bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations
Authors: Diehl-Schmid Janine , Licata Abigail , Goldhardt Oliver , Förstl Hans , Yakushew Igor , Otto Markus , Anderl-Straub Sarah , Beer Ambros , Ludolph Albert Christian , Landwehrmeyer Georg Bernhard , Levin Johannes , Danek Adrian , Fliessbach Klaus , Spottke Annika , Fassbender Klaus , Lyros Epameinondas , Prudlo Johannes , Krause Bernd Joachim , Volk Alexander , Edbauer Dieter , Schroeter Matthias Leopold , Drzezga Alexander , Kornhuber Johannes , Lauer Martin ,   FTLDc Study Group, Ackl Nibal , Arnim Christine v. , Brumberg Joachim , Gärtner Florian , Jahn Holger , Kasper Elisabeth , Kassubek Jan , Prix Catharina , Riedl Lina , Roßmeier Carola , Schönecker Sonja , Semler Elisa , Teipel Stefan , Westerteicher Christine , Wlasich Elisabeth , Grimmer Timo 
Published: January 2019

AbstractC9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.
Genome-wide association study identifies a novel locus associated with psychological distress in the Japanese population
Authors: Koshimizu Hisatsugu , Nogawa Shun , Asano Shinya , Ikeda Masashi , Iwata Nakao , Takahashi Shoko , Saito Kenji , Miyakawa Tsuyoshi 
Published: January 2019

AbstractMajor depressive disorder (MDD) is a common and disabling psychiatric disorder. A recent mega analysis of genome-wide association studies (GWASs) identified 44 loci associated with MDD, though most of the genetic etiologies of the MDD/psychological distress remain unclear. To further understand the genetic basis of MDD/psychological distress, we conducted a GWAS in East Asia with more than 10,000 participants of Japanese ancestry who had enrolled in a direct-to-consumer genetic test. After quality control on the genotype data, 10,330 subjects with a total of 8,567,708 imputed SNPs were eligible for the analysis. The participants completed a self-administered questionnaire on their past medical history and health conditions that included the 6-item Kessler screening scale (K6 scale) for psychological distress (cut-off point of 5) and past medical history of MDD, resulting in 3981 subjects assigned to “psychologically distressed group” [cases], and the remaining 6349 subjects were assigned to the “non-psychologically distressed group” [controls]. In this GWAS, we found an association with genome-wide significance at rs6073833 (P = 7.60 × 10−9) in 20q13.12. This is, to the best of our knowledge, the first large-scale GWAS for psychological distress using data from direct-to-consumer (DTC) genetic tests in a population of non-European-ancestry, and the present study thus detected a novel locus significantly associated with psychological distress in the Japanese population.
Remodeling of secretory lysosomes during education tunes functional potential in NK cells
Authors: Goodridge Jodie P. , Jacobs Benedikt , Saetersmoen Michelle L. , Clement Dennis , Hammer Quirin , Clancy Trevor , Skarpen Ellen , Brech Andreas , Landskron Johannes , Grimm Christian , Pfefferle Aline , Meza-Zepeda Leonardo , Lorenz Susanne , Wiiger Merete Thune , Louch William E. , Ask Eivind Heggernes , Liu Lisa L. , Oei Vincent Yi Sheng , Kjällquist Una , Linnarsson Sten , Patel Sandip , Taskén Kjetil , Stenmark Harald , Malmberg Karl-Johan 
Published: January 2019

AbstractInhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of the acidic lysosomal compartment that mediates intracellular signalling in several cell types. Here we show that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) accumulate granzyme B in dense-core secretory lysosomes that converge close to the centrosome. This discrete morphological phenotype is independent of transcriptional programs that regulate effector function, metabolism and lysosomal biogenesis. Meanwhile, interference of signaling from acidic Ca2+ stores in primary NK cells reduces target-specific Ca2+-flux, degranulation and cytokine production. Furthermore, inhibition of PI(3,5)P2 synthesis, or genetic silencing of the PI(3,5)P2-regulated lysosomal Ca2+-channel TRPML1, leads to increased granzyme B and enhanced functional potential, thereby mimicking the educated state. These results indicate an intrinsic role for lysosomal remodeling in NK cell education.
Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury
Authors: Bellver-Landete Victor , Bretheau Floriane , Mailhot Benoit , Vallières Nicolas , Lessard Martine , Janelle Marie-Eve , Vernoux Nathalie , Tremblay Marie-Ève , Fuehrmann Tobias , Shoichet Molly S. , Lacroix Steve 
Published: January 2019

AbstractThe role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response of macrophages. Here, we use specific transgenic mouse lines and depleting agents to understand the response of microglia after SCI. We find that microglia are highly dynamic and proliferate extensively during the first two weeks, accumulating around the lesion. There, activated microglia position themselves at the interface between infiltrating leukocytes and astrocytes, which proliferate and form a scar in response to microglia-derived factors, such as IGF-1. Depletion of microglia after SCI causes disruption of glial scar formation, enhances parenchymal immune infiltrates, reduces neuronal and oligodendrocyte survival, and impairs locomotor recovery. Conversely, increased microglial proliferation, induced by local M-CSF delivery, reduces lesion size and enhances functional recovery. Altogether, our results identify microglia as a key cellular component of the scar that develops after SCI to protect neural tissue.
Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments
Authors: Lee Hong-pyo , Stowers Ryan , Chaudhuri Ovijit 
Published: January 2019

AbstractFor mesenchymal stem cells (MSCs) cultured in three dimensional matrices, matrix remodeling is associated with enhanced osteogenic differentiation. However, the mechanism linking matrix remodeling in 3D to osteogenesis of MSCs remains unclear. Here, we find that MSCs in viscoelastic hydrogels exhibit volume expansion during cell spreading, and greater volume expansion is associated with enhanced osteogenesis. Restriction of expansion by either hydrogels with slow stress relaxation or increased osmotic pressure diminishes osteogenesis, independent of cell morphology. Conversely, induced expansion by hypoosmotic pressure accelerates osteogenesis. Volume expansion is mediated by activation of TRPV4 ion channels, and reciprocal feedback between TRPV4 activation and volume expansion controls nuclear localization of RUNX2, but not YAP, to promote osteogenesis. This work demonstrates the role of cell volume in regulating cell fate in 3D culture, and identifies TRPV4 as a molecular sensor of matrix viscoelasticity that regulates osteogenic differentiation.
Simplified synthetic routes for low cost and high photovoltaic performance n-type organic semiconductor acceptors
Authors: Li Xiaojun , Pan Fei , Sun Chenkai , Zhang Ming , Wang Zhiwei , Du Jiaqi , Wang Jing , Xiao Min , Xue Lingwei , Zhang Zhi-Guo , Zhang Chunfeng , Liu Feng , Li Yongfang 
Published: January 2019

AbstractThe application of polymer solar cells (PSCs) with n-type organic semiconductor as acceptor requires further improving powder conversion efficiency, increasing stability and decreasing cost of the related materials and devices. Here we report a simplified synthetic route for 4,4,9,9-tetrahexyl-4,9-dihydro-s-indaceno [1,2-b:5,6-b’] dithiophene by using the catalyst of amberlyst15. Based on this synthetic route and methoxy substitution, two low cost acceptors with less synthetic steps, simple post-treatment and high yield were synthesized. In addition, the methoxy substitution improves both yield and efficiency. The high efficiency of 13.46% was obtained for the devices with MO-IDIC-2F (3,9-bis(2-methylene-5 or 6-fluoro-(3-(1,1-dicyanomethylene)-indanone)-4,4,9,9-tetrahexyl-5,10-dimethoxyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b’] dithiophene) as acceptor. Based on the cost analysis, the PSCs based on MO-IDIC-2F possess the great advantages of low cost and high photovoltaic performance in comparison with those PSCs reported in literatures. Therefore, MO-IDIC-2F will be a promising low cost acceptor for commercial application of PSCs.
Achieving high-fidelity single-qubit gates in a strongly driven charge qubit with 1/f charge noise
Authors: Yang Yuan-Chi , Coppersmith S. N. , Friesen Mark 
Published: January 2019

AbstractCharge qubits formed in double quantum dots represent quintessential two-level systems that enjoy both ease of control and efficient readout. Unfortunately, charge noise can cause rapid decoherence, with typical single-qubit gate fidelities falling below 90%. Here we develop analytical methods to study the evolution of strongly driven charge qubits, for general and 1/f charge-noise spectra. We show that special pulsing techniques can simultaneously suppress errors due to strong driving and charge noise, yielding single-qubit gates with fidelities above 99.9%. These results demonstrate that quantum dot charge qubits provide a potential route to high-fidelity quantum computation.
Chitosan-capped gold nanoparticles for indicating temperature abuse in frozen stored products
Authors: Mohan Chitradurga Obaiah , Gunasekaran S. , Ravishankar C. N. 
Published: January 2019

AbstractThe present study aimed to optimize the conditions for the synthesis of gold nanoparticles (AuNP) using chitosan and to assess its effectiveness as temperature threshold indication for frozen storage conditions. Chitosan concentration of 0.25% and temperature of 90 °C for 15 min was optimum for synthesizing AuNP. The maximum absorbance (λmax) was observed at 530 and 540 nm for 0.125% and 0.25% chitosan, respectively, indicating shifting of peak toward longer wavelengths (red shift) with increasing chitosan concentration indicating larger AuNPs. A prominent absorption peak at 1367 cm−1 by Fourier transform-infrared (FTIR) spectrum corresponding to C−C stretching of the glucosamine group of chitosan indicates the chitosan capping on the AuNP. Higher peak intensity and a peak shift toward shorter wavelength were observed for AuNPs exposed to frozen temperature abused conditions. Distinctly clear visible color variation from cherry red to gray indicates its application as temperature abuse indicator in frozen products.
Spatial heterogeneity of heavy metal contamination in soils and plants in Hefei, China
Authors: Zhang Qianjin , Yu Ruoyun , Fu Songling , Wu Zemin , Chen Han Y. H. , Liu Hua 
Published: January 2019

AbstractThe contamination of soil and plants with heavy metals, which has detrimental influences on plant growth, water purification, and food safety, has emerged as a serious global issue. To better understand the spatial variations of contamination of heavy metals associated city development and land use types, we collected soil samples and Magnolia grandiflora branches to quantify lead (Pb) and cadmium (Cd) contents of the roadside, industrial, residential, and park greenbelts in Hefei City, China. We found that Pb content in soil was the highest in roadside greenbelts and the lowest in parks with industrial and residential greenbelts being intermediate, while Cd in soil was the highest in greenbelts close to city center and decreased with the distance to city center. Pb in M. grandiflora, however, did not differ among greenbelt types but decreased with distance to the city center. Cd in M. grandiflora was the highest in roadside and lowest in parks and also decreased with the distance to the city center. Across all greenbelt types and the distances to the city center, Pb and Cd contents were positively correlated in soil and plants. Our findings suggest that vehicle traffic, population density, and age of urbanization collectively contribute to soil and plant contamination of Pb and Cd.
Fractional laser ablation for the targeted cutaneous delivery of an anti-CD29 monoclonal antibody – OS2966
Authors: Lapteva Maria , del Río-Sancho Sergio , Wu Eric , Carbonell W. Shawn , Böhler Christof , Kalia Yogeshvar N. 
Published: January 2019

AbstractMonoclonal antibodies targeting cytokines are administered parenterally for the systemic treatment of severe psoriasis. However, systemic exposure to the biologic increases the risk of side-effects including immunosuppression, whereas only a small fraction of the active molecules actually reaches the target organ, the skin. This preclinical study examines the feasibility of delivering a humanized anti-CD29 monoclonal antibody (OS2966) topically to skin using minimally-invasive fractional laser ablation. This approach would enable the targeted use of a biologic for the treatment of recalcitrant psoriatic plaques in patients with less widespread disease while minimizing the risk of systemic exposure. First, the effect of a wide range of laser poration conditions on skin permeation and deposition of OS2966 was tested in vitro to determine optimal microporation parameters. Subsequently, confocal laser scanning microscopy was employed to visualize the distribution of fluorescently-labelled OS2966 in skin. The results demonstrated that delivery of OS2966 into and across skin was feasible. Above fluences of 35.1 J/cm2, skin deposition and permeation were statistically superior to passive delivery reaching values up to 3.7 ± 1.2 µg/cm2 at the most aggressive condition. Selective targeting of the skin was also possible since ≥70% of the OS2966 was delivered locally to the skin. Although nanogramme quantities were able to permeate across skin, these amounts were orders of magnitude lower than levels seen following subcutaneous or intravenous injection and would result in minimal systemic exposure in vivo. The diffusion of fluorescently-labelled OS2966 into the skin surrounding the pores was clearly higher than in intact skin and demonstrated the feasibility of delivering the antibody at least as deep as the dermo-epithelial junction, a critical border region where inflammatory cells cross to promote disease progression. These preliminary results confirm that fractional laser ablation can be used for the cutaneous delivery of OS2966 and now preclinical/clinical studies are required to demonstrate therapeutic efficacy.
Craniobot: A computer numerical controlled robot for cranial microsurgeries
Authors: Ghanbari Leila , Rynes Mathew L. , Hu Jia , Schulman Daniel S. , Johnson Gregory W. , Laroque Michael , Shull Gabriella M. , Kodandaramaiah Suhasa B. 
Published: January 2019

AbstractOver the last few decades, a plethora of tools has been developed for neuroscientists to interface with the brain. Implementing these tools requires precisely removing sections of the skull to access the brain. These delicate cranial microsurgical procedures need to be performed on the sub-millimeter thick bone without damaging the underlying tissue and therefore, require significant training. Automating some of these procedures would not only enable more precise microsurgical operations, but also facilitate widespread use of advanced neurotechnologies. Here, we introduce the “Craniobot”, a cranial microsurgery platform that combines automated skull surface profiling with a computer numerical controlled (CNC) milling machine to perform a variety of cranial microsurgical procedures on mice. The Craniobot utilizes a low-force contact sensor to profile the skull surface and uses this information to perform precise milling operations within minutes. We have used the Craniobot to perform intact skull thinning and open small to large craniotomies over the dorsal cortex.
Stabilities and novel electronic structures of three carbon nitride bilayers
Authors: Lin Wanxing , Liang Shi-Dong , He Chunshan , Xie Wucheng , He Haiying , Mai Quanxiang , Li Jiesen , Yao Dao-Xin 
Published: January 2019

AbstractWe predict three novel phases of the carbon nitride (CN) bilayer, denoted α-C2N2, β-C2N2 and γ-C4N4, respectively. All of them consist of two CN sheets connected by C-C covalent bonds. The phonon dispersions reveal that all these phases are dynamically stable, because no imaginary frequency is present. The transition pathway between α-C2N2 and β-C2N2 is investigated, which involves bond-breaking and bond-reforming between C and N. This conversion is difficult, since the activation energy barrier is 1.90 eV per unit cell, high enough to prevent the transformation at room temperature. Electronic structure calculations show that all three phases are semiconductors with indirect band gaps of 3.76/5.22 eV, 4.23/5.75 eV and 2.06/3.53 eV, respectively, by PBE/HSE calculation. The β-C2N2 has the widest band gap among the three phases. All three bilayers can become metallic under tensile strain, and the indirect gap of γ-C4N4 can turn into a direct one. γ-C4N4 can become an anisotropic Dirac semimetal under uniaxial tensile strain. Anisotropic Dirac cones with high Fermi velocity of the order of 105 m/s appear under 12% strain. Our results suggest that the three two-dimensional materials have potential applications in electronics, semiconductors, optics and spintronics.
Design and assembly of a chemically switchable and fluorescently traceable light-driven proton pump system for bionanotechnological applications
Authors: Hirschi S. , Fischer N. , Kalbermatter D. , Laskowski P. R. , Ucurum Z. , Müller D. J. , Fotiadis D. 
Published: January 2019

AbstractEnergy-supplying modules are essential building blocks for the assembly of functional multicomponent nanoreactors in synthetic biology. Proteorhodopsin, a light-driven proton pump, is an ideal candidate to provide the required energy in form of an electrochemical proton gradient. Here we present an advanced proteoliposome system equipped with a chemically on-off switchable proteorhodopsin variant. The proton pump was engineered to optimize the specificity and efficiency of chemical deactivation and reactivation. To optically track and characterize the proteoliposome system using fluorescence microscopy and nanoparticle tracking analysis, fluorescenlty labelled lipids were implemented. Fluorescence is a highly valuable feature that enables detection and tracking of nanoreactors in complex media. Cryo-transmission electron microscopy, and correlative atomic force and confocal microscopy revealed that our procedure yields polylamellar proteoliposomes, which exhibit enhanced mechanical stability. The combination of these features makes the presented energizing system a promising foundation for the engineering of complex nanoreactors.
Analysis of chemical exchange saturation transfer contributions from brain metabolites to the Z-spectra at various field strengths and pH
Authors: Khlebnikov Vitaliy , van der Kemp Wybe J. M. , Hoogduin Hans , Klomp Dennis W. J. , Prompers Jeanine J. 
Published: January 2019

AbstractChemical exchange saturation transfer (CEST) exploits the chemical exchange of labile protons of an endogenous or exogenous compound with water to image the former indirectly through the water signal. Z-spectra of the brain have traditionally been analyzed for two most common saturation phenomena: downfield amide proton transfer (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body of brain metabolites, many of interest in neurology and oncology, contributes to the downfield saturation in Z-spectra. The extraction of these “hidden” metabolites from Z-spectra requires careful design of CEST sequences and data processing models, which is only possible by first obtaining CEST signatures of the brain metabolites possessing labile protons. In this work, we measured exchange rates of all major-for-CEST brain metabolites in the physiological pH range at 37 °C. Analysis of their contributions to Z-spectra revealed that regardless of the main magnetic field strength and pH, five main contributors, i.e. myo-inositol, creatine, phosphocreatine, glutamate, and mobile (poly)peptides, account for ca. 90% of downfield CEST effect. The fundamental CEST parameters presented in this study can be exploited in the design of novel CEST sequences and Z-spectra processing models, which will enable simultaneous and quantitative CEST imaging of multiple metabolites: multicolor CEST.
Optofluidic platform using liquid crystals in lithium niobate microchannel
Authors: Bonfadini Silvio , Ciciulla Fabrizio , Criante Luigino , Zaltron Annamaria , Simoni Francesco , Reshetnyak Victor , Lucchetti Liana 
Published: January 2019

AbstractWe demonstrate the all optical control of the molecular orientation of nematic liquid crystals confined in microfluidic channels engraved in lithium niobate. Microchannels are obtained by a novel approach based on femtosecond pulse laser micromachining carried on in controlled atmosphere. The combined effect of photovoltaic and pyroelectric fields generated by light in lithium niobate crystals on the liquid crystal orientation, is reported for the first time. The total space charge field and its dependence on the incident light intensity can be controlled by changing the direction of pump light propagation through the microfluidic chip. The results reported in this manuscript demonstrate that liquid crystals and lithium niobate can efficiently be combined in microfluidic configuration, in order to push forward a novel class of optofluidic devices.