bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing
Authors: Liu Zhen , Lu Zongyang , Yang Guang , Huang Shisheng , Li Guanglei , Feng Songjie , Liu Yajing , Li Jianan , Yu Wenxia , Zhang Yu , Chen Jia , Sun Qiang , Huang Xingxu 
Published: June 2018

AbstractA recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to-G base editing by using a combination of ABE and SaBE3, thus creating mouse model harboring multiple mutations. We also demonstrate the specificity of ABE by deep sequencing and whole-genome sequencing (WGS). Taken together, ABE is highly efficient and precise in vivo, making it feasible to model and potentially cure relevant genetic diseases.
Anti-phage islands force their target phage to directly mediate island excision and spread
Authors: McKitterick Amelia C. , Seed Kimberley D. 
Published: June 2018

AbstractVibrio cholerae, the causative agent of the diarrheal disease cholera, is antagonized by the lytic phage ICP1 in the aquatic environment and in human hosts. Mobile genetic elements called PLEs (phage-inducible chromosomal island-like elements) protect V. cholerae from ICP1 infection and initiate their anti-phage response by excising from the chromosome. Here, we show that PLE 1 encodes a large serine recombinase, Int, that exploits an ICP1-specific protein as a recombination directionality factor (RDF) to excise PLE 1 in response to phage infection. We show that this phage-encoded protein is sufficient to direct Int-mediated recombination in vitro and that it is highly conserved in all sequenced ICP1 genomes. Our results uncover an aspect of the molecular specificity underlying the conflict between a single predatory phage and V. cholerae PLE and contribute to our understanding of long-term evolution between phage and their bacterial hosts.
A high-quality genome sequence of Rosa chinensis to elucidate ornamental traits
Authors: Hibrand Saint-Oyant L. , Ruttink T. , Hamama L. , Kirov I. , Lakhwani D. , Zhou N. N. , Bourke P. M. , Daccord N. , Leus L. , Schulz D. , Van de Geest H. , Hesselink T. , Van Laere K. , Debray K. , Balzergue S. , Thouroude T. , Chastellier A. , Jeauffre J. , Voisine L. , Gaillard S. , Borm T. J. A. , Arens P. , Voorrips R. E. , Maliepaard C. , Neu E. , Linde M. , Le Paslier M. C. , Bérard A. , Bounon R. , Clotault J. , Choisne N. , Quesneville H. , Kawamura K. , Aubourg S. , Sakr S. , Smulders M. J. M. , Schijlen E. , Bucher E. , Debener T. , De Riek J. , Foucher F. 
Published: June 2018

AbstractRose is the world’s most important ornamental plant, with economic, cultural and symbolic value. Roses are cultivated worldwide and sold as garden roses, cut flowers and potted plants. Roses are outbred and can have various ploidy levels. Our objectives were to develop a high-quality reference genome sequence for the genus Rosa by sequencing a doubled haploid, combining long and short reads, and anchoring to a high-density genetic map, and to study the genome structure and genetic basis of major ornamental traits. We produced a doubled haploid rose line (‘HapOB’) from Rosa chinensis ‘Old Blush’ and generated a rose genome assembly anchored to seven pseudo-chromosomes (512 Mb with N50 of 3.4 Mb and 564 contigs). The length of 512 Mb represents 90.1–96.1% of the estimated haploid genome size of rose. Of the assembly, 95% is contained in only 196 contigs. The anchoring was validated using high-density diploid and tetraploid genetic maps. We delineated hallmark chromosomal features, including the pericentromeric regions, through annotation of transposable element families and positioned centromeric repeats using fluorescent in situ hybridization. The rose genome displays extensive synteny with the Fragaria vesca genome, and we delineated only two major rearrangements. Genetic diversity was analysed using resequencing data of seven diploid and one tetraploid Rosa species selected from various sections of the genus. Combining genetic and genomic approaches, we identified potential genetic regulators of key ornamental traits, including prickle density and the number of flower petals. A rose APETALA2/TOE homologue is proposed to be the major regulator of petal number in rose. This reference sequence is an important resource for studying polyploidization, meiosis and developmental processes, as we demonstrated for flower and prickle development. It will also accelerate breeding through the development of molecular markers linked to traits, the identification of the genes underlying them and the exploitation of synteny across Rosaceae.
Exploring corrections to the Optomechanical Hamiltonian
Authors: Sala Kamila , Tufarelli Tommaso 
Published: June 2018

AbstractWe compare two approaches for deriving corrections to the “linear model” of cavity optomechanics, in order to describe effects that are beyond first order in the radiation pressure coupling. In the regime where the mechanical frequency is much lower than the cavity one, we compare: (I) a widely used phenomenological Hamiltonian conserving the photon number; (II) a two-mode truncation of C. K. Law’s microscopic model, which we take as the “true” system Hamiltonian. While these approaches agree at first order, the latter model does not conserve the photon number, resulting in challenging computations. We find that approach (I) allows for several analytical predictions, and significantly outperforms the linear model in our numerical examples. Yet, we also find that the phenomenological Hamiltonian cannot fully capture all high-order corrections arising from the C. K. Law model.
Influence of the ordering of impurities on the appearance of an energy gap and on the electrical conductance of graphene
Authors: Repetsky S. P. , Vyshyvana I. G. , Kruchinin S. P. , Bellucci Stefano 
Published: June 2018

AbstractIn the one-band model of strong coupling, the influence of substitutional impurity atoms on the energy spectrum and electrical conductance of graphene is studied. It is established that the ordering of substitutional impurity atoms on nodes of the crystal lattice causes the appearance of a gap in the energy spectrum of graphene with width η|δ| centered at the point yδ, where η is the parameter of ordering, δ is the difference of the scattering potentials of impurity atoms and carbon atoms, and y is the impurity concentration. The maximum value of the parameter of ordering is $${{\boldsymbol{\eta }}}_{{\boldsymbol{\max }}}{\boldsymbol{=}}{\bf{2}}{\boldsymbol{y}}{\boldsymbol{,}}\,{\boldsymbol{y}}{\boldsymbol{\le }}{\bf{1}}/{\bf{2}}$$

η

max

=
2
y
,

y
≤
1
/
2
. For the complete ordering of impurity atoms, the energy gap width equals $${\bf{2}}{\boldsymbol{y}}{\boldsymbol{|}}{\boldsymbol{\delta }}{\boldsymbol{|}}$$
2
y

|
δ
|

. If the Fermi level falls in the region of the mentioned gap, then the electrical conductance $${{\boldsymbol{\sigma }}}_{{\boldsymbol{\alpha }}{\boldsymbol{\alpha }}}{\boldsymbol{\to }}{\bf{0}}$$

σ

α
α

→
0
at the ordering of graphene, i.e., the metal–dielectric transition arises. If the Fermi level is located outside the gap, then the electrical conductance increases with the parameter of order η by the relation $${{\boldsymbol{\sigma }}}_{{\boldsymbol{\alpha }}{\boldsymbol{\alpha }}}{\boldsymbol{ \sim }}{{\boldsymbol{(}}{{\boldsymbol{y}}}^{{\bf{2}}}{\boldsymbol{-}}\frac{{\bf{1}}}{{\bf{4}}}{{\boldsymbol{\eta }}}^{{\bf{2}}}{\boldsymbol{)}}}^{{\boldsymbol{-}}{\bf{1}}}$$

σ

α
α

~

(

y

2

−

1
4

η

2

)

−
1

. At the concentration $${\boldsymbol{y}}{\boldsymbol{=}}{\bf{1}}{\boldsymbol{/}}{\bf{2}}$$
y
=
1
/
2
, as the ordering of impurity atoms η →1, the electrical conductance of graphene $${{\boldsymbol{\sigma }}}_{{\boldsymbol{\alpha }}{\boldsymbol{\alpha }}}{\boldsymbol{\to }}{\boldsymbol{\infty }}$$

σ

α
α

→
∞
, i.e., the transition of graphene in the state of ideal electrical conductance arises.
Large trees are surrounded by more heterospecific neighboring trees in Korean pine broad-leaved natural forests
Authors: Wang Hongxiang , Peng Hui , Hui Gangying , Hu Yanbo , Zhao Zhonghua 
Published: June 2018

AbstractNegative conspecific density dependence is one of the principal mechanisms affecting plant performance and community spatial patterns. Although many studies identified the prevalence of density dependent effects in various vegetation types by analyzing conspecific spatial dispersal patterns (spatial patterning) of forest trees, interactions between individuals and heterospecific neighboring trees caused by density-dependent effects are often neglected. The effects of negative density dependence lead us to expect that neighbourhood species segregation would increase with increasing tree size and that larger trees would be surrounded by more heterospecific neighbours than would smaller trees. We studied four mapped 1-Ha plots on Changbaishan Mountain in North-eastern China and used marked point pattern analysis to explore whether trees of different sizes exhibited differences in neighbourhood species segregation; we also determined whether larger trees were more likely to have heterospecific neighbours than smaller trees were. Our results show that bigger trees generally have higher species mingling levels. Neighborhood species segregation ranged from lower than expected levels to random or nearly random patterns at small scales as tree size classes increased under heterogeneous Poisson null model tests. This study provides some evidence in support of negative density dependent effects in temperate forests.
Exposure to an anti-androgenic herbicide negatively impacts reproductive physiology and fertility in Xenopus tropicalis
Authors: Orton F. , Säfholm M. , Jansson E. , Carlsson Y. , Eriksson A. , Fick J. , Uren Webster T. , McMillan T. , Leishman M. , Verbruggen B. , Economou T. , Tyler C. R. , Berg C. 
Published: June 2018

AbstractAmphibians are threatened on a global scale and pollutants may be contributing to population declines, but how chemicals impact on their reproduction is poorly understood. We conducted a life cycle analysis to investigate the impacts of early life exposure to two anti-androgens (exposure until completion of metamorphosis;stage 66): flutamide, (50 µg/L)/linuron (9 and 45 µg/L)) on sexual development and breeding competence in Xenopus tropicalis. Our analyses included: mRNA levels of dmrt1, cyp17, amh, cyp19, foxl2 and ar (tadpoles/metamorphs), gonadal histomorphology (metamorphs/adults), mRNA levels of ar/gr (adult male brain/gonad/forelimb), testosterone/corticosterone levels (adult males), secondary sexual characteristics (forelimb width/nuptial pad: adult males) and breeding competence (amplexus/fertility: adult males). Compared to controls, feminised sex ratios and increased number of spermatogonia (adults) were observed after exposure to flutamide and the lower linuron concentration. Exposure to the lower linuron concentration also resulted in demasculinisation of secondary sexual characteristics and reduced male fertility. Flutamide exposure resulted in masculinisation of the nuptial pad and elevated mRNA levels of dmrt1, cyp17, amh and foxl2 in brains (metamorphs). Testosterone levels were higher in all treatment groups, however, overall few effects were observed in response to the higher linuron concentration. Our findings advance understanding of reproductive biology of X. tropicalis and illustrate negative effects of linuron on reproductive processes at a concentration measured in freshwater environments.
Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes
Authors: Lo Cicero Alessandra , Saidani Manoubia , Allouche Jennifer , Egesipe Anne Laure , Hoch Lucile , Bruge Celine , Sigaudy Sabine , De Sandre-Giovannoli Annachiara , Levy Nicolas , Baldeschi Christine , Nissan Xavier 
Published: June 2018

AbstractHutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that leads to premature aging. In this study, we used induced pluripotent stem cells to investigate the hypopigmentation phenotypes observed in patients with progeria. Accordingly, two iPS cell lines were derived from cells from HGPS patients and differentiated into melanocytes. Measurements of melanin content revealed a lower synthesis of melanin in HGPS melanocytes as compared to non-pathologic cells. Analysis of the melanosome maturation process by electron microscopy revealed a lower percentage of mature, fully pigmented melanosomes. Finally, a functional rescue experiment revealed the direct role of progerin in the regulation of melanogenesis. Overall, these results report a new dysregulated pathway in HGPS and open up novel perspectives in the study of pigmentation phenotypes that are associated with normal and pathological aging.
An Evolutionarily Conserved Structural Platform for PRC2 Inhibition by a Class of Ezh2 Inhibitors
Authors: Bratkowski Matthew , Yang Xin , Liu Xin 
Published: June 2018

AbstractPolycomb repressive complex 2 (PRC2) mediates trimethylation of histone H3K27 (H3K27me3), an epigenetic hallmark for repressed chromatin. Overactive mutants of the histone lysine methyltransferase subunit of PRC2, Ezh2, are found in various types of cancers. Pyridone-containing inhibitors such as GSK126 compete with S-adenosylmethionine (SAM) for Ezh2 binding and effectively inhibit PRC2 activity. PRC2 from the thermophilic fungus Chaetomium thermophilum (ct) is functionally similar to the human version in several regards and has the added advantage of producing high-resolution crystal structures, although inhibitor-bound structures of human or human/chameleon PRC2 are also available at up to 2.6 Å resolution. We solved crystal structures of both human and ctPRC2 bound to GSK126 and the structurally similar inhibitor GSK343. While the two organisms feature a disparate degree of inhibitor potency, surprisingly, GSK126 binds in a similar manner in both structures. Structure-guided protein engineering of the drug binding pocket allowed us to introduce humanizing mutations into ctEzh2 to produce a ctPRC2 variant that is more susceptible to GSK126 inhibition. Additional analysis indicated that an evolutionarily conserved structural platform dictates a unique mode of GSK126 binding, suggesting a mechanism of drug selectivity. The existing drug scaffold may thus be used to probe the function and cellular regulation of PRC2 in a wide spectrum of organisms, ranging from fungi to humans.
Quantitative Study of Abdominal Blood Flow Patterns in Patients with Aortic Dissection by 4-Dimensional Flow MRI
Authors: Liu Dongting , Fan Zhanming , Li Yu , Zhang Nan , Sun Zhonghua , An Jing , Stalder Aurélien F. , Greiser Andreas , Liu Jiayi 
Published: June 2018

AbstractThe purpose of this study is to evaluate the hemodynamic characteristics of the true lumen (TL) and the false lumen (FL) in 16 patients with aortic dissection (AD) using 4D flow magnetic resonance imaging (MRI) and thoracic and abdominal computed tomography (CT) angiography. The quantitative parameters that were measured in the TL and FL included velocity and flow. The mean area and regurgitant fraction of the TL were significantly lesser at all four levels (p < 0.05); the average through-plane velocity, peak velocity magnitude, average net flow, peak flow, and net forward volume in the TL were considerably higher (p < 0.05). The intimal entry’s size was negatively correlated with the blood flow velocity and flow rate in the TL (p < 0.05) and positively correlated with the average through-plane velocity, average net flow, and peak flow in the FL (p < 0.05); the blood flow indices in the TL were enhanced with an increase in the intimal entry numbers (p < 0.05) and the peak flow in the FL was lowered (p = 0.025); if FL thrombosis existed, the average through-plane velocity and peak velocity magnitude in the TL were substantially higher (p < 0.05). 4D flow MRI facilitates qualitative and quantitative analysis of the alterations in the abdominal aortic blood flow patterns.
A deep learning framework to discern and count microscopic nematode eggs
Authors: Akintayo Adedotun , Tylka Gregory L. , Singh Asheesh K. , Ganapathysubramanian Baskar , Singh Arti , Sarkar Soumik 
Published: June 2018

AbstractIn order to identify and control the menace of destructive pests via microscopic image-based identification state-of-the art deep learning architecture is demonstrated on the parasitic worm, the soybean cyst nematode (SCN), Heterodera glycines. Soybean yield loss is negatively correlated with the density of SCN eggs that are present in the soil. While there has been progress in automating extraction of egg-filled cysts and eggs from soil samples counting SCN eggs obtained from soil samples using computer vision techniques has proven to be an extremely difficult challenge. Here we show that a deep learning architecture developed for rare object identification in clutter-filled images can identify and count the SCN eggs. The architecture is trained with expert-labeled data to effectively build a machine learning model for quantifying SCN eggs via microscopic image analysis. We show dramatic improvements in the quantification time of eggs while maintaining human-level accuracy and avoiding inter-rater and intra-rater variabilities. The nematode eggs are correctly identified even in complex, debris-filled images that are often difficult for experts to identify quickly. Our results illustrate the remarkable promise of applying deep learning approaches to phenotyping for pest assessment and management.
Temporal and spectral EEG dynamics can be indicators of stealth placement
Authors: Wang Regina W. Y. , Chen Yi-Chung , Liu I-Ning , Chuang Shang-Wen 
Published: June 2018

AbstractStealth placement marketing, where consumers are unaware that they are being marketed to, attempts to reduce the audiences’ resistance to traditional persuasive advertising. It is a form of advertising that involves targeted exposure of brands or products incorporated in other works, usually with or without explicit reference to the brands or products. Brand placement can be presented in different visual and auditory forms in video programs. The present study proposed that different ‘representations’ (i.e., representable or non-representable) and ‘sounds’ (i.e., speech or musical sound) of brand placement can affect the viewers’ perception of the brand. Event-related potential results indicated significant differences in P1, N1, P2, N270, and P3. Further, event-related spectral perturbation results indicated significant differences in theta, alpha, beta, and gamma (30–100 Hz), in the right parietal, right occipital area, and limbic lobe. ‘Non-representable’ or ‘speech sound’ brand placement induced significant temporal and spectral EEG dynamics in viewers.
Thermodynamics of CuPt nanoalloys
Authors: Rossi K. , Pártay L. B. , Csányi G. , Baletto F. 
Published: June 2018

AbstractThe control of structural and chemical transitions in bimetallic nanoalloys at finite temperatures is one of the challenges for their use in advanced applications. Comparing Nested Sampling and Molecular Dynamics simulations, we investigate the phase changes of CuPt nanoalloys with the aim to elucidate the role of kinetic effects during their solidification and melting processes. We find that the quasi-thermodynamic limit for the nucleation of (CuPt)309 is 965 ± 10 K, but its prediction is increasingly underestimated when the system is cooled faster than 109 K/s. The solidified nanoparticles, classified following a novel tool based on Steinhardt parameters and the relative orientation of characteristic atomic environments, are then heated back to their liquid phase. We demonstrate the kinetic origin of the hysteresis in the caloric curve as (i) it closes for rates slower than 108 K/s, with a phase change temperature of 970 K ± 25 K, in very good agreement with its quasi-thermodynamic limit; (ii) the process happens simultaneously in the inner and outer layers; (iii) an onion-shell chemical order - Cu-rich surface, Pt-rich sub-surface, and mixed core - is always preserved.
An ex vivo salivary lubrication system to mimic xerostomic conditions and to predict the lubricating properties of xerostomia relieving agents
Authors: Vinke Jeroen , Kaper Hans J. , Vissink Arjan , Sharma Prashant K. 
Published: June 2018

AbstractAdvances in medical research has resulted in successful treatment of many life-threatening infectious diseases as well as autoimmune and lifestyle-related diseases, increasing life-expectancy of both the developed and developing world. As a result of a growing ageing population, the focus has also turned on chronic diseases which seriously affect the quality of older patient life. Xerostomia (dry mouth) is one such condition, which leads to bad oral health and difficulty in consumption of dry foods and speech. Saliva substitutes are used to ease symptoms. However, they often don’t work properly and objective comparison of saliva substitutes to mimic natural salivary functions does not exist. The study thus aims to develop an ex vivo friction assay simulating dry mouth conditions and facilitating objective comparison of saliva substitutes. A reciprocating sliding tongue-enamel system was developed and compared to a PDMS (polydimethylsiloxane)-PDMS friction system. The tongue-enamel system, but not the PDMS-PDMS model, showed high mucin-containing saliva (unstimulated and submandibular/sublingual saliva) to give higher Relief than mucin-poor lubricants (water, parotid saliva, Dentaid Xeros) and correlated well (r = 0.97) with in vivo mouth feel. The tongue-enamel friction system mimicked dry mouth conditions and relief and seems suited to test agents meant to lubricate desiccated oral surfaces.
Oxidation of squalene by singlet oxygen and free radicals results in different compositions of squalene monohydroperoxide isomers
Authors: Shimizu Naoki , Ito Junya , Kato Shunji , Otoki Yurika , Goto Masashi , Eitsuka Takahiro , Miyazawa Teruo , Nakagawa Kiyotaka 
Published: June 2018

AbstractOxidation of squalene (SQ) causes a decline in the nutritional value of SQ in foods, as well as an accumulation of SQ oxidation products in skin lipids which lead to adverse skin conditions. However, mechanistic insights as to how SQ is oxidized by different oxidation mechanisms have been limited, and thus effective measures towards the prevention of SQ oxidation have not been identified. In this study, we oxidized SQ by either singlet oxygen oxidation or free radical oxidation, and monitored the formation of the six SQ monohydroperoxide (SQOOH) isomers, the primary oxidation products of SQ, at the isomeric level. While singlet oxygen oxidation of SQ resulted in the formation of similar amounts of the six SQOOH isomers, free radical oxidation of SQ mainly formed two types of isomers, 2-OOH-SQ and 3-OOH-SQ. The addition of β-carotene during singlet oxygen oxidation, and the addition of α-tocopherol during free radical oxidation lead to a dose-dependent decrease in the formation of SQOOH isomers. Such results suggest that the analysis of SQOOH at the isomeric level allows for the determination of the cause of SQ oxidation in various samples, and provides a foothold for future studies concerning the prevention of SQ oxidation.