bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR-Cas3 induces broad and unidirectional genome editing in human cells
Authors: Morisaka Hiroyuki , Yoshimi Kazuto , Okuzaki Yuya , Gee Peter , Kunihiro Yayoi , Sonpho Ekasit , Xu Huaigeng , Sasakawa Noriko , Naito Yuki , Nakada Shinichiro , Yamamoto Takashi , Sano Shigetoshi , Hotta Akitsu , Takeda Junji , Mashimo Tomoji 
Published: December 2019

AbstractAlthough single-component Class 2 CRISPR systems, such as type II Cas9 or type V Cas12a (Cpf1), are widely used for genome editing in eukaryotic cells, the application of multi-component Class 1 CRISPR has been less developed. Here we demonstrate that type I-E CRISPR mediates distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5′-ARG protospacer adjacent motif (PAM), without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation can be used to introduce functional gene knockouts and knock-ins. As an example of potential therapeutic applications, we show Cas3-mediated exon-skipping of the Duchenne muscular dystrophy (DMD) gene in patient-induced pluripotent stem cells (iPSCs). These findings broaden our understanding of the Class 1 CRISPR system, which may serve as a unique genome editing tool in eukaryotic cells distinct from the Class 2 CRISPR system.
Challenging immunodominance of influenza-specific CD8+ T cell responses restricted by the risk-associated HLA-A*68:01 allomorph
Authors: van de Sandt C. E. , Clemens E. B. , Grant E. J. , Rowntree L. C. , Sant S. , Halim H. , Crowe J. , Cheng A. C. , Kotsimbos T. C. , Richards M. , Miller A. , Tong S. Y. C. , Rossjohn J. , Nguyen T. H. O. , Gras S. , Chen W. , Kedzierska K. 
Published: December 2019

AbstractAlthough influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust responses. We elucidate the HLA-A*68:01+CD8+ T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145+CD8+ T cell responses. Dissecting A68/NP145+CD8+ T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145+CD8+ memory T cells with clonally expanded TCRαβs, while low-responders display A68/NP145+CD8+ T cells with predominantly naïve phenotypes and non-expanded TCRαβs. Single-cell index sorting and TCRαβ analyses link expansion of A68/NP145+CD8+ T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8+ T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8+ T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.
Multifunctional flexible membranes from sponge-like porous carbon nanofibers with high conductivity
Authors: Yan Jianhua , Dong Keqi , Zhang Yuanyuan , Wang Xiao , Aboalhassan Ahmed Abdulqawy , Yu Jianyong , Ding Bin 
Published: December 2019

AbstractConductive porous carbon nanofibers are promising for environmental, energy, and catalysis applications. However, increasing their porosity and conductivity simultaneously remains challenging. Here we report chemical crosslinking electrospinning, a macro–micro dual-phase separation method, to synthesize continuous porous carbon nanofibers with ultrahigh porosity of >80% and outstanding conductivity of 980 S cm−1. With boric acid as the crosslinking agent, poly(tetrafluoroethylene) and poly(vinyl alcohol) are crosslinked together to form water-sol webs, which are then electrospun into fibrous films. After oxidation and pyrolysis, the as-spun fibers are converted into B-F-N triply doped porous carbon nanofibers with well-controlled macro–meso–micro pores and large surface areas of ~750 m2 g−1. The sponge-like porous carbon nanofibers with substantially reduced mass transfer resistances exhibit multifunction in terms of gas adsorption, sewage disposal, liquid storage, supercapacitors, and batteries. The reported approach allows green synthesis of high-performance porous carbon nanofibers as a new platform material for numerous applications.
Programming DNA origami patterning with non-canonical DNA-based metallization reactions
Authors: Jia Sisi , Wang Jianbang , Xie Mo , Sun Jixue , Liu Huajie , Zhang Yinan , Chao Jie , Li Jiang , Wang Lihua , Lin Jianping , Gothelf Kurt V. , Fan Chunhai 
Published: December 2019

AbstractThe inherent specificity of DNA sequence hybridization has been extensively exploited to develop bioengineering applications. Nevertheless, the structural potential of DNA has been far less explored for creating non-canonical DNA-based reactions. Here we develop a DNA origami-enabled highly localized metallization reaction for intrinsic metallization patterning with 10-nm resolution. Both theoretical and experimental studies reveal that low-valence metal ions (Cu2+ and Ag+) strongly coordinate with DNA bases in protruding clustered DNA (pcDNA) prescribed on two-dimensional DNA origami, which results in effective attraction within flexible pcDNA strands for site-specific pcDNA condensation. We find that the metallization reactions occur selectively on prescribed sites while not on origami substrates. This strategy is generically applicable for free-style metal painting of alphabet letters, digits and geometric shapes on all−DNA substrates with near-unity efficiency. We have further fabricated single- and double-layer nanoscale printed circuit board (nano-PCB) mimics, shedding light on bio-inspired fabrication for nanoelectronic and nanophotonic applications.
Responses of unicellular predators to cope with the phototoxicity of photosynthetic prey
Authors: Uzuka Akihiro , Kobayashi Yusuke , Onuma Ryo , Hirooka Shunsuke , Kanesaki Yu , Yoshikawa Hirofumi , Fujiwara Takayuki , Miyagishima Shin-ya 
Published: December 2019

AbstractFeeding on unicellular photosynthetic organisms by unicellular eukaryotes is the base of the aquatic food chain and evolutionarily led to the establishment of photosynthetic endosymbionts/organelles. Photosynthesis generates reactive oxygen species and damages cells; thus, photosynthetic organisms possess several mechanisms to cope with the stress. Here, we demonstrate that photosynthetic prey also exposes unicellular amoebozoan and excavates predators to photosynthetic oxidative stress. Upon illumination, there is a commonality in transcriptomic changes among evolutionarily distant organisms feeding on photosynthetic prey. One of the genes commonly upregulated is a horizontally transferred homolog of algal and plant genes for chlorophyll degradation/detoxification. In addition, the predators reduce their phagocytic uptake while accelerating digestion of photosynthetic prey upon illumination, reducing the number of photosynthetic cells inside the predator cells, as this also occurs in facultative endosymbiotic associations upon certain stresses. Thus, some mechanisms in predators observed here probably have been necessary for evolution of endosymbiotic associations.
Tuneable reflexes control antennal positioning in flying hawkmoths
Authors: Natesan Dinesh , Saxena Nitesh , Ekeberg Örjan , Sane Sanjay P. 
Published: December 2019

AbstractComplex behaviours may be viewed as sequences of modular actions, each elicited by specific sensory cues in their characteristic timescales. From this perspective, we can construct models in which unitary behavioural modules are hierarchically placed in context of related actions. Here, we analyse antennal positioning reflex in hawkmoths as a tuneable behavioural unit. Mechanosensory feedback from two antennal structures, Böhm’s bristles (BB) and Johnston’s organs (JO), determines antennal position. At flight onset, antennae attain a specific position, which is maintained by feedback from BB. Simultaneously, JO senses deflections in flagellum-pedicel joint due to frontal airflow, to modulate its steady-state position. Restricting JO abolishes positional modulation but maintains stability against perturbations. Linear feedback models are sufficient to predict antennal dynamics at various set-points. We modelled antennal positioning as a hierarchical neural-circuit in which fast BB feedback maintains instantaneous set-point, but slow JO feedback modulates it, thereby elucidating mechanisms underlying its robustness and flexibility.
Structural order as a genuine control parameter of dynamics in simple glass formers
Authors: Tong Hua , Tanaka Hajime 
Published: December 2019

AbstractGlass transition is characterised by drastic dynamical slowing down upon cooling, accompanied by growing spatial heterogeneity. Its rationalisation by subtle changes in the liquid structure has been long debated but remains elusive, due to intrinsic difficulty in detecting the underlying complex structural ordering. Here we report that structural order parameter characterising local packing capability can well describe the glassy dynamics not only macroscopically but also microscopically, no matter whether it is driven by temperature or density. A Vogel-Fulcher-Tammann (VFT)-like relation is universally identified between the structural relaxation time and the order parameter for supercooled liquids with isotropic interactions. More importantly, we find such an intriguing VFT-like relation to be statistically valid even at a particle level, between spatially coarse-grained structural order and microscopic particle-level dynamics. Such a unified description of glassy dynamics based solely on structural order is expected to contribute to the ultimate understanding of the long-standing glass-transition problem.
Superfluid Phase Transitions and Effects of Thermal Pairing Fluctuations in Asymmetric Nuclear Matter
Authors: Tajima Hiroyuki , Hatsuda Tetsuo , van Wyk Pieter , Ohashi Yoji 
Published: December 2019

AbstractWe investigate superfluid phase transitions of asymmetric nuclear matter at finite temperature (T) and density (ρ) with a low proton fraction (Yp ≤ 0.2), which is relevant to the inner crust and outer core of neutron stars. A strong-coupling theory developed for two-component atomic Fermi gases is generalized to the four-component case, and is applied to the system of spin-1/2 neutrons and protons. The phase shifts of neutron-neutron (nn), proton-proton (pp) and neutron-proton (np) interactions up to k = 2 fm−1 are described by multi-rank separable potentials. We show that the critical temperature $${{\boldsymbol{T}}}_{{\bf{c}}}^{{\bf{n}}{\bf{n}}}$$Tcnn of the neutron superfluidity at Yp = 0 agrees well with Monte Carlo data at low densities and takes a maximum value $${{\boldsymbol{T}}}_{{\bf{c}}}^{{\bf{n}}{\bf{n}}}$$Tcnn= 1.68 MeV at $${\boldsymbol{\rho }}{\boldsymbol{/}}{{\boldsymbol{\rho }}}_{{\bf{0}}}{\boldsymbol{=}}{\bf{0.14}}$$ρ/ρ0=0.14 with ρ0 = 0.17 fm−3. Also, the critical temperature $${{\boldsymbol{T}}}_{{\bf{c}}}^{{\bf{n}}{\bf{n}}}$$Tcnn of the proton superconductivity for Yp ≤ 0.2 is substantially suppressed at low densities due to np-pairing fluctuations, and starts to dominate over $${{\boldsymbol{T}}}_{{\bf{c}}}^{{\bf{n}}{\bf{n}}}$$Tcnn only above $${\boldsymbol{\rho }}{\boldsymbol{/}}{{\boldsymbol{\rho }}}_{{\bf{0}}}{\boldsymbol{=}}{\bf{0.70}}$$ρ/ρ0=0.70(0.77) for Yp = 0.1(0.2), and (iii) the deuteron condensation temperature $${{\boldsymbol{T}}}_{{\bf{c}}}^{{\bf{d}}}$$Tcd is suppressed at Yp ≤ 0.2 due to a large mismatch of the two Fermi surfaces.
Comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies
Authors: Ali Muhammad , Kabir Firoz , Thomson Jason J. , Ma Yinghong , Qiu Caihong , Delannoy Michael , Khan Shahid Y. , Riazuddin S. Amer 
Published: December 2019

AbstractThe ocular lens serves as an excellent system to investigate the intricate details of development and differentiation. Generation of lentoid bodies or lens-like structures using pluripotent stem cells is important for understanding the processes critical for lens morphogenesis and the mechanism of cataractogenesis. We previously reported the generation of peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs). Here, we report generation of lentoid bodies from human embryonic stem cells (hESCs) and (PBMC)-originated, iPSCs employing the “fried egg” method with brief modifications. The ultrastructure analysis of hESC- and iPSC-derived lentoid bodies identified closely packed lens epithelial- and differentiating fiber-like cells. In addition, we performed RNA sequencing (RNA-Seq) based transcriptome profiling of hESC- and iPSC-derived lentoid bodies at differentiation day 25. Next-generation RNA sequencing (RNA-Seq) of hESC- and iPSC-derived lentoid bodies detected expression (≥0.659 RPKM) of 13,975 and 14,003 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies revealed 13,563 (>96%) genes common in both datasets. Among the genes common in both transcriptome datasets, 12,856 (~95%) exhibited a quantitatively similar expression profile. Next, we compared the mouse lens epithelial and fiber cell transcriptomes with hESC- and iPSC-derived lentoid bodies transcriptomes and identified > 96% overlap with lentoid body transcriptomes. In conclusion, we report first-time comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies at differentiation day 25.
Transgenerational role of seed mycobiome – an endosymbiotic fungal composition as a prerequisite to stress resilience and adaptive phenotypes in Triticum
Authors: Vujanovic Vladimir , Islam M. Nazrul , Daida Prasad 
Published: December 2019

AbstractIllumina-MiSeq next-generation sequencing of ITS 5.8S rRNA gene demonstrated the transgenerational transmission of fungal seed-endophytes (mycobiome) across three consecutive wheat host generations under standard-control and drought conditions in the greenhouse. Drought-stressed plants experienced a positive shift in the seed mycobiome’s composition, moderated by the external acquisition of endophytic Penicillium (E+) at the seed level. Untreated (E−) and unstressed plants harbor a maximal fungal diversity of non-equilibrium ecological communities. While fungal composition in drought-stressed E− plants experienced important fluctuation, E+ plants maintained fungal ecological communities in phase equilibrium across generations. E+ plants hosted a relatively higher abundance of Ascomycota in the 2nd and 3rd seed generations of wheat, whereas higher abundance of Basidiomycota was detected in 1st generation seeds. The dynamic response of ecological communities to environmental stress is conducive to E+ plants’ active recruitment of endosymbiotic consortia in seeds, benefiting host stress resilience and phenotype. In contrast, E− plants showed an erratic distribution of detected OTUs with an increased occurrence of phytopathogens and diminished plant performance under stress. The present study gives insight into the understanding of the seed-mycobiome composition and dynamics with the potential to improve plant host traits in an adverse environment.
Essential roles of autophagy in metabolic regulation in endosperm development during rice seed maturation
Authors: Sera Yuri , Hanamata Shigeru , Sakamoto Shingo , Ono Seijiro , Kaneko Kentaro , Mitsui Yuudai , Koyano Tomoko , Fujita Naoko , Sasou Ai , Masumura Takehiro , Saji Hikaru , Nonomura Ken-Ichi , Mitsuda Nobutaka , Mitsui Toshiaki , Kurusu Takamitsu , Kuchitsu Kazuyuki 
Published: December 2019

AbstractAutophagy plays crucial roles in the recycling of metabolites, and is involved in many developmental processes. Rice mutants defective in autophagy are male sterile due to immature pollens, indicating its critical role in pollen development. However, physiological roles of autophagy during seed maturation had remained unknown. We here found that seeds of the rice autophagy-deficient mutant Osatg7-1, that produces seeds at a very low frequency in paddy fields, are smaller and show chalky appearance and lower starch content in the endosperm at the mature stage under normal growth condition. We comprehensively analyzed the effects of disruption of autophagy on biochemical properties, proteome and seed quality, and found an abnormal activation of starch degradation pathways including accumulation of α-amylases in the endosperm during seed maturation in Osatg7-1. These results indicate critical involvement of autophagy in metabolic regulation in the endosperm of rice, and provide insights into novel autophagy-mediated regulation of starch metabolism during seed maturation.
Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing
Authors: Dominguez-Valentin Mev , Nakken Sigve , Tubeuf Hélène , Vodak Daniel , Ekstrøm Per Olaf , Nissen Anke M. , Morak Monika , Holinski-Feder Elke , Holth Arild , Capella Gabriel , Davidson Ben , Evans D. Gareth , Martins Alexandra , Møller Pål , Hovig Eivind 
Published: December 2019

AbstractWe have surveyed 191 prospectively sampled familial cancer patients with no previously detected pathogenic variant in the BRCA1/2, PTEN, TP53 or DNA mismatch repair genes. In all, 138 breast cancer (BC) cases, 34 colorectal cancer (CRC) and 19 multiple early-onset cancers were included. A panel of 44 cancer-predisposing genes identified 5% (9/191) pathogenic or likely pathogenic variants and 87 variants of uncertain significance (VUS). Pathogenic or likely pathogenic variants were identified mostly in familial BC individuals (7/9) and were located in 5 genes: ATM (3), BRCA2 (1), CHEK2 (1), MSH6 (1) and MUTYH (1), followed by multiple early-onset (2/9) individuals, affecting the CHEK2 and ATM genes. Eleven of the 87 VUS were tested, and 4/11 were found to have an impact on splicing by using a minigene splicing assay. We here report for the first time the splicing anomalies using this assay for the variants ATM c.3806A > G and BUB1 c.677C > T, whereas CHEK1 c.61G > A did not result in any detectable splicing anomaly. Our study confirms the presence of pathogenic or likely pathogenic variants in genes that are not routinely tested in the context of the above-mentioned clinical phenotypes. Interestingly, more than half of the pathogenic germline variants were found in the moderately penetrant ATM and CHEK2 genes, where only truncating variants from these genes are recommended to be reported in clinical genetic testing practice.
Field-induced p-n transition in yttria-stabilized zirconia
Authors: Jovaní Marc , Beltrán-Mir Héctor , Cordoncillo Eloísa , West Anthony R. 
Published: December 2019

AbstractOxide ion conducting yttria-stabilised zirconia ceramics show the onset of electronic conduction under a small bias voltage. Compositions with a high yttria content undergo a transition from p-type to n-type behavior at voltages in the range 2.4 to 10 V, which also depends on oxygen partial pressure. Surface reactions have a direct influence on bulk electronic conductivities, with possible implications for voltage-induced flash phenomena and resistive switching.
Visualization of the Stimuli-responsive Surface Behavior of Functionalized Wood Material by Chemical Force Microscopy
Authors: Gusenbauer Claudia , Cabane Etienne , Gierlinger Notburga , Colson Jérôme , Konnerth Johannes 
Published: December 2019

AbstractThe hierarchical and porous wood structure provides a stable scaffold to design functionalized lignocellulosic materials with extended properties by chemical modification techniques. However, proper nanoscale characterization methods for these novel materials are needed to confirm the presence of the added functionality and to locate the introduced functional groups with high spatial resolution. Chemical force microscopy is a suitable characterization method to distinguish chemical surface characteristics by scanning the samples surface with a functionalized tip. We report the application of this nanotechnology method on both, unmodified and functionalized wood samples to confirm the thermo-responsive behavior of poly(N-isopropylacrylamide) (PNIPAM) modified spruce wood. By performing force measurements on ultra-microtomed surfaces, adhesion force differences on the analysed structure are monitored and reveal the location and functionality of introduced functional groups. The modified samples are scanned below and above their lower critical solution temperature with a hydrophobic tip in aqueous media to observe adhesion changes. Additionally, confocal Raman microscopy support the chemical force microscopy measurements by revealing the success of the modification and the distribution of PNIPAM across the sample cross-sections. The results show that PNIPAM is mainly located in wood cell wall areas close to the lumen in early- and transitionwood.
Particle-size dependent bactericidal activity of magnesium oxide against Xanthomonas perforans and bacterial spot of tomato
Authors: Liao Y. Y. , Strayer-Scherer A. , White J. C. , De La Torre-Roche R. , Ritchie L. , Colee J. , Vallad G. E. , Freeman J. , Jones J. B. , Paret M. L. 
Published: December 2019

AbstractBacterial spot, caused by Xanthomonas spp., is a highly destructive disease of tomatoes worldwide. Copper (Cu) bactericides are often ineffective due to the presence of Cu-tolerant strains. Magnesium oxide (MgO) is an effective alternative to Cu bactericides against Xanthomonas spp. However, the effects of particle size on bactericidal activity and fruit elemental levels are unknown. In this study, nano (20 nm) and micron (0.3 and 0.6 µm) size MgO particles were compared for efficacy. Nano MgO had significantly greater in vitro bactericidal activity against Cu-tolerant X. perforans than micron MgO at 25–50 µg/ml. In field experiments nano and micron MgO applied at 200 and 1,000 µg/ml were evaluated for disease control. Nano MgO at 200 µg/ml was the only treatment that consistently reduced disease severity compared to the untreated control. Inductively Coupled Plasma Optical Emission Spectroscopy revealed that nano MgO applications did not significantly alter Mg, Cu, Ca, K, Mn, P and S accumulation compared to fruits from the untreated plots. We demonstrated that although both nano MgO and micron MgO had bactericidal activity against Cu-tolerant strains in vitro, only nano MgO was effective in bacterial spot disease management under field conditions.
Variations in tetrodotoxin levels in populations of Taricha granulosa are expressed in the morphology of their cutaneous glands
Authors: Mailho-Fontana Pedro Luiz , Jared Carlos , Antoniazzi Marta Maria , Sciani Juliana Mozer , Pimenta Daniel Carvalho , Stokes Amber N. , Grant Taran , Brodie Edmund D. , Brodie Edmund D. 
Published: December 2019

AbstractTetrodotoxin (TTX), one of the most toxic substances in nature, is present in bacteria, invertebrates, fishes, and amphibians. Marine organisms seem to bioaccumulate TTX from their food or acquire it from symbiotic bacteria, but its origin in amphibians is unclear.Taricha granulosacan exhibit high TTX levels, presumably concentrated in skin poison glands, acting as an agent of selection upon predatory garter snakes (Thamnophis). This co-evolutionary arms race induces variation inT. granulosaTTX levels, from very high to undetectable. Using morphology and biochemistry, we investigated differences in toxin localization and quality between two populations at the extremes of toxicity. TTX concentration within poison glands is related to the volume of a single cell type in which TTX occurs exclusively in distinctive secretory granules, suggesting a relationship between granule structure and chemical composition. TTX was detected in mucous glands in both populations, contradicting the general understanding that these glands do not secrete defensive chemicals and expanding currently held interpretations of amphibian skin gland functionality. Skin secretions of the two populations differed in low-mass molecules and proteins. Our results demonstrate that interpopulation variation in TTX levels is related to poison gland morphology.