bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme differences between human germline and tumor mutation densities are driven by ancestral human-specific deviations
Authors: Heredia-Genestar José María , Marquès-Bonet Tomàs , Juan David , Navarro Arcadi 
Published: May 2020

AbstractMutations do not accumulate uniformly across the genome. Human germline and tumor mutation density correlate poorly, and each is associated with different genomic features. Here, we use non-human great ape (NHGA) germlines to determine human germline- and tumor-specific deviations from an ancestral-like great ape genome-wide mutational landscape. Strikingly, we find that the distribution of mutation densities in tumors presents a stronger correlation with NHGA than with human germlines. This effect is driven by human-specific differences in the distribution of mutations at non-CpG sites. We propose that ancestral human demographic events, together with the human-specific mutation slowdown, disrupted the human genome-wide distribution of mutation densities. Tumors partially recover this distribution by accumulating preneoplastic-like somatic mutations. Our results highlight the potential utility of using NHGA population data, rather than human controls, to establish the expected mutational background of healthy somatic cells.
HOX13-dependent chromatin accessibility underlies the transition towards the digit development program
Authors: Desanlis Ines , Kherdjemil Yacine , Mayran Alexandre , Bouklouch Yasser , Gentile Claudia , Sheth Rushikesh , Zeller Rolf , Drouin Jacques , Kmita Marie 
Published: May 2020

AbstractHox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromatin context on HOX binding specificity remains elusive. Here, we used the developing limb as a model system to compare the binding specificity of HOXA13 and HOXD13 (HOX13 hereafter), which are required for digit formation, and HOXA11, involved in forearm/leg development. We find that upon ectopic expression in distal limb buds, HOXA11 binds sites normally HOX13-specific. Importantly, these sites are loci whose chromatin accessibility relies on HOX13. Moreover, we show that chromatin accessibility specific to the distal limb requires HOX13 function. Based on these results, we propose that HOX13 TFs pioneer the distal limb-specific chromatin accessibility landscape for the proper implementation of the distal limb developmental program.
The mutational impact of culturing human pluripotent and adult stem cells
Authors: Kuijk Ewart , Jager Myrthe , van der Roest Bastiaan , Locati Mauro D. , Van Hoeck Arne , Korzelius Jerome , Janssen Roel , Besselink Nicolle , Boymans Sander , van Boxtel Ruben , Cuppen Edwin 
Published: May 2020

AbstractGenetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies.
Allele-aware chromosome-level genome assembly and efficient transgene-free genome editing for the autotetraploid cultivated alfalfa
Authors: Chen Haitao , Zeng Yan , Yang Yongzhi , Huang Lingli , Tang Bolin , Zhang He , Hao Fei , Liu Wei , Li Youhan , Liu Yanbin , Zhang Xiaoshuang , Zhang Ru , Zhang Yesheng , Li Yongxin , Wang Kun , He Hua , Wang Zhongkai , Fan Guangyi , Yang Hui , Bao Aike , Shang Zhanhuan , Chen Jianghua , Wang Wen , Qiu Qiang 
Published: May 2020

AbstractArtificially improving traits of cultivated alfalfa (Medicago sativaL.), one of the most important forage crops, is challenging due to the lack of a reference genome and an efficient genome editing protocol, which mainly result from its autotetraploidy and self-incompatibility. Here, we generate an allele-aware chromosome-level genome assembly for the cultivated alfalfa consisting of 32 allelic chromosomes by integrating high-fidelity single-molecule sequencing and Hi-C data. We further establish an efficient CRISPR/Cas9-based genome editing protocol on the basis of this genome assembly and precisely introduce tetra-allelic mutations into null mutants that display obvious phenotype changes. The mutated alleles and phenotypes of null mutants can be stably inherited in generations in a transgene-free manner by cross pollination, which may help in bypassing the debate about transgenic plants. The presented genome and CRISPR/Cas9-based transgene-free genome editing protocol provide key foundations for accelerating research and molecular breeding of this important forage crop.
Unstable twin in body-centered cubic tungsten nanocrystals
Authors: Wang Xiang , Wang Jiangwei , He Yang , Wang Chongmin , Zhong Li , Mao Scott X. 
Published: May 2020

AbstractTwinning is commonly activated in plastic deformation of low stacking-fault face-centered cubic (Fcc) metals but rarely found in body-centered cubic (Bcc) metals under room temperature and slow strain rates. Here, by conducting in situ transmission electron microscopy (TEM) at atomic scale, we discover that, in stark contrast to those in most Fcc metals, a majority of deformation twins in Bcc metals are unstable and undergo spontaneously detwinning upon unloading. Such unexpected instability of Bcc twins is found to be closely related to the prevalence of the inclined twin boundaries—a peculiar structure where twin boundaries are not parallel to the twinning plane, and the degree of instability is in direct proportion to the fraction of the inclined twin boundary. This work provides significant insights into the structure and stability of deformation twins in Bcc metals.
Ultrathin high-κ antimony oxide single crystals
Authors: Yang Kena , Zhang Tao , Wei Bin , Bai Yijia , Jia Shuangfeng , Cao Guanghui , Jiang Renhui , Zhang Chunbo , Gao Enlai , Chang Xuejiao , Li Juntao , Li Simo , Zhu Daming , Tai Renzhong , Zhou Hua , Wang Jianbo , Zeng Mengqi , Wang Zhongchang , Fu Lei 
Published: May 2020

AbstractUltrathin oxides have been reported to possess excellent properties in electronic, magnetic, optical, and catalytic fields. However, the current and primary approaches toward the preparation of ultrathin oxides are only applicable to amorphous or polycrystalline oxide nanosheets or films. Here, we successfully synthesize high-quality ultrathin antimony oxide single crystals via a substrate-buffer-controlled chemical vapor deposition strategy. The as-obtained ultrathin antimony oxide single crystals exhibit high dielectric constant (~100) and large breakdown voltage (~5.7 GV m−1). Such a strategy can also be utilized to fabricate other ultrathin oxides, opening up an avenue in broadening the applicaitons of ultrathin oxides in many emerging fields.
Component response rate variation underlies the stability of highly complex finite systems
Authors: Duthie A. Bradley 
Published: May 2020

AbstractThe stability of a complex system generally decreases with increasing system size and interconnectivity, a counterintuitive result of widespread importance across the physical, life, and social sciences. Despite recent interest in the relationship between system properties and stability, the effect of variation in response rate across system components remains unconsidered. Here I vary the component response rates (γ) of randomly generated complex systems. I use numerical simulations to show that when component response rates vary, the potential for system stability increases. These results are robust to common network structures, including small-world and scale-free networks, and cascade food webs. Variation in γ is especially important for stability in highly complex systems, in which the probability of stability would otherwise be negligible. At such extremes of simulated system complexity, the largest stable complex systems would be unstable if not for variation in γ. My results therefore reveal a previously unconsidered aspect of system stability that is likely to be pervasive across all realistic complex systems.
The pressure to communicate efficiently continues to shape language use later in life
Authors: Long Madeleine , Rohde Hannah , Rubio-Fernandez Paula 
Published: May 2020

AbstractLanguage use is shaped by a pressure to communicate efficiently, yet the tendency towards redundancy is said to increase in older age. The longstanding assumption is that saying more than is necessary is inefficient and may be driven by age-related decline in inhibition (i.e. the ability to filter out irrelevant information). However, recent work proposes an alternative account of efficiency: In certain contexts, redundancy facilitates communication (e.g., when the colour or size of an object is perceptually salient and its mention aids the listener’s search). A critical question follows: Are older adults indiscriminately redundant, or do they modulate their use of redundant information to facilitate communication? We tested efficiency and cognitive capacities in 200 adults aged 19–82. Irrespective of age, adults with better attention switching skills were redundant in efficient ways, demonstrating that the pressure to communicate efficiently continues to shape language use later in life.
Comparison of Three Histological Techniques for Fat Emboli Detection in Lung Cetacean’s Tissue
Authors: Arregui Marina , Fernández Antonio , Paz-Sánchez Yania , Santana Ángelo , Sacchini Simona , Sierra Eva , Arbelo Manuel , de Quirós Yara Bernaldo 
Published: May 2020

AbstractFat embolism is the mechanical blockage of blood vessels by circulating fat particles. It is frequently related to traumas involving soft tissues and fat-containing bones. Different techniques have been used for decades to demonstrate histologically fat emboli, being the extremely toxic post-fixation with osmium tetroxide one of the most used techniques in the last decades. In the present study, the osmium tetroxide technique was compared qualitatively and quantitatively, for the first time, with chromic acid and Oil Red O frozen techniques for histological fat emboli detection in the lungs of eight sperm whales that died due to ship strikes. This was also the first time that chromic acid technique was tested in cetaceans. Results showed that the three techniques were valuable for the histological detection of fat embolism in cetaceans, even when tissues presented advanced autolysis and had been stored in formaldehyde for years. Although quantitative differences could not be established, the Oil Red O frozen technique showed the lowest quality for fat emboli staining. On the contrary, the chromic acid technique was proven to be a good alternative to osmium tetroxide due to its slightly lower toxicity, its equivalent or even superior capacity of fat emboli detection, and its significantly lower economic cost.
State dependence and temporal evolution of resistance in projected phase change memory
Authors: Kersting Benedikt , Ovuka Vladimir , Jonnalagadda Vara Prasad , Sousa Marilyne , Bragaglia Valeria , Sarwat Syed Ghazi , Le Gallo Manuel , Salinga Martin , Sebastian Abu 
Published: May 2020

AbstractPhase change memory (PCM) is being actively explored for in-memory computing and neuromorphic systems. The ability of a PCM device to store a continuum of resistance values can be exploited to realize arithmetic operations such as matrix-vector multiplications or to realize the synaptic efficacy in neural networks. However, the resistance variations arising from structural relaxation, 1/f noise, and changes in ambient temperature pose a key challenge. The recently proposed projected PCM concept helps to mitigate these resistance variations by decoupling the physical mechanism of resistance storage from the information-retrieval process. Even though the device concept has been proven successfully, a comprehensive understanding of the device behavior is still lacking. Here, we develop a device model that captures two key attributes, namely, resistance drift and the state dependence of resistance. The former refers to the temporal evolution of resistance, while the latter refers to the dependence of the device resistance on the phase configuration of the phase change material. The study provides significant insights into the role of interfacial resistance in these devices. The model is experimentally validated on projected PCM devices based on antimony and a metal nitride fabricated in a lateral device geometry and is also used to provide guidelines for material selection and device engineering.
Aggregation of M3 (E376D) variant of alpha1- antitrypsin
Authors: Bashir Arif , Hazari Younis , Pal Debnath , Maity Dibyajyoti , Bashir Samirul , Singh Laishram Rajendrakumar , Shah Naveed Nazir , Fazili Khalid Majid 
Published: May 2020

AbstractAlpha1-antitrypsin (α1AT) is an abundant serine-protease inhibitor in circulation. It has an important role in neutralizing the neutrophil elastase activity. Different pathogenic point mutations like Z(E342K)-α1AT have been implicated in the development of liver cirrhosis and Chronic Obstructive Pulmonary Disease (COPD), the latter being a cluster of progressive lung diseases including chronic bronchitis and emphysema. M3-α1AT (376Glu > Asp) is another variant of α1AT which so far is largely being considered as normal though increased frequency of the variant has been reported in many human diseases including COPD. We also observed increased frequency of M3-α1AT in COPD cases in Kashmiri population. The frequency of heterozygous (AC) genotype in cases and controls was 58.57% and 27.61% (odds-ratio 6.53 (2.27–15.21); p < 0.0001) respectively, while homozygous CC genotype was found to be 21.42% and 6.66% (odds-ratio 10.56 (3.63–18.64); p < 0.0001) respectively. Comparative in vitro investigations that include trypsin‒antitrypsin assay, Circular Dichroism spectroscopy and dynamic light scattering performed on wild-type (M-α1AT), M3-α1AT, and Z-α1AT proteins along with the molecular dynamics simulations revealed that M3-α1AT has properties similar to Z-α1AT capable of forming aggregates of varied size. Our maiden observations suggest that M3-α1AT may contribute to the pathogenesis of COPD and other disorders by mechanisms that warrant further investigations.
Intermittent Use of a Short-Course Glucagon-like Peptide-1 Receptor Agonist Therapy Limits Adverse Cardiac Remodeling via Parkin-dependent Mitochondrial Turnover
Authors: Germano Juliana de F. , Huang Chengqun , Sin Jon , Song Yang , Tucker Kyle C. , Taylor David J. R. , Saadaeijahromi Hannaneh , Stotland Aleksandr , Piplani Honit , Gottlieb Roberta A. , Mentzer Robert M. , Andres Allen M. 
Published: May 2020

AbstractGiven that adverse remodeling is the leading cause of heart failure and death in the USA, there is an urgent unmet need to develop new methods in dealing with this devastating disease. Here we evaluated the efficacy of a short-course glucagon-like peptide-1 receptor agonist therapy—specifically 2-quinoxalinamine, 6,7-dichloro-N-(1,1-dimethylethyl)-3-(methylsulfonyl)-,6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB; aka Compound 2) – in attenuating adverse LV remodeling. We also examined the role, if any, of mitochondrial turnover in this process. Wild-type, Parkin knockout and MitoTimer-expressing mice were subjected to permanent coronary artery ligation, then treated briefly with DMB. LV remodeling and cardiac function were assessed by histology and echocardiography. Autophagy and mitophagy markers were examined by western blot and mitochondrial biogenesis was inferred from MitoTimer protein fluorescence and qPCR. We found that DMB given post-infarction significantly reduced adverse LV remodeling and the decline of cardiac function. This paralleled an increase in autophagy, mitophagy and mitochondrial biogenesis. The salutary effects of the drug were lost in Parkin knockout mice, implicating Parkin-mediated mitophagy as part of its mechanism of action. Our findings suggest that enhancing Parkin-associated mitophagy and mitochondrial biogenesis after infarction is a viable target for therapeutic mitigation of adverse remodeling.
Nonlinear compositional and morphological evolution of ion irradiated GaSb prior to nanostructure formation
Authors: Lively Michael A. , Holybee Brandon , Toriyama Michael , Facsko Stefan , Allain Jean Paul 
Published: May 2020

AbstractLow-energy ion irradiation of III-V semiconductor surfaces can lead to the formation of regular hexagonal dot patterns at the surface. We present experimental and computational results for ion irradiation of GaSb surfaces which elucidate the nature of the coupled compositional and morphological pattern-formation mechanisms. We demonstrate by in-situ grazing-incidence small-angle x-ray scattering (GISAXS) and angle-resolved Auger electron spectroscopy (ARAES) that the emergence of an altered compositional depth profile is essential to induce morphological changes at the surface. This morphological evolution of the surface follows nucleation-and-growth kinetics. Furthermore, we show from massive-scale molecular dynamics (MD) simulations that the compositional depth profile evolution leads to thermodynamic phase separation, providing a lateral compositional instability that drives pattern formation. Additionally, high-fluence simulations elucidate the irradiation-induced mechanisms of compositional depth profile formation. Prompt ion effects drive formation of single-element “protoclusters”, predominantly of Sb. Structural and energetic characterization of the simulation results indicate that Sb may be more mobile than Ga, providing a diffusional pathway for long-temporal-scale compositional evolution of the irradiated surface. Our findings motivate the development of new, comprehensive models which consider the total spatial and temporal complexity of multicomponent systems evolving under ion irradiation.
Rapid pyritization in the presence of a sulfur/sulfate-reducing bacterial consortium
Authors: Berg Jasmine S. , Duverger Arnaud , Cordier Laure , Laberty-Robert Christel , Guyot François , Miot Jennyfer 
Published: May 2020

AbstractSedimentary pyrite (FeS2) is commonly thought to be a product of microbial sulfate reduction and hence may preserve biosignatures. However, proof that microorganisms are involved in pyrite formation is still lacking as only metastable iron sulfides are usually obtained in laboratory cultures. Here we show the rapid formation of large pyrite spherules through the sulfidation of Fe(III)-phosphate (FP) in the presence of a consortium of sulfur- and sulfate-reducing bacteria (SRB), Desulfovibrio and Sulfurospirillum, enriched from ferruginous and phosphate-rich Lake Pavin water. In biomineralization experiments inoculated with this consortium, pyrite formation occurred within only 3 weeks, likely enhanced by the local enrichment of polysulfides around SRB cells. During this same time frame, abiotic reaction of FP with sulfide led to the formation of vivianite (Fe3(PO4)2·8H2O) and mackinawite (FeS) only. Our results suggest that rates of pyritization vs. vivianite formation are regulated by SRB activity at the cellular scale, which enhances phosphate release into the aqueous phase by increased efficiency of iron sulfide precipitation, and thus that these microorganisms strongly influence biological productivity and Fe, S and P cycles in the environment.
Effects of a partner’s tap intervals on an individual’s timing control increase in slow-tempo dyad synchronisation using finger-tapping
Authors: Kimura Kazuto , Ogata Taiki , Miyake Yoshihiro 
Published: May 2020

AbstractIn musical ensembles, musicians synchronise their movements with other members of the ensemble at various tempos. This study aims to investigate the extent of tempo dependency of own and partner’s timing information on rhythm production. We conducted a dyad synchronisation-continuous finger-tapping task. First, two participants synchronised with the same auditory metronome at various tempos. Subsequently, after stopping the metronome, the participants maintained the tempo with the presentation of the partner’s tap timing via auditory signals. This task was conducted in six metronome tempo conditions at 700 to 3,200 ms in 500 ms step. It was found that the partner’s previous inter-tap intervals increased as the metronome tempo decreased. The effects of own previous inter-tap intervals and synchronisation errors between own and the partner’s tap timing did not depend on the metronome tempo. Therefore, timing control in dyad synchronisation was affected by the partner’s tempo more strongly in slow than fast tempos. This strong effect of the partner in slow-tempo rhythm synchronisation could be due to stronger attention to the partner’s movement timing in slower tempos than in fast tempos.
3D Bioprinting of osteochondral tissue substitutes – in vitro-chondrogenesis in multi-layered mineralized constructs
Authors: Kilian David , Ahlfeld Tilman , Akkineni Ashwini Rahul , Bernhardt Anne , Gelinsky Michael , Lode Anja 
Published: May 2020

AbstractFor the generation of multi-layered full thickness osteochondral tissue substitutes with an individual geometry based on clinical imaging data, combined extrusion-based 3D printing (3D plotting) of a bioink laden with primary chondrocytes and a mineralized biomaterial phase was introduced. A pasty calcium phosphate cement (CPC) and a bioink based on alginate-methylcellulose (algMC) – both are biocompatible and allow 3D plotting with high shape fidelity – were applied in monophasic and combinatory design to recreate osteochondral tissue layers. The capability of cells reacting to chondrogenic biochemical stimuli inside the algMC-based 3D hydrogel matrix was assessed. Towards combined osteochondral constructs, the chondrogenic fate in the presence of CPC in co-fabricated and biphasic mineralized pattern was evaluated. Majority of expanded and algMC-encapsulated cells survived the plotting process and the cultivation period, and were able to undergo redifferentiation in the provided environment to produce their respective extracellular matrix (ECM) components (i.e. sulphated glycosaminoglycans, collagen type II), examined after 3 weeks. The presence of a mineralized zone as located in the physiological calcified cartilage region suspected to interfere with chondrogenesis, was found to support chondrogenic ECM production by altering the ionic concentrations of calcium and phosphorus in in vitro culture conditions.