bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Moving‐Boundary Approach for Modeling 2‐D Gravity‐Driven Stable and Unstable Flow in Partially Wettable Soils
Authors: Brindt Naaran , Wallach Rony 
Published: January 2020

AbstractThe moving‐boundary approach, which has been successfully used to model stable and unstable 1‐D flow in initially dry soils of various contact angles (Brindt & Wallach, 2017 https://doi.org/10.1002/2016WR019252), was extended here for 2‐D flow. The wetting front is the plume perimeter that is partly formed by the capillary driving force, the remaining part by the combined capillary and gravity driving forces. The moving‐boundary approach overcomes the limitation of the Richards equation for describing gravity‐driven unstable flow with nonmonotonic water‐content distribution. According to this approach, the 2‐D flow domain is divided into two subdomains with a sharp change in fluid saturation between them—the wetting front (moving boundary). The 2‐D Richards equation was solved for the subdomain behind the wetting front for a given flux boundary condition at the soil surface, while the location of the other boundary, for which a no‐flux condition is imposed, was part of the solution. The moving‐boundary solution was used after verification to demonstrate the synergistic effect of contact angle and incoming flux on flow stability and its associated plume shapes. The contact angle that hinders spontaneous invasion of the dry pores decreases the water‐entry capillary pressure, ψwe, while the flux‐dependent dynamic water‐entry value, ψwed, is even lower, both inducing water accumulation behind the wetting front (saturation overshoot). This innovative physically based model for the 2‐D unsaturated flow problem for an initially dry soil of zero and nonzero contact angle using the moving‐boundary approach fulfills several criteria raised by researchers to adequately describe gravity‐driven unstable flow.
An ultra-stable cytoplasmic antibody engineered for in vivo applications
Authors: Kabayama Hiroyuki , Takeuchi Makoto , Tokushige Naoko , Muramatsu Shin-ichi , Kabayama Miyuki , Fukuda Mitsunori , Yamada Yoshiyuki , Mikoshiba Katsuhiko 
Published: January 2020

AbstractTargeting cytoplasmic protein–protein interactions with antibodies remains technically challenging, since antibodies expressed in the cytosol frequently form insoluble aggregates. Existing engineering methods are based on the notion that the estimated net charge at pH 7.4 affects stability; as such, they are unable to overcome this problem. Herein, we report a versatile method for engineering an ultra-stable cytoplasmic antibody (STAND), with a strong estimated net negative charge at pH 6.6, by fusing peptide tags with a highly negative charge and a low isoelectric point. Without the need for complicated amino acid substitutions, we convert aggregation-prone antibodies to STANDs that are useful for inhibiting in vivo transmitter release, modulating animal behaviour, and inhibiting in vivo cancer proliferation driven by mutated Kras—long recognised as an “undruggable” oncogenic protein. The STAND method shows promise for targeting endogenous cytoplasmic proteins in basic biology and for developing future disease treatments.
Ultrafast transient liquid assisted growth of high current density superconducting films
Authors: Soler L. , Jareño J. , Banchewski J. , Rasi S. , Chamorro N. , Guzman R. , Yáñez R. , Mocuta C. , Ricart S. , Farjas J. , Roura-Grabulosa P. , Obradors X. , Puig T. 
Published: January 2020

AbstractThe achievement of high growth rates in YBa2Cu3O7 epitaxial high-temperature superconducting films has become strategic to enable high-throughput manufacturing of long length coated conductors for energy and large magnet applications. We report on a transient liquid assisted growth process capable of achieving ultrafast growth rates (100 nm s−1) and high critical current densities (5 MA cm−2 at 77 K). This is based on the kinetic preference of Ba-Cu-O to form transient liquids prior to crystalline thermodynamic equilibrium phases, and as such is a non-equilibrium approach. The transient liquid-assisted growth process is combined with chemical solution deposition, proposing a scalable method for superconducting tapes manufacturing. Additionally, using colloidal solutions, the growth process is extended towards fabrication of nanocomposite films for enhanced superconducting properties at high magnetic fields. Fast acquisition in situ synchrotron X-ray diffraction and high resolution scanning transmission electron microscopy (STEM) become crucial measurements in disentangling key aspects of the growth process.
Mikania micrantha genome provides insights into the molecular mechanism of rapid growth
Authors: Liu Bo , Yan Jian , Li Weihua , Yin Lijuan , Li Ping , Yu Hanxia , Xing Longsheng , Cai Minling , Wang Hengchao , Zhao Mengxin , Zheng Jin , Sun Feng , Wang Zhenzhen , Jiang Zhaoyang , Ou Qiaojing , Li Shubin , Qu Lu , Zhang Qilei , Zheng Yaping , Qiao Xi , Xi Yu , Zhang Yan , Jiang Fan , Huang Cong , Liu Conghui , Ren Yuwei , Wang Sen , Liu Hangwei , Guo Jianyang , Wang Haihong , Dong Hui , Peng Changlian , Qian Wanqiang , Fan Wei , Wan Fanghao 
Published: January 2020

AbstractMikania micranthais one of the top 100 worst invasive species that can cause serious damage to natural ecosystems and substantial economic losses. Here, we present its 1.79 Gb chromosome-scale reference genome. Half of the genome is composed of long terminal repeat retrotransposons, 80% of which have been derived from a significant expansion in the past one million years. We identify a whole genome duplication event and recent segmental duplications, which may be responsible for its rapid environmental adaptation. Additionally, we show thatM. micranthaachieves higher photosynthetic capacity by CO2absorption at night to supplement the carbon fixation during the day, as well as enhanced stem photosynthesis efficiency. Furthermore, the metabolites ofM. micranthacan increase the availability of nitrogen by enriching the microbes that participate in nitrogen cycling pathways. These findings collectively provide insights into the rapid growth and invasive adaptation.
A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment
Authors: López Del Amo Víctor , Bishop Alena L. , Sánchez C. Héctor M. , Bennett Jared B. , Feng Xuechun , Marshall John M. , Bier Ethan , Gantz Valentino M. 
Published: January 2020

AbstractCRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and supporting ecosystem conservation efforts. Current technologies raise safety concerns for unintended gene propagation. Herein, we address such concerns by splitting the drive components, Cas9 and gRNAs, into separate alleles to form a trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes. This dual-component configuration allows for combinatorial transgene optimization and increases safety by restricting escape concerns to experimentation windows. We employ the tGD and a small–molecule-controlled version to investigate the biology of component inheritance and resistant allele formation, and to study the effects of maternal inheritance and impaired homology on efficiency. Lastly, mathematical modeling of tGD spread within populations reveals potential advantages for improving current gene-drive technologies for field population modification.
Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge
Authors: Tatebe Hisashi , Lim Chew Theng , Konno Hiroki , Shiozaki Kazuhiro , Shinohara Akira , Uchihashi Takayuki , Furukohri Asako 
Published: January 2020

AbstractThe human Mre11/Rad50 complex is one of the key factors in genome maintenance pathways. Previous nanoscale imaging by atomic force microscopy (AFM) showed that the ring-like structure of the human Mre11/Rad50 complex transiently opens at the zinc hook of Rad50. However, imaging of the human Mre11/Rad50 complex by high-speed AFM shows that the Rad50 coiled-coil arms are consistently bridged by the dimerized hooks while the Mre11/Rad50 ring opens by disconnecting the head domains; resembling other SMC proteins such as cohesin or condensin. These architectural features are conserved in the yeast and bacterial Mre11/Rad50 complexes. Yeast strains harboring the chimeric Mre11/Rad50 complex containing the SMC hinge of bacterial condensin MukB instead of the RAD50 hook properly functions in DNA repair. We propose that the basic role of the Rad50 hook is similar to that of the SMC hinge, which serves as rather stable dimerization interface.
Ultrafast shock synthesis of nanocarbon from a liquid precursor
Authors: Armstrong Michael R. , Lindsey Rebecca K. , Goldman Nir , Nielsen Michael H. , Stavrou Elissaios , Fried Laurence E. , Zaug Joseph M. , Bastea Sorin 
Published: January 2020

AbstractCarbon nanoallotropes are important nanomaterials with unusual properties and promising applications. High pressure synthesis has the potential to open new avenues for controlling and designing their physical and chemical characteristics for a broad range of uses but it remains little understood due to persistent conceptual and experimental challenges, in addition to fundamental physics and chemistry questions that are still unresolved after many decades. Here we demonstrate sub-nanosecond nanocarbon synthesis through the application of laser-induced shock-waves to a prototypical organic carbon-rich liquid precursor—liquid carbon monoxide. Overlapping large-scale molecular dynamics simulations capture the atomistic details of the nanoparticles’ formation and evolution in a reactive environment and identify classical evaporation-condensation as the mechanism governing their growth on these time scales.
A robust and efficient method for Mendelian randomization with hundreds of genetic variants
Authors: Burgess Stephen , Foley Christopher N , Allara Elias , Staley James R , Howson Joanna M. M. 
Published: January 2020

AbstractMendelian randomization (MR) is an epidemiological technique that uses genetic variants to distinguish correlation from causation in observational data. The reliability of a MR investigation depends on the validity of the genetic variants as instrumental variables (IVs). We develop the contamination mixture method, a method for MR with two modalities. First, it identifies groups of genetic variants with similar causal estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Second, it performs MR robustly and efficiently in the presence of invalid IVs. Compared to other robust methods, it has the lowest mean squared error across a range of realistic scenarios. The method identifies 11 variants associated with increased high-density lipoprotein-cholesterol, decreased triglyceride levels, and decreased coronary heart disease risk that have the same directions of associations with various blood cell traits, suggesting a shared mechanism linking lipids and coronary heart disease risk mediated via platelet aggregation.
TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh
Authors: Zhao Limin , Ke Hao , Xu Haibo , Wang Guo-Dong , Zhang Honglei , Zou Li , Xiang Shu , Li Mengyuan , Peng Li , Zhou Mingfang , Li Lingling , Ao Lei , Yang Qin , Shen Che-Kun James , Yi Ping , Wang Lu , Jiao Baowei 
Published: January 2020

AbstractMilk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation ofBtn1a1andXdhmRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.
Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform
Authors: Da Li  , Cao Tiefeng , Sun Xiaoli , Jin Sungho , Di Xie  , Huang Xinmei , Yang Xiaoyong , Carmichael Gordon G. , Taylor Hugh S. , Diano Sabrina , Huang Yingqun 
Published: January 2020

AbstractPrecise control of hepatic glucose production (HGP) is pivotal to maintain systemic glucose homeostasis. HNF4α functions to stimulate transcription of key gluconeogenic genes. HNF4α harbors two promoters (P2 and P1) thought to be primarily active in fetal and adult livers, respectively. Here we report that the fetal version of HNF4α is required for HGP in the adult liver. This isoform is acutely induced upon fasting and chronically increased in type-2 diabetes (T2D). P2 isoform induction occurs in response to glucagon-stimulated upregulation of TET3, not previously shown to be involved in HGP. TET3 is recruited to the P2 promoter by FOXA2, leading to promoter demethylation and increased transcription. While TET3 overexpression augments HGP, knockdown of either TET3 or the P2 isoform alone in the liver improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies unmask an unanticipated, conserved regulatory mechanism in HGP and offer potential therapeutic targets for T2D.
Cerebrospinal fluid tracer efflux to parasagittal dura in humans
Authors: Ringstad Geir , Eide Per Kristian 
Published: January 2020

AbstractThe mechanisms behind molecular transport from cerebrospinal fluid to dural lymphatic vessels remain unknown. This study utilized magnetic resonance imaging along with cerebrospinal fluid tracer to visualize clearance pathways to human dural lymphatics in vivo. In 18 subjects with suspicion of various types of cerebrospinal fluid disorders, 3D T2-Fluid Attenuated Inversion Recovery, T1-black-blood, and T1 gradient echo acquisitions were obtained prior to intrathecal administration of the contrast agent gadobutrol (0.5 ml, 1 mmol/ml), serving as a cerebrospinal fluid tracer. Propagation of tracer was followed with T1 sequences at 3, 6, 24 and 48 h after the injection. The tracer escaped from cerebrospinal fluid into parasagittal dura along the superior sagittal sinus at areas nearby entry of cortical cerebral veins. The findings demonstrate that trans-arachnoid molecular passage does occur and suggest that parasagittal dura may serve as a bridging link between human brain and dural lymphatic vessels.
A transcriptome-wide antitermination mechanism sustaining identity of embryonic stem cells
Authors: Kainov Yaroslav A. , Makeyev Eugene V. 
Published: January 2020

AbstractEukaryotic gene expression relies on extensive crosstalk between transcription and RNA processing. Changes in this composite regulation network may provide an important means for shaping cell type-specific transcriptomes. Here we show that the RNA-associated protein Srrt/Ars2 sustains embryonic stem cell (ESC) identity by preventing premature termination of numerous transcripts at cryptic cleavage/polyadenylation sites in first introns. Srrt interacts with the nuclear cap-binding complex and facilitates recruitment of the spliceosome component U1 snRNP to cognate intronic positions. At least in some cases, U1 recruited in this manner inhibits downstream cleavage/polyadenylation events through a splicing-independent mechanism called telescripting. We further provide evidence that the naturally high expression of Srrt in ESCs offsets deleterious effects of retrotransposable sequences accumulating in its targets. Our work identifies Srrt as a molecular guardian of the pluripotent cell state.
Large-area, periodic, and tunable intrinsic pseudo-magnetic fields in low-angle twisted bilayer graphene
Authors: Shi Haohao , Zhan Zhen , Qi Zhikai , Huang Kaixiang , Veen Edo van , Silva-Guillén Jose Ángel , Zhang Runxiao , Li Pengju , Xie Kun , Ji Hengxing , Katsnelson Mikhail I. , Yuan Shengjun , Qin Shengyong , Zhang Zhenyu 
Published: January 2020

AbstractA properly strained graphene monolayer or bilayer is expected to harbour periodic pseudo-magnetic fields with high symmetry, yet to date, a convincing demonstration of such pseudo-magnetic fields has been lacking, especially for bilayer graphene. Here, we report a definitive experimental proof for the existence of large-area, periodic pseudo-magnetic fields, as manifested by vortex lattices in commensurability with the moiré patterns of low-angle twisted bilayer graphene. The pseudo-magnetic fields are strong enough to confine the massive Dirac electrons into circularly localized pseudo-Landau levels, as observed by scanning tunneling microscopy/spectroscopy, and also corroborated by tight-binding calculations. We further demonstrate that the geometry, amplitude, and periodicity of the pseudo-magnetic fields can be fine-tuned by both the rotation angle and heterostrain. Collectively, the present study substantially enriches twisted bilayer graphene as a powerful enabling platform for exploration of new and exotic physical phenomena, including quantum valley Hall effects and quantum anomalous Hall effects.
A simple and versatile nickel platform for the generation of branched high molecular weight polyolefins
Authors: Liang Tao , Goudari Shabnam B. , Chen Changle 
Published: January 2020

AbstractThe development of high-performance transition metal catalysts has long been a major driving force in academic and industrial polyolefin research. Late transition metal-based olefin polymerization catalysts possess many unique properties, such as the ability to generate variously branched polyolefins using only ethylene as the feedstock and the capability of incorporating polar functionalized comonomers without protecting agents. Here we report the synthesis and (co)polymerization studies of a simple but extremely versatile α-imino-ketone nickel system. This type of catalyst is easy to synthesize and modify, and it is thermally stable and highly active during ethylene polymerization without the addition of any cocatalysts. Despite the sterically open nature, these catalysts can generate branched Ultra-High-Molecular-Weight polyethylene and copolymerize ethylene with a series of polar comonomers. The versatility of this platform has been further demonstrated through the synthesis of a dinuclear nickel catalyst and the installation of an anchor for catalyst heterogenization.
Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2
Authors: Zhou Zhang-Sen , Li Mei-Xin , Liu Jie , Jiao Hengwu , Xia Jing-Ming , Shi Xiong-Jie , Zhao Huabin , Chu Liping , Liu Jingrong , Qi Wei , Luo Jie , Song Bao-Liang 
Published: January 2020

AbstractInsig-2 is an ER membrane protein negatively controlling lipid biosynthesis. Here, we find that Insig-2 is increased in the tissues, including liver, but unaltered in the muscle of gp78-deficient mice. In hepatocytes and undifferentiated C2C12 myoblasts, Insig-2 is ubiquitylated on Cys215 by gp78 and degraded. However, the C215 residue is oxidized by elevated reactive oxygen species (ROS) during C2C12 myoblasts differentiating into myotubes, preventing Insig-2 from ubiquitylation and degradation. The stabilized Insig-2 downregulates lipogenesis through inhibiting the SREBP pathway, helping to channel the carbon flux to ATP generation and protecting myotubes from lipid over-accumulation. Evolutionary analysis shows that the YECK (in which C represents Cys215 in human Insig-2) tetrapeptide sequence in Insig-2 is highly conserved in amniotes but not in aquatic amphibians and fishes, suggesting it may have been shaped by differential selection. Together, this study suggests that competitive oxidation-ubiquitylation on Cys215 of Insig-2 senses ROS and prevents muscle cells from lipid accumulation.
Bacterial Hsp70 resolves misfolded states and accelerates productive folding of a multi-domain protein
Authors: Imamoglu Rahmi , Balchin David , Hayer-Hartl Manajit , Hartl F. Ulrich 
Published: January 2020

AbstractThe ATP-dependent Hsp70 chaperones (DnaK in E. coli) mediate protein folding in cooperation with J proteins and nucleotide exchange factors (E. coli DnaJ and GrpE, respectively). The Hsp70 system prevents protein aggregation and increases folding yields. Whether it also enhances the rate of folding remains unclear. Here we show that DnaK/DnaJ/GrpE accelerate the folding of the multi-domain protein firefly luciferase (FLuc) ~20-fold over the rate of spontaneous folding measured in the absence of aggregation. Analysis by single-pair FRET and hydrogen/deuterium exchange identified inter-domain misfolding as the cause of slow folding. DnaK binding expands the misfolded region and thereby resolves the kinetically-trapped intermediates, with folding occurring upon GrpE-mediated release. In each round of release DnaK commits a fraction of FLuc to fast folding, circumventing misfolding. We suggest that by resolving misfolding and accelerating productive folding, the bacterial Hsp70 system can maintain proteins in their native states under otherwise denaturing stress conditions.
Superior polarization retention through engineered domain wall pinning
Authors: Zhang Dawei , Sando Daniel , Sharma Pankaj , Cheng Xuan , Ji Fan , Govinden Vivasha , Weyland Matthew , Nagarajan Valanoor , Seidel Jan 
Published: January 2020

AbstractFerroelectric materials possess a spontaneous polarization that is switchable by an electric field. Robust retention of switched polarization is critical for non-volatile nanoelectronic devices based on ferroelectrics, however, these materials often suffer from polarization relaxation, typically within days to a few weeks. Here we exploit designer-defect-engineered epitaxial BiFeO3 films to demonstrate polarization retention with virtually no degradation in switched nanoscale domains for periods longer than 1 year. This represents a more than 2000% improvement over the best values hitherto reported. Scanning probe microscopy-based dynamic switching measurements reveal a significantly increased activation field for domain wall movement. Atomic resolution scanning transmission electron microscopy indicates that nanoscale defect pockets pervade the entire film thickness. These defects act as highly efficient domain wall pinning centres, resulting in anomalous retention. Our findings demonstrate that defects can be exploited in a positive manner to solve reliability issues in ferroelectric films used in functional devices.