bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder
Authors: Rappel Pnina , Marmor Odeya , Bick Atira S , Arkadir David , Linetsky Eduard , Castrioto Anna , Tamir Idit , Freedman Sara A. , Mevorach Tomer , Gilad Moran , Bergman Hagai , Israel Zvi , Eitan Renana 
Published: June 2018

AbstractObsessive-compulsive disorder (OCD) is a common and serious psychiatric disorder. Although subthalamic nucleus deep brain stimulation (DBS) has been studied as a treatment for OCD patients the underlying mechanism of this treatment and the optimal method of stimulation are unknown. To study the neural basis of subthalamic nucleus DBS in OCD patients we used a novel, implantable DBS system with long-term local field potential sensing capability. We focus our analysis on two patients with OCD who experienced severe treatment-resistant symptoms and were implanted with subthalamic nucleus DBS systems. We studied them for a year at rest and during provocation of OCD symptoms (46 recording sessions) and compared them to four Parkinson’s disease (PD) patients implanted with subthalamic nucleus DBS systems (69 recording sessions). We show that the dorsal (motor) area of the subthalamic nucleus in OCD patients displays a beta (25–35 Hz) oscillatory activity similar to PD patients whereas the ventral (limbic-cognitive) area of the subthalamic nucleus displays distinct theta (6.5–8 Hz) oscillatory activity only in OCD patients. The subthalamic nucleus theta oscillatory activity decreases with provocation of OCD symptoms and is inversely correlated with symptoms severity over time. We conclude that beta oscillations at the dorsal subthalamic nucleus in OCD patients challenge their pathophysiologic association with movement disorders. Furthermore, theta oscillations at the ventral subthalamic nucleus in OCD patients suggest a new physiological target for OCD therapy as well as a promising input signal for future emotional-cognitive closed-loop DBS.
The photosystem I assembly apparatus consisting of Ycf3–Y3IP1 and Ycf4 modules
Authors: Nellaepalli Sreedhar , Ozawa Shin-Ichiro , Kuroda Hiroshi , Takahashi Yuichiro 
Published: June 2018

AbstractIn oxygenic photosynthesis, light energy is converted into redox energy by two photosystems (PSI and PSII). PSI forms one of the largest multiprotein complexes in thylakoid membranes consisting of a core complex, peripheral light-harvesting complexes (LHCIs) and cofactors. Although the high-resolution structure of the PSI–LHCI complex has been determined, the assembly process remains unclear due to the rapid nature of the assembly process. Here we show that two conserved chloroplast-encoded auxiliary factors, Ycf3 and Ycf4, form modules that mediate PSI assembly. The first module consists of the tetratricopeptide repeat protein Ycf3 and its interacting partner, Y3IP1, and mainly facilitates the assembly of reaction center subunits. The second module consists of oligomeric Ycf4 and facilitates the integration of peripheral PSI subunits and LHCIs into the PSI reaction center subcomplex. We reveal that these two modules are major mediators of the PSI–LHCI assembly process.
Accelerating the discovery of insensitive high-energy-density materials by a materials genome approach
Authors: Wang Yi , Liu Yuji , Song Siwei , Yang Zhijian , Qi Xiujuan , Wang Kangcai , Liu Yu , Zhang Qinghua , Tian Yong 
Published: June 2018

AbstractFinding new high-energy-density materials with desired properties has been intensely-pursued in recent decades. However, the contradictory relationship between high energy and low mechanical sensitivity makes the innovation of insensitive high-energy-density materials an enormous challenge. Here, we show how a materials genome approach can be used to accelerate the discovery of new insensitive high-energy explosives by identification of “genetic” features, rapid molecular design, and screening, as well as experimental synthesis of a target molecule, 2,4,6-triamino-5-nitropyrimidine-1,3-dioxide. This as-synthesized energetic compound exhibits a graphite-like layered crystal structure with a high measured density of 1.95 g cm−3, high thermal decomposition temperature of 284 °C, high detonation velocity of 9169 m s−1, and extremely low mechanical sensitivities (impact sensitivity, >60 J and friction sensitivity, >360 N). Besides the considered system of six-member aromatic and hetero-aromatic rings, this materials genome approach can also be applicable to the development of new high-performing energetic materials.
Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: a pivotal interplay in the pathogenesis of Atopic Dermatitis
Authors: Di Domenico E. G. , Cavallo I. , Bordignon V. , Prignano G. , Sperduti I. , Gurtner A. , Trento E. , Toma L. , Pimpinelli F. , Capitanio B. , Ensoli F. 
Published: June 2018

AbstractIndividuals with Atopic dermatitis (AD) are highly susceptible toStaphylococcus aureuscolonization. However, the mechanisms driving this process as well as the impact ofS. aureusin AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustainingS. aureuschronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage toS. aureus. Results show that the strength of biofilm production byS. aureuscorrelated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase ofS. aureusgrowth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promoteS. aureusoutgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production byS. aureusplays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials.
Revisiting the recent European droughts from a long-term perspective
Authors: Hanel Martin , Rakovec Oldřich , Markonis Yannis , Máca Petr , Samaniego Luis , Kyselý Jan , Kumar Rohini 
Published: June 2018

AbstractEarly 21st-century droughts in Europe have been broadly regarded as exceptionally severe, substantially affecting a wide range of socio-economic sectors. These extreme events were linked mainly to increases in temperature and record-breaking heatwaves that have been influencing Europe since 2000, in combination with a lack of precipitation during the summer months. Drought propagated through all respective compartments of the hydrological cycle, involving low runoff and prolonged soil moisture deficits. What if these recent droughts are not as extreme as previously thought? Using reconstructed droughts over the last 250 years, we show that although the 2003 and 2015 droughts may be regarded as the most extreme droughts driven by precipitation deficits during the vegetation period, their spatial extent and severity at a long-term European scale are less uncommon. This conclusion is evident in our concurrent investigation of three major drought types – meteorological (precipitation), agricultural (soil moisture) and hydrological (grid-scale runoff) droughts. Additionally, unprecedented drying trends for soil moisture and corresponding increases in the frequency of agricultural droughts are also observed, reflecting the recurring periods of high temperatures. Since intense and extended meteorological droughts may reemerge in the future, our study highlights concerns regarding the impacts of such extreme events when combined with persistent decrease in European soil moisture.
Sequential Application of Discrete Topographical Patterns Enhances Derivation of Functional Mesencephalic Dopaminergic Neurons from Human Induced Pluripotent Stem Cells
Authors: Tan Kenneth K. B. , Lim Wallie Wee Meng , Chai Chou , Kukumberg Marek , Lim Kah Leong , Goh Eyleen L. K. , Yim Evelyn K. F. 
Published: June 2018

AbstractParkinson’s Disease is a progressive neurodegenerative disorder attributed to death of mesencephalic dopaminergic (DA) neurons. Pluripotent stem cells have great potential in the study for this late-onset disease, but acquirement of cells that are robust in quantity and quality is still technically demanding. Biophysical cues have been shown to direct stem cell fate, but the effect of different topographies in the lineage commitment and subsequent maturation stages of cells have been less examined. Using human induced pluripotent stem cells (iPSCs), we applied topographical patterns sequentially during differentiation stages and examined their ability to influence derivation yield and functionality of regionalized subtype-specific DA neurons. Gratings showed higher yield of DA neurons and may be beneficial for initial lineage commitment. Cells derived on pillars in the terminal differentiation stage have increased neuronal complexity, and were more capable of firing repetitive action potentials, showing that pillars yielded better network formation and functionality. Our topography platform can be applied to patient-derived iPSCs as well, and that cells harbouring LRRK2 mutation were more functionally mature when optimal topographies were applied sequentially. This will hopefully accelerate development of robust cell models that will provide novel insights into discovering new therapeutic approaches for Parkinson’s Disease.
A uniform cloning platform for mycobacterial genetics and protein production
Authors: Arnold Fabian M. , Hohl Michael , Remm Sille , Koliwer-Brandl Hendrik , Adenau Sophia , Chusri Sasitorn , Sander Peter , Hilbi Hubert , Seeger Markus A. 
Published: June 2018

AbstractMolecular research on mycobacteria relies on a multitude of tools for the genetic manipulation of these clinically important bacteria. However, a uniform set of vectors allowing for standardized cloning procedures is not available. Here, we developed a versatile series of mycobacterial vectors for gene deletion, complementation and protein production and purification. The vectors are compatible with fragment exchange (FX) cloning, a recently developed high-throughput cloning principle taking advantage of the type IIS restriction enzyme SapI and its capacity to generate sticky trinucleotide ends outside of its recognition sequence. FX cloning allows for the efficient cloning into an entry vector and the facile transfer of the sequenced insert into a variety of destination vectors. We generated a set of mycobacterial expression vectors spanning a wide range of expression strengths, tagging variants and selection markers to rapidly screen for the optimal expression construct in order to purify membrane proteins from the model organism Mycobacterium smegmatis. Further, we generated a series of suicide vectors containing two counterselection markers and used them to delete twenty genes encoding for potential drug efflux pumps in M. smegmatis. The vectors will further facilitate genetic and biochemical research on various mycobacterial species.
Localization and density of Porphyromonas gingivalis and Tannerella forsythia in gingival and subgingival granulation tissues affected by chronic or aggressive periodontitis
Authors: Rajakaruna G. Amodini , Negi Mariko , Uchida Keisuke , Sekine Masaki , Furukawa Asuka , Ito Takashi , Kobayashi Daisuke , Suzuki Yoshimi , Akashi Takumi , Umeda Makoto , Meinzer Walter , Izumi Yuichi , Eishi Yoshinobu 
Published: June 2018

AbstractPorphyromonas gingivalis and Tannerella forsythia have been thought to be associated with periodontitis; however comprehensive histopathological localization of bacteria in affected human periodontal tissues is not well documented. In the present study, we examined formalin-fixed paraffin-embedded gingival and subgingival granulation tissues from 71 patients with chronic periodontitis and 11 patients with aggressive periodontitis, using immunohistochemistry with novel monoclonal antibodies specific to P. gingivalis or T. forsythia, together with quantitative real-time polymerase chain reaction for each bacterial DNA. Immunohistochemisty revealed both bacterial species extracellularly, as aggregates or within bacterial plaque, and intracellularly in stromal inflammatory cells, squamous epithelium, and capillary endothelium of granulation tissue. Combined analysis with the results from polymerase chain reaction suggested that localization and density of T. forsythia is closely associated with those of P. gingivalis, and that bacterial density is a factor responsible for the cell-invasiveness and tissue-invasiveness of these periodontal bacteria. Detection of these bacteria in the capillary endothelium in some samples suggested possible bacterial translocation into the systemic circulation from inflamed gingival and subgingival granulation tissues. Immunohistochemistry with the novel antibodies showed high specificity and sensitivity, and can be used to locate these periodontal bacteria in routinely-used formalin-fixed paraffin-embedded human tissue sections from systemic locations.
Emissions from thaw ponds largely offset the carbon sink of northern permafrost wetlands
Authors: Kuhn McKenzie , Lundin Erik J. , Giesler Reiner , Johansson Margareta , Karlsson Jan 
Published: June 2018

AbstractNorthern regions have received considerable attention not only because the effects of climate change are amplified at high latitudes but also because this region holds vast amounts of carbon (C) stored in permafrost. These carbon stocks are vulnerable to warming temperatures and increased permafrost thaw and the breakdown and release of soil C in the form of carbon dioxide (CO2) and methane (CH4). The majority of research has focused on quantifying and upscaling the effects of thaw on CO2 and CH4 emissions from terrestrial systems. However, small ponds formed in permafrost wetlands following thawing have been recognized as hotspots for C emissions. Here, we examined the importance of small ponds for C fluxes in two permafrost wetland ecosystems in northern Sweden. Detailed flux estimates of thaw ponds during the growing season show that ponds emit, on average (±SD), 279 ± 415 and 7 ± 11 mmol C m−2 d−1 of CO2 and CH4, respectively. Importantly, addition of pond emissions to the total C budget of the wetland decreases the C sink by ~39%. Our results emphasize the need for integrated research linking C cycling on land and in water in order to make correct assessments of contemporary C balances.
A novel broad specificity fucosidase capable of core α1-6 fucose release from N-glycans labeled with urea-linked fluorescent dyes
Authors: Vainauskas Saulius , Kirk Charlotte H. , Petralia Laudine , Guthrie Ellen P. , McLeod Elizabeth , Bielik Alicia , Luebbers Alex , Foster Jeremy M. , Hokke Cornelis H. , Rudd Pauline M. , Shi Xiaofeng , Taron Christopher H. 
Published: June 2018

AbstractExoglycosidases are often used for detailed characterization of glycan structures. Bovine kidney α-fucosidase is commonly used to determine the presence of core α1-6 fucose on N-glycans, an important modification of glycoproteins. Recently, several studies have reported that removal of core α1-6-linked fucose from N-glycans labeled with the reactive N-hydroxysuccinimide carbamate fluorescent labels 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (AQC) and RapiFluor-MS is severely impeded. We report here the cloning, expression and biochemical characterization of an α-fucosidase from Omnitrophica bacterium (termed fucosidase O). We show that fucosidase O can efficiently remove α1-6- and α1-3-linked core fucose from N-glycans. Additionally, we demonstrate that fucosidase O is able to efficiently hydrolyze core α1-6-linked fucose from N-glycans labeled with any of the existing NHS-carbamate activated fluorescent dyes.
Impact of specific functional groups in flavonoids on the modulation of platelet activation
Authors: Ravishankar Divyashree , Salamah Maryam , Akimbaev Angela , Williams Harry F. , Albadawi Dina A. I. , Vaiyapuri Rajendran , Greco Francesca , Osborn Helen M. I. , Vaiyapuri Sakthivel 
Published: June 2018

AbstractFlavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
Exon Junction Complexes can have distinct functional flavours to regulate specific splicing events
Authors: Wang Zhen , Ballut Lionel , Barbosa Isabelle , Le Hir Hervé 
Published: June 2018

AbstractThe exon junction complex (EJC) deposited on spliced mRNAs, plays a central role in the post-transcriptional gene regulation and specific gene expression. The EJC core complex is associated with multiple peripheral factors involved in various post-splicing events. Here, using recombinant complex reconstitution and transcriptome-wide analysis, we showed that the EJC peripheral protein complexes ASAP and PSAP form distinct complexes with the EJC core and can confer to EJCs distinct alternative splicing regulatory activities. This study provides the first evidence that different EJCs can have distinct functions, illuminating EJC-dependent gene regulation.
The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development
Authors: Koefoed K. , Skat-Rørdam J. , Andersen P. , Warzecha C. B. , Pye M. , Andersen T. A. , Ajbro K. D. , Bendsen E. , Narimatsu M. , Vilhardt F. , Pedersen L. B. , Wrana J. L. , Anderson R. H. , Møllgård K. , Christensen S. T. , Larsen L. A. 
Published: June 2018

AbstractSmad ubiquitin regulatory factor 1 (SMURF1) is a HECT-type E3 ubiquitin ligase that plays a critical role in vertebrate development by regulating planar cell polarity (PCP) signaling and convergent extension (CE). Here we show that SMURF1 is involved in mammalian heart development. We find that SMURF1 is highly expressed in outflow tract cushion mesenchyme and Smurf1−/− mouse embryos show delayed outflow tract septation. SMURF1 is expressed in smooth muscle cells of the coronary arteries and great vessels. Thickness of the aortic smooth muscle cell layer is reduced in Smurf1−/− mouse embryos. We show that SMURF1 is a negative regulator of cardiomyogenesis and a positive regulator of smooth muscle cell and cardiac fibroblast differentiation, indicating that SMURF1 is important for cell-type specification during heart development. Finally, we provide evidence that SMURF1 localizes at the primary cilium where it may regulate bone morphogenetic protein (BMP) signaling, which controls the initial phase of cardiomyocyte differentiation. In summary, our results demonstrate that SMURF1 is a critical regulator of outflow tract septation and cell-type specification during heart development, and that these effects may in part be mediated via control of cilium-associated BMP signaling.
Cooperative light scattering from helical-phase-imprinted atomic rings
Authors: Jen H. H. , Chang M.-S. , Chen Y.-C. 
Published: June 2018

AbstractWe theoretically investigate the light scattering of super- and subradiant states of an atomic ring prepared by single excitation with a photon which carries an orbital angular momentum (OAM). For excitations with linear polarizations, the helical phase imprinted (HPI) atomic ring presents a discrete C4 rotational symmetry when number of atoms N = 4n with integers n, while for circular polarizations with arbitrary N, the continuous and C
N
symmetries emerge for the super- and subradiant modes, respectively. The HPI superradiant modes predominantly scatter photons in the forward-backward direction, and the forward scattering can be further enhanced as atomic rings are stacked along the excitation direction. The HPI subradiant modes then preferentially scatter photons in the transversal directions, and when rings are stacked concentrically and on a plane, crossover from sub- to superradiance is observed which leads to splitting and localization of the far-field scattering patterns in the polar angle. The HPI super- and subradiant states are thus detectable through measuring the far-field radiation patterns, which further allow quantum storage and detection of a single photon with an OAM.
Generation of three-dimensional optical cusp beams with ultrathin metasurfaces
Authors: Liu Weiwei , Zhang Yuchao , Gao Jie , Yang Xiaodong 
Published: June 2018

AbstractCusp beams are one type of complex structured beams with unique multiple self-accelerating channels and needle-like field structures owning great potentials to advance applications such as particle micromanipulation and super-resolution imaging. The traditional method to generate optical catastrophe is based on cumbrous reflective diffraction optical elements, which makes optical system complicated and hinders the nanophotonics integration. Here we design geometric phase based ultrathin plasmonic metasurfaces made of nanoslit antennas to produce three-dimensional (3D) optical cusp beams with variable numbers of self-accelerating channels in a broadband wavelength range. The entire beam propagation profiles of the cusp beams generated from the metasurfaces are mapped theoretically and experimentally. The special self-accelerating behavior and caustics concentration property of the cups beams are also demonstrated. Our results provide great potentials for promoting metasurface-enabled compact photonic devices used in wide applications of light-matter interactions.