bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partitioning of Crystalline and Amorphous Phases During Freezing of Simulated Enceladus Ocean Fluids
Authors: Fox‐Powell Mark G. , Cousins Claire R. 
Published: November 2020

AbstractSaturn's ice‐covered moon Enceladus may contain the requisite conditions for life. Its potentially habitable subsurface ocean is vented into space as large cryovolcanic plumes that can be sampled by spacecraft, acting as a window to the ocean below. However, little is known about how Enceladus’ ocean fluids evolve as they freeze. Using cryo‐imaging techniques, we investigated solid phases produced by freezing simulated Enceladean ocean fluids at endmember cooling rates. Our results show that under flash‐freezing conditions (>10 K s−1), Enceladus‐relevant fluids undergo segregation, whereby the precipitation of ice templates the formation of brine vein networks. The high solute concentrations and confined nature of these brine veins means that salt crystallization is kinetically inhibited and glass formation (vitrification) can occur at lower cooling rates than typically required for vitrification of a bulk solution. Crystalline salts also form if flash‐frozen fluids are re‐warmed. The 10 µm‐scale distribution of salt phases produced by this mechanism differs markedly from that of gradually cooled (∼1 K min−1) fluids, showing that they inherit a textural signature of their formation conditions. The mineralogy of cryogenic carbonates can be used as a probe for cooling rate and parent fluid pH. Our findings reveal possible endmember routes for solid phase production from Enceladus’ ocean fluids and mechanisms for generating compositional heterogeneity within ice particles on a sub‐10 µm scale. This has implications for understanding how Enceladus' ocean constituents are incorporated into icy particles and delivered to space.
Emission of Greenhouse Gases From Water Tracks Draining Arctic Hillslopes
Authors: Harms Tamara K. , Rocher‐Ros Gerard , Godsey Sarah E. 
Published: November 2020

AbstractExperimental and ambient warming of Arctic tundra results in emissions of greenhouse gases to the atmosphere, contributing to a positive feedback to climate warming. Estimates of gas emissions from lakes and terrestrial tundra confirm the significance of aquatic fluxes in greenhouse gas budgets, whereas few estimates describe emissions from fluvial networks. We measured dissolved gas concentrations and estimated emissions of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) from water tracks, vegetated depressions that hydrologically connect hillslope soils to lakes and streams. Concentrations of trace gases generally increased as ground thaw deepened through the growing season, indicating active production of greenhouse gases in thawed soils. Wet antecedent conditions were correlated with a decline in CO2 and CH4 concentrations. Dissolved N2O in excess of atmospheric equilibrium occurred in drier water tracks, but on average water tracks took up N2O from the atmosphere at low rates. Estimated CO2 emission rates for water tracks were among the highest observed for Arctic aquatic ecosystems, whereas CH4 emissions were of similar magnitude to streams. Despite occupying less than 1% of total catchment area, surface waters within water tracks were an estimated source of up to 53–85% of total CH4 emissions from their catchments and offset the terrestrial C sink by 5–9% during the growing season. Water tracks are abundant features of tundra landscapes that contain warmer soils and incur deeper thaw than adjacent terrestrial ecosystems and as such might contribute to ongoing and accelerating release of greenhouse gases from permafrost soils to the atmosphere.
Bioinformatics identification and pharmacological validation of Kcnn3/KCa2 channels as a mediator of negative affective behaviors and excessive alcohol drinking in mice
Authors: Padula Audrey E. , Rinker Jennifer A. , Lopez Marcelo F. , Mulligan Megan K. , Williams Robert W. , Becker Howard C. , Mulholland Patrick J. 
Published: November 2020

AbstractMood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in the development and maintenance of alcohol dependence and relapse. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy drinking and negative affective behaviors. In order to identify novel pharmacogenetic targets, a bioinformatics analysis was used to quantify the expression of amygdala K+ channel genes that covary with anxiety-related phenotypes in the well-phenotyped and fully sequenced family of BXD strains. We used a model of stress-induced escalation of drinking in alcohol-dependent mice to measure negative affective behaviors during abstinence. A pharmacological approach was used to validate the key bioinformatics findings in alcohol-dependent, stressed mice. Amygdalar expression of Kcnn3 correlated significantly with 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for anxiety-like behaviors and negative correlations with binge-like and voluntary alcohol drinking. Mice treated with chronic intermittent alcohol exposure and repeated swim stress consumed more alcohol in their home cages and showed hypophagia on the novelty-suppressed feeding test during abstinence. Pharmacologically targeting Kcnn gene products with the KCa2 (SK) channel-positive modulator 1-EBIO decreased drinking and reduced feeding latency in alcohol-dependent, stressed mice. Collectively, these validation studies provide central nervous system links into the covariance of stress, negative affective behaviors, and AUD in the BXD strains. Further, the bioinformatics discovery tool is effective in identifying promising targets (i.e., KCa2 channels) for treating alcohol dependence exacerbated by comorbid mood disorders.
Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846
Authors: Sugano Teppei , Masuda Mari , Takeshita Fumitaka , Motoi Noriko , Hirozane Toru , Goto Naoko , Kashimoto Shigeki , Uno Yuko , Moriyama Hideki , Sawa Masaaki , Nagakawa Yuichi , Tsuchida Akihiko , Seike Masahiro , Gemma Akihiko , Yamada Tesshi 
Published: November 2020

Abstract
Background
Metastasis is the primary cause of death in cancer patients, and its management is still a major challenge. Epithelial to mesenchymal transition (EMT) has been implicated in the process of cancer metastasis, and its pharmacological interference holds therapeutic promise.

Methods
Traf2- and Nck-interacting kinase (TNIK) functions as a transcriptional coregulator of Wnt target genes. Given the convergence of Wnt and transforming growth factor-β (TGFβ) signalling, we examined the effects of a small-molecule TNIK inhibitor (named NCB-0846) on the TGFβ1-induced EMT of lung cancer cells.

Results
NCB-0846 inhibited the TGFβ1-induced EMT of A549 cells. This inhibition was associated with inhibition of Sma- and Mad-Related Protein-2/3 (SMAD2/3) phosphorylation and nuclear translocation. NCB-0846 abolished the lung metastasis of TGFβ1-treated A549 cells injected into the tail veins of immunodeficient mice. The inhibition of EMT was mediated by suppression of the TGFβ receptor type-I (TGFBR1) gene, at least partly through the induction of microRNAs targeting the TGFBR1 transcript [miR-320 (a, b and d) and miR-186].

Conclusions
NCB-0846 pharmacologically blocks the TGFβ/SMAD signalling and EMT induction of lung cancer cells by transcriptionally downregulating TGFBRI expression, representing a potentially promising approach for prevention of metastasis in lung cancer patients.
A Cas-embedding strategy for minimizing off-target effects of DNA base editors
Authors: Liu Yajing , Zhou Changyang , Huang Shisheng , Dang Lu , Wei Yu , He Jun , Zhou Yingsi , Mao Shaoshuai , Tao Wanyu , Zhang Yu , Yang Hui , Huang Xingxu , Chi Tian 
Published: November 2020

AbstractDNA base editors, typically comprising editing enzymes fused to the N-terminus of nCas9, display off-target effects on DNA and/or RNA, which have remained an obstacle to their clinical applications. Off-target edits are typically countered via rationally designed point mutations, but the approach is tedious and not always effective. Here, we report that the off-target effects of both A > G and C > T editors can be dramatically reduced without compromising the on-target editing simply by inserting the editing enzymes into the middle of nCas9 at tolerant sites identified using a transposon-based genetic screen. Furthermore, employing this Cas-embedding strategy, we have created a highly specific editor capable of efficient C > T editing at methylated and GC-rich sequences.
The structural basis of promiscuity in small multidrug resistance transporters
Authors: Kermani Ali A. , Macdonald Christian B. , Burata Olive E. , Ben Koff B. , Koide Akiko , Denbaum Eric , Koide Shohei , Stockbridge Randy B. 
Published: November 2020

AbstractBy providing broad resistance to environmental biocides, transporters from the small multidrug resistance (SMR) family drive the spread of multidrug resistance cassettes among bacterial populations. A fundamental understanding of substrate selectivity by SMR transporters is needed to identify the types of selective pressures that contribute to this process. Using solid-supported membrane electrophysiology, we find that promiscuous transport of hydrophobic substituted cations is a general feature of SMR transporters. To understand the molecular basis for promiscuity, we solved X-ray crystal structures of a SMR transporter Gdx-Clo in complex with substrates to a maximum resolution of 2.3 Å. These structures confirm the family’s extremely rare dual topology architecture and reveal a cleft between two helices that provides accommodation in the membrane for the hydrophobic substituents of transported drug-like cations.
Hypocretinergic interactions with the serotonergic system regulate REM sleep and cataplexy
Authors: Seifinejad Ali , Li Sha , Possovre Marie-Laure , Vassalli Anne , Tafti Mehdi 
Published: November 2020

AbstractLoss of muscle tone triggered by emotions is called cataplexy and is the pathognomonic symptom of narcolepsy, which is caused by hypocretin deficiency. Cataplexy is classically considered to be an abnormal manifestation of REM sleep and is treated by selective serotonin (5HT) reuptake inhibitors. Here we show that deleting the 5HT transporter in hypocretin knockout mice suppressed cataplexy while dramatically increasing REM sleep. Additionally, double knockout mice showed a significant deficit in the buildup of sleep need. Deleting one allele of the 5HT transporter in hypocretin knockout mice strongly increased EEG theta power during REM sleep and theta and gamma powers during wakefulness. Deleting hypocretin receptors in the dorsal raphe neurons of adult mice did not induce cataplexy but consolidated REM sleep. Our results indicate that cataplexy and REM sleep are regulated by different mechanisms and both states and sleep need are regulated by the hypocretinergic input into 5HT neurons.
Quantification of purified endogenous miRNAs with high sensitivity and specificity
Authors: Shin Soochul , Jung Yoonseok , Uhm Heesoo , Song Minseok , Son Soomin , Goo Jiyoung , Jeong Cherlhyun , Song Ji-Joon , Kim V. Narry , Hohng Sungchul 
Published: November 2020

AbstractMicroRNAs (miRNAs) are short (19–24 nt) non-coding RNAs that suppress the expression of protein coding genes at the post-transcriptional level. Differential expression profiles of miRNAs across a range of diseases have emerged as powerful biomarkers, making a reliable yet rapid profiling technique for miRNAs potentially essential in clinics. Here, we report an amplification-free multi-color single-molecule imaging technique that can profile purified endogenous miRNAs with high sensitivity, specificity, and reliability. Compared to previously reported techniques, our technique can discriminate single base mismatches and single-nucleotide 3′-tailing with low false positive rates regardless of their positions on miRNA. By preloading probes in Thermus thermophilus Argonaute (TtAgo), miRNAs detection speed is accelerated by more than 20 times. Finally, by utilizing the well-conserved linearity between single-molecule spot numbers and the target miRNA concentrations, the absolute average copy numbers of endogenous miRNA species in a single cell can be estimated. Thus our technique, Ago-FISH (Argonaute-based Fluorescence In Situ Hybridization), provides a reliable way to accurately profile various endogenous miRNAs on a single miRNA sensing chip.
High frequency atomic tunneling yields ultralow and glass-like thermal conductivity in chalcogenide single crystals
Authors: Sun Bo , Niu Shanyuan , Hermann Raphael P. , Moon Jaeyun , Shulumba Nina , Page Katharine , Zhao Boyang , Thind Arashdeep S. , Mahalingam Krishnamurthy , Milam-Guerrero JoAnna , Haiges Ralf , Mecklenburg Matthew , Melot Brent C. , Jho Young-Dahl , Howe Brandon M. , Mishra Rohan , Alatas Ahmet , Winn Barry , Manley Michael E. , Ravichandran Jayakanth , Minnich Austin J. 
Published: November 2020

AbstractCrystalline solids exhibiting glass-like thermal conductivity have attracted substantial attention both for fundamental interest and applications such as thermoelectrics. In most crystals, the competition of phonon scattering by anharmonic interactions and crystalline imperfections leads to a non-monotonic trend of thermal conductivity with temperature. Defect-free crystals that exhibit the glassy trend of low thermal conductivity with a monotonic increase with temperature are desirable because they are intrinsically thermally insulating while retaining useful properties of perfect crystals. However, this behavior is rare, and its microscopic origin remains unclear. Here, we report the observation of ultralow and glass-like thermal conductivity in a hexagonal perovskite chalcogenide single crystal, BaTiS3, despite its highly symmetric and simple primitive cell. Elastic and inelastic scattering measurements reveal the quantum mechanical origin of this unusual trend. A two-level atomic tunneling system exists in a shallow double-well potential of the Ti atom and is of sufficiently high frequency to scatter heat-carrying phonons up to room temperature. While atomic tunneling has been invoked to explain the low-temperature thermal conductivity of solids for decades, our study establishes the presence of sub-THz frequency tunneling systems even in high-quality, electrically insulating single crystals, leading to anomalous transport properties well above cryogenic temperatures.
Trans- and cis-acting effects of Firre on epigenetic features of the inactive X chromosome
Authors: Fang He , Bonora Giancarlo , Lewandowski Jordan P. , Thakur Jitendra , Filippova Galina N. , Henikoff Steven , Shendure Jay , Duan Zhijun , Rinn John L. , Deng Xinxian , Noble William S. , Disteche Christine M. 
Published: November 2020

AbstractFirre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26 Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.
An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo
Authors: Vallese Francesca , Catoni Cristina , Cieri Domenico , Barazzuol Lucia , Ramirez Omar , Calore Valentina , Bonora Massimo , Giamogante Flavia , Pinton Paolo , Brini Marisa , Calì Tito 
Published: November 2020

AbstractMembrane contact sites between virtually any known organelle have been documented and, in the last decades, their study received momentum due to their importance for fundamental activities of the cell and for the subtle comprehension of many human diseases. The lack of tools to finely image inter-organelle proximity hindered our understanding on how these subcellular communication hubs mediate and regulate cell homeostasis. We develop an improved and expanded palette of split-GFP-based contact site sensors (SPLICS) for the detection of single and multiple organelle contact sites within a scalable distance range. We demonstrate their flexibility under physiological conditions and in living organisms.
A mechanically adaptive hydrogel with a reconfigurable network consisting entirely of inorganic nanosheets and water
Authors: Sano Koki , Igarashi Naoki , Ebina Yasuo , Sasaki Takayoshi , Hikima Takaaki , Aida Takuzo , Ishida Yasuhiro 
Published: November 2020

AbstractAlthough various biomimetic soft materials that display structural hierarchies and stimuli responsiveness have been developed from organic materials, the creation of their counterparts consisting entirely of inorganic materials presents an attractive challenge, as the properties of such materials generally differ from those of living organisms. Here, we have developed a hydrogel consisting of inorganic nanosheets (14 wt%) and water (86 wt%) that undergoes thermally induced reversible and abrupt changes in its internal structure and mechanical elasticity (23-fold). At room temperature, the nanosheets in water electrostatically repel one another and self-assemble into a long-periodic lamellar architecture with mutually restricted mobility, forming a physical hydrogel. Upon heating above 55 °C, the electrostatic repulsion is overcome by competing van der Waals attraction, and the nanosheets rearrange into an interconnected 3D network of another hydrogel. By doping the gel with a photothermal-conversion agent, the gel-to-gel transition becomes operable spatiotemporally on photoirradiation.
Single particle tunneling spectrum of superconducting Nd1-xSrxNiO2 thin films
Authors: Gu Qiangqiang , Li Yueying , Wan Siyuan , Li Huazhou , Guo Wei , Yang Huan , Li Qing , Zhu Xiyu , Pan Xiaoqing , Nie Yuefeng , Wen Hai-Hu 
Published: November 2020

AbstractThe pairing mechanism in cuprates remains as one of the most challenging issues in condensed matter physics. Recently, superconductivity was discovered in thin films of the infinite-layer nickelate Nd1-xSrxNiO2 (x = 0.12–0.25) which is believed to have the similar 3d9 orbital electrons as that in cuprates. Here we report single-particle tunneling measurements on the superconducting nickelate thin films. We find predominantly two types of tunneling spectra, one shows a V-shape feature which can be fitted well by a d-wave gap function with gap maximum of about 3.9 meV, another one exhibits a full gap of about 2.35 meV. Some spectra demonstrate mixed contributions of these two components. Combining with theoretical calculations, we attribute the d-wave gap to the pairing potential of the $${\mathrm{Ni - }}3d_{x^2 - y^2}$$
Ni-
3

d

x

2

−

y

2

orbital. Several possible reasons are given for explaining the full gap feature. Our results indicate both similarities and distinctions between the newly found Ni-based superconductors and cuprates.
Tunable analog thermal material
Authors: Xu Guoqiang , Dong Kaichen , Li Ying , Li Huagen , Liu Kaipeng , Li Longqiu , Wu Junqiao , Qiu Cheng-Wei 
Published: November 2020

AbstractNaturally-occurring thermal materials usually possess specific thermal conductivity (κ), forming a digital set of κ values. Emerging thermal metamaterials have been deployed to realize effective thermal conductivities unattainable in natural materials. However, the effective thermal conductivities of such mixing-based thermal metamaterials are still in digital fashion, i.e., the effective conductivity remains discrete and static. Here, we report an analog thermal material whose effective conductivity can be in-situ tuned from near-zero to near-infinity κ. The proof-of-concept scheme consists of a spinning core made of uncured polydimethylsiloxane (PDMS) and fixed bilayer rings made of silicone grease and steel. Thanks to the spinning PDMS and its induced convective effects, we can mold the heat flow robustly with continuously changing and anisotropic κ. Our work enables a single functional thermal material to meet the challenging demands of flexible thermal manipulation. It also provides platforms to investigate heat transfer in systems with moving components.
Analysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry
Authors: Qiu Danye , Wilson Miranda S. , Eisenbeis Verena B. , Harmel Robert K. , Riemer Esther , Haas Thomas M. , Wittwer Christopher , Jork Nikolaus , Gu Chunfang , Shears Stephen B. , Schaaf Gabriel , Kammerer Bernd , Fiedler Dorothea , Saiardi Adolfo , Jessen Henning J. 
Published: November 2020

AbstractThe analysis of myo-inositol phosphates (InsPs) and myo-inositol pyrophosphates (PP-InsPs) is a daunting challenge due to the large number of possible isomers, the absence of a chromophore, the high charge density, the low abundance, and the instability of the esters and anhydrides. Given their importance in biology, an analytical approach to follow and understand this complex signaling hub is desirable. Here, capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (ESI-MS) is implemented to analyze complex mixtures of InsPs and PP-InsPs with high sensitivity. Stable isotope labeled (SIL) internal standards allow for matrix-independent quantitative assignment. The method is validated in wild-type and knockout mammalian cell lines and in model organisms. SIL-CE-ESI-MS enables the accurate monitoring of InsPs and PP-InsPs arising from compartmentalized cellular synthesis pathways, by feeding cells with either [13C6]-myo-inositol or [13C6]-D-glucose. In doing so, we provide evidence for the existence of unknown inositol synthesis pathways in mammals, highlighting the potential of this method to dissect inositol phosphate metabolism and signalling.
Direct observation of large electron–phonon interaction effect on phonon heat transport
Authors: Zhou Jiawei , Shin Hyun D. , Chen Ke , Song Bai , Duncan Ryan A. , Xu Qian , Maznev Alexei A. , Nelson Keith A. , Chen Gang 
Published: November 2020

AbstractAs a foundational concept in many-body physics, electron–phonon interaction is essential to understanding and manipulating charge and energy flow in various electronic, photonic, and energy conversion devices. While much progress has been made in uncovering how phonons affect electron dynamics, it remains a challenge to directly observe the impact of electrons on phonon transport, especially at environmental temperatures. Here, we probe the effect of charge carriers on phonon heat transport at room temperature, using a modified transient thermal grating technique. By optically exciting electron-hole pairs in a crystalline silicon membrane, we single out the effect of the phonon–carrier interaction. The enhanced phonon scattering by photoexcited free carriers results in a substantial reduction in thermal conductivity on a nanosecond timescale. Our study provides direct experimental evidence of the elusive role of electron–phonon interaction in phonon heat transport, which is important for understanding heat conduction in doped semiconductors. We also highlight the possibility of using light to dynamically control thermal transport via electron–phonon coupling.