Choi Jungyoon , Jo Youhwa , Kim Joo Yeon , Jang Yu Jin , Lee Hye Myeong , Kim So Yeun , Lee Ho-Jae , Cho Keunchang , Jung Neoncheol , Hur Eun Mi , Jeong Sung Jin , Moon Cheil , Choe Youngshik , Rhyu Im Joo , Kim Hyun , Sun Woong
Published: September 2016

Scientific Reports 6: Article number: 18631; published online: 11 January 2016; updated: 01 September 2016. In this Article and Supplementary Information file, some instances of ‘0.001M PBS’ and ‘0.01M PBS’ are incorrectly written as ‘0.01M PBS’ and ‘0.1M PBS’ respectively. With the exception of thefollowing:
Fano-like resonance emerging from magnetic and electric plasmon mode coupling in small arrays of gold particles
Authors: Bakhti Saïd , Tishchenko Alexandre V. , Zambrana-Puyalto Xavier , Bonod Nicolas , Dhuey Scott D. , Schuck P. James , Cabrini Stefano , Alayoglu Selim , Destouches Nathalie
Published: September 2016

In this work we theoretically and experimentally analyze the resonant behavior of individual 3 × 3 gold particle oligomers illuminated under normal and oblique incidence. While this structure hosts both dipolar and quadrupolar electric and magnetic delocalized modes, only dipolar electric and quadrupolar magnetic modes remain at normal incidence. These modes couple into a strongly asymmetric spectral response typical of a Fano-like resonance. In the basis of the coupled mode theory, an analytical representation of the optical extinction in terms of singular functions is used to identify the hybrid modes emerging from the electric and magnetic mode coupling and to interpret the asymmetric line profiles. Especially, we demonstrate that the characteristic Fano line shape results from the spectral interference of a broad hybrid mode with a sharp one. This structure presents a special feature in which the electric field intensity is confined on different lines of the oligomer depending on the illumination wavelength relative to the Fano dip. This Fano-type resonance is experimentally observed performing extinction cross section measurements on arrays of gold nano-disks. The vanishing of the Fano dip when increasing the incidence angle is also experimentally observed in accordance with numerical simulations.
Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial
Authors: Sadlier C. , O’Dea S. , Bennett K. , Dunne J. , Conlon N. , Bergin C.
Published: September 2016

The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22–2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15–2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals.
Evanescent Wave-Assisted Symmetry Breaking of Gold Dipolar Nanoantennas
Authors: Yang Jhen-Hong , Chen Kuo-Ping
Published: September 2016

Symmetry-breaking and scattering cancellation were observed in the dark-mode resonance of dipolar gold nanoantennas (NAs) on glass substrates coupled with oblique incidence and total internal reflection. With the assistance of evanescent waves, the coupling efficiency was twice as strong when the incidence angle was larger than the critical angle. The Hamiltonian equation and absorption spectra were used to analyze the hybridization model of symmetric dipolar gold NAs. The antibonding mode could be coupled successfully by both transverse-magnetic (TM) and transverse-electric (TE) polarizations to NAs when the dimers orientation is parallel to the propagation direction of evanescent waves.
A novel denitrifying methanotroph of the NC10 phylum and its microcolony
Authors: He Zhanfei , Cai Chaoyang , Wang Jiaqi , Xu Xinhua , Zheng Ping , Jetten Mike S. M. , Hu Baolan
Published: September 2016

The NC10 phylum is a candidate phylum of prokaryotes and is considered important in biogeochemical cycles and evolutionary history. NC10 members are as-yet-uncultured and are difficult to enrich and our knowledge regarding this phylum is largely limited to the first species ‘Candidatus Methylomirabilis oxyfera’ (M. oxyfera). Here, we enriched NC10 members from paddy soil and obtained a novel species of the NC10 phylum that mediates the anaerobic oxidation of methane (AOM) coupled to nitrite reduction. By comparing the new 16S rRNA gene sequences with those already in the database, this new species was found to be widely distributed in various habitats in China. Therefore, we tentatively named it ‘Candidatus Methylomirabilis sinica’ (M. sinica). Cells of M. sinica are roughly coccus-shaped (0.7–1.2 μm), distinct from M. oxyfera (rod-shaped; 0.25–0.5 × 0.8–1.1 μm). Notably, microscopic inspections revealed that M. sinica grew in honeycomb-shaped microcolonies, which was the first discovery of microcolony of the NC10 phylum. This finding opens the possibility to isolate NC10 members using microcolony-dependent isolation strategies.
CRISPR-Cas9 enables conditional mutagenesis of challenging loci
Authors: Schick Joel A. , Seisenberger Claudia , Beig Joachim , Bürger Antje , Iyer Vivek , Maier Viola , Perera Sajith , Rosen Barry , Skarnes William C. , Wurst Wolfgang
Published: September 2016

The International Knockout Mouse Consortium (IKMC) has produced a genome-wide collection of 15,000 isogenic targeting vectors for conditional mutagenesis in C57BL/6N mice. Although most of the vectors have been used successfully in murine embryonic stem (ES) cells, there remain a set of nearly two thousand genes that have failed to target even after several attempts. Recent attention has turned to the use of new genome editing technology for the generation of mutant alleles in mice. Here, we demonstrate how Cas9-assisted targeting can be combined with the IKMC targeting vector resource to generate conditional alleles in genes that have previously eluded targeting using conventional methods.
Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart
Authors: Sugiura Yuki , Katsumata Yoshinori , Sano Motoaki , Honda Kurara , Kajimura Mayumi , Fukuda Keiichi , Suematsu Makoto
Published: September 2016

Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered 13C6-glucose and 13C3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions.
Using spatial uncertainty to manipulate the size of the attention focus
Authors: Huang Dan , Xue Linyan , Wang Xin , Chen Yao
Published: September 2016

Preferentially processing behaviorally relevant information is vital for primate survival. In visuospatial attention studies, manipulating the spatial extent of attention focus is an important question. Although many studies have claimed to successfully adjust attention field size by either varying the uncertainty about the target location (spatial uncertainty) or adjusting the size of the cue orienting the attention focus, no systematic studies have assessed and compared the effectiveness of these methods. We used a multiple cue paradigm with 2.5° and 7.5° rings centered around a target position to measure the cue size effect, while the spatial uncertainty levels were manipulated by changing the number of cueing positions. We found that spatial uncertainty had a significant impact on reaction time during target detection, while the cue size effect was less robust. We also carefully varied the spatial scope of potential target locations within a small or large region and found that this amount of variation in spatial uncertainty can also significantly influence target detection speed. Our results indicate that adjusting spatial uncertainty is more effective than varying cue size when manipulating attention field size.
Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians
Authors: Wolfowicz Iliona , Baumgarten Sebastian , Voss Philipp A. , Hambleton Elizabeth A. , Voolstra Christian R. , Hatta Masayuki , Guse Annika
Published: September 2016

Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.
Anisotropic shrinkage of insect air sacs revealed in vivo by X-ray microtomography
Authors: Xu Liang , Chen Rongchang , Du Guohao , Yang Yiming , Wang Feixiang , Deng Biao , Xie Honglan , Xiao Tiqiao
Published: September 2016

Air sacs are thought to be the bellows for insect respiration. However, their exact mechanism of action as a bellows remains unclear. A direct way to investigate this problem is in vivo observation of the changes in their three-dimensional structures. Therefore, four-dimensional X-ray phase contrast microtomography is employed to solve this puzzle. Quantitative analysis of three-dimensional image series reveals that the compression of the air sac during respiration in bell crickets exhibits obvious anisotropic characteristics both longitudinally and transversely. Volumetric changes of the tracheal trunks in the prothorax further strengthen the evidence of this finding. As a result, we conclude that the shrinkage and expansion of the insect air sac is anisotropic, contrary to the hypothesis of isotropy, thereby providing new knowledge for further research on the insect respiratory system.
Nanostructure Formation by controlled dewetting on patterned substrates: A combined theoretical, modeling and experimental study
Authors: Lu Liang-Xing , Wang Ying-Min , Srinivasan Bharathi Madurai , Asbahi Mohamed , Yang Joel K. W. , Zhang Yong-Wei
Published: September 2016

We perform systematic two-dimensional energetic analysis to study the stability of various nanostructures formed by dewetting solid films deposited on patterned substrates. Our analytical results show that by controlling system parameters such as the substrate surface pattern, film thickness and wetting angle, a variety of equilibrium nanostructures can be obtained. Phase diagrams are presented to show the complex relations between these system parameters and various nanostructure morphologies. We further carry out both phase field simulations and dewetting experiments to validate the analytically derived phase diagrams. Good agreements between the results from our energetic analyses and those from our phase field simulations and experiments verify our analysis. Hence, the phase diagrams presented here provide guidelines for using solid-state dewetting as a tool to achieve various nanostructures.
H-aggregate analysis of P3HT thin films-Capability and limitation of photoluminescence and UV/Vis spectroscopy
Authors: Ehrenreich Philipp , Birkhold Susanne T. , Zimmermann Eugen , Hu Hao , Kim Kwang-Dae , Weickert Jonas , Pfadler Thomas , Schmidt-Mende Lukas
Published: September 2016

Polymer morphology and aggregation play an essential role for efficient charge carrier transport and charge separation in polymer-based electronic devices. It is a common method to apply the H-aggregate model to UV/Vis or photoluminescence spectra in order to analyze polymer aggregation. In this work we present strategies to obtain reliable and conclusive information on polymer aggregation and morphology based on the application of an H-aggregate analysis on UV/Vis and photoluminescence spectra. We demonstrate, with P3HT as model system, that thickness dependent reflection behavior can lead to misinterpretation of UV/Vis spectra within the H-aggregate model. Values for the exciton bandwidth can deviate by a factor of two for polymer thicknesses below 150 nm. In contrast, photoluminescence spectra are found to be a reliable basis for characterization of polymer aggregation due to their weaker dependence on the wavelength dependent refractive index of the polymer. We demonstrate this by studying the influence of surface characteristics on polymer aggregation for spin-coated thin-films that are commonly used in organic and hybrid solar cells.
A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus
Authors: DebRoy Sruti , Saldaña Miguel , Travisany Dante , Montano Andrew , Galloway-Peña Jessica , Horstmann Nicola , Yao Hui , González Mauricio , Maass Alejandro , Latorre Mauricio , Shelburne Samuel A.
Published: September 2016

Catabolite control protein A (CcpA) is a highly conserved, master regulator of carbon source utilization in gram-positive bacteria, but the CcpA regulon remains ill-defined. In this study we aimed to clarify the CcpA regulon by determining the impact of CcpA-inactivation on the virulence and transcriptome of three distinct serotypes of the major human pathogen Group AStreptococcus(GAS). CcpA-inactivation significantly decreased GAS virulence in a broad array of animal challenge models consistent with the idea that CcpA is critical to gram-positive bacterial pathogenesis. Via comparative transcriptomics, we established that the GAS CcpA core regulon is enriched for highly conserved CcpA binding motifs (i.e.cresites). Conversely, strain-specific differences in the CcpA transcriptome seems to consist primarily of affected secondary networks. Refinement ofcresite composition via analysis of the core regulon facilitated development of a modifiedcreconsensus that shows promise for improved prediction of CcpA targets in other medically relevant gram-positive pathogens.
Conversion between two conformational states of KaiC is induced by ATP hydrolysis as a trigger for cyanobacterial circadian oscillation
Authors: Oyama Katsuaki , Azai Chihiro , Nakamura Kaori , Tanaka Syun , Terauchi Kazuki
Published: September 2016

The cyanobacterial circadian oscillator can be reconstituted in vitro by mixing three clock proteins, KaiA, KaiB and KaiC, with ATP. KaiC is the only protein with circadian rhythmic activities. In the present study, we tracked the complex formation of the three Kai proteins over time using blue native (BN) polyacrylamide gel electrophoresis (PAGE), in which proteins are charged with the anionic dye Coomassie brilliant blue (CBB). KaiC was separated as three bands: the KaiABC complex, KaiC hexamer and KaiC monomer. However, no KaiC monomer was observed using gel filtration chromatography and CBB-free native PAGE. These data indicate two conformational states of KaiC hexamer and show that the ground-state KaiC (gs-KaiC) is stable and competent-state KaiC (cs-KaiC) is labile and degraded into monomers by the binding of CBB. Repeated conversions from gs-KaiC to cs-KaiC were observed over 24 h using an in vitro reconstitution system. Phosphorylation of KaiC promoted the conversion from gs-KaiC to cs-KaiC. KaiA sustained the gs-KaiC state, and KaiB bound only cs-KaiC. An E77Q/E78Q-KaiC variant that lacked N-terminal ATPase activity remained in the gs-KaiC state. Taken together, ATP hydrolysis induces the formation of cs-KaiC and promotes the binding of KaiB, which is a trigger for circadian oscillations.
Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β
Authors: Peng Yi-Jheng , Huang Jing-Jia , Wu Hao-Han , Hsieh Hsin-Ying , Wu Chia-Ying , Chen Shu-Ching , Chen Tsung-Yu , Tang Chih-Yung
Published: September 2016

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation.
Hollow Gaussian beam generation through nonlinear interaction of photons with orbital angular momentum
Authors: Chaitanya N. Apurv , Jabir M. V. , Banerji J. , Samanta G. K.
Published: September 2016

Hollow Gaussian beams (HGB) are a special class of doughnut shaped beams that do not carry orbital angular momentum (OAM). Such beams have a wide range of applications in many fields including atomic optics, bio-photonics, atmospheric science and plasma physics. Till date, these beams have been generated using linear optical elements. Here, we show a new way of generating HGBs by three-wave mixing in a nonlinear crystal. Based on nonlinear interaction of photons having OAM and conservation of OAM in nonlinear processes, we experimentally generated ultrafast HGBs of order as high as 6 and power >180 mW at 355 nm. This generic concept can be extended to any wavelength, timescales (continuous-wave and ultrafast) and any orders. We show that the removal of azimuthal phase of vortices does not produce Gaussian beam. We also propose a new and only method to characterize the order of the HGBs.
Identification of p53-target genes in Danio rerio
Authors: Mandriani Barbara , Castellana Stefano , Rinaldi Carmela , Manzoni Marta , Venuto Santina , Rodriguez-Aznar Eva , Galceran Juan , Nieto M. Angela , Borsani Giuseppe , Monti Eugenio , Mazza Tommaso , Merla Giuseppe , Micale Lucia
Published: September 2016

To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species. Although p53 functions were studied in a wide range of species, little is known about the p53-mediated transcriptional signature in Danio rerio. Here, we designed and biochemically validated a computational approach to identify novel p53 target genes in Danio rerio genome. Screening all the Danio rerio genome by pattern-matching-based analysis, we found p53 RE-like patterns proximal to 979 annotated Danio rerio genes. Prioritization analysis identified a subset of 134 candidate pattern-related genes, 31 of which have been investigated in further biochemical assays. Our study identified runx1, axin1, traf4a, hspa8, col4a5, necab2, and dnajc9 genes as novel direct p53 targets and 12 additional p53-controlled genes in Danio rerio genome. The proposed combinatorial approach resulted to be highly sensitive and robust for identifying new p53 target genes also in additional animal species.
Discovery of new diketopiperazines inhibiting Burkholderia cenocepacia quorum sensing in vitro and in vivo
Authors: Scoffone Viola C. , Chiarelli Laurent R. , Makarov Vadim , Brackman Gilles , Israyilova Aygun , Azzalin Alberto , Forneris Federico , Riabova Olga , Savina Svetlana , Coenye Tom , Riccardi Giovanna , Buroni Silvia
Published: September 2016

Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of theB. cenocepaciaacyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC50values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed goodin vivoactivity in aCaenorhabditis elegansinfection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered forin vivocombined treatments with established or novel antimicrobials, to improve the current therapeutic strategies againstB.cenocepacia.
Myostatin inhibition therapy for insulin-deficient type 1 diabetes
Authors: Coleman Samantha K. , Rebalka Irena A. , D’Souza Donna M. , Deodhare Namita , Desjardins Eric M. , Hawke Thomas J.
Published: September 2016

While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management.