bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interfering with retrotransposition by two types of CRISPR effectors: Cas12a and Cas13a
Authors: Zhang Niubing , Jing Xinyun , Liu Yuanhua , Chen Minjie , Zhu Xianfeng , Jiang Jing , Wang Hongbing , Li Xuan , Hao Pei 
Published: May 2020

AbstractCRISPRs are a promising tool being explored in combating exogenous retroviral pathogens and in disabling endogenous retroviruses for organ transplantation. The Cas12a and Cas13a systems offer novel mechanisms of CRISPR actions that have not been evaluated for retrovirus interference. Particularly, a latest study revealed that the activated Cas13a provided bacterial hosts with a “passive protection” mechanism to defend against DNA phage infection by inducing cell growth arrest in infected cells, which is especially significant as it endows Cas13a, a RNA-targeting CRISPR effector, with mount defense against both RNA and DNA invaders. Here, by refitting long terminal repeat retrotransposon Tf1 as a model system, which shares common features with retrovirus regarding their replication mechanism and life cycle, we repurposed CRISPR-Cas12a and -Cas13a to interfere with Tf1 retrotransposition, and evaluated their different mechanisms of action. Cas12a exhibited strong inhibition on retrotransposition, allowing marginal Tf1 transposition that was likely the result of a lasting pool of Tf1 RNA/cDNA intermediates protected within virus-like particles. The residual activities, however, were completely eliminated with new constructs for persistent crRNA targeting. On the other hand, targeting Cas13a to Tf1 RNA intermediates significantly inhibited Tf1 retrotransposition. However, unlike in bacterial hosts, the sustained activation of Cas13a by Tf1 transcripts did not cause cell growth arrest in S. pombe, indicating that virus-activated Cas13a likely acted differently in eukaryotic cells. The study gained insight into the actions of novel CRISPR mechanisms in combating retroviral pathogens, and established system parameters for developing new strategies in treatment of retrovirus-related diseases.
Extinction of eastern Sahul megafauna coincides with sustained environmental deterioration
Authors: Hocknull Scott A. , Lewis Richard , Arnold Lee J. , Pietsch Tim , Joannes-Boyau Renaud , Price Gilbert J. , Moss Patrick , Wood Rachel , Dosseto Anthony , Louys Julien , Olley Jon , Lawrence Rochelle A. 
Published: May 2020

AbstractExplanations for the Upper Pleistocene extinction of megafauna from Sahul (Australia and New Guinea) remain unresolved. Extinction hypotheses have advanced climate or human-driven scenarios, in spite of over three quarters of Sahul lacking reliable biogeographic or chronologic data. Here we present new megafauna from north-eastern Australia that suffered extinction sometime after 40,100 (±1700) years ago. Megafauna fossils preserved alongside leaves, seeds, pollen and insects, indicate a sclerophyllous forest with heathy understorey that was home to aquatic and terrestrial carnivorous reptiles and megaherbivores, including the world’s largest kangaroo. Megafauna species diversity is greater compared to southern sites of similar age, which is contrary to expectations if extinctions followed proposed migration routes for people across Sahul. Our results do not support rapid or synchronous human-mediated continental-wide extinction, or the proposed timing of peak extinction events. Instead, megafauna extinctions coincide with regionally staggered spatio-temporal deterioration in hydroclimate coupled with sustained environmental change.
Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice
Authors: Srifa Waracharee , Kosaric Nina , Amorin Alvaro , Jadi Othmane , Park Yujin , Mantri Sruthi , Camarena Joab , Gurtner Geoffrey C. , Porteus Matthew 
Published: May 2020

AbstractHuman mesenchymal stromal cells (hMSCs) are a promising source for engineered cell-based therapies in which genetic engineering could enhance therapeutic efficacy and install novel cellular functions. Here, we describe an optimized Cas9-AAV6-based genome editing tool platform for site-specific mutagenesis and integration of up to more than 3 kilobases of exogenous DNA in the genome of hMSCs derived from the bone marrow, adipose tissue, and umbilical cord blood without altering their ex vivo characteristics. We generate safe harbor-integrated lines of engineered hMSCs and show that engineered luciferase-expressing hMSCs are transiently active in vivo in wound beds of db/db mice. Moreover, we generate PDGF-BB- and VEGFA-hypersecreting hMSC lines as short-term, local wound healing agents with superior therapeutic efficacy over wildtype hMSCs in the diabetic mouse model without replacing resident cells long-term. This study establishes a precise genetic engineering platform for genetic studies of hMSCs and development of engineered hMSC-based therapies.
Representing the function and sensitivity of coastal interfaces in Earth system models
Authors: Ward Nicholas D. , Megonigal J. Patrick , Bond-Lamberty Ben , Bailey Vanessa L. , Butman David , Canuel Elizabeth A. , Diefenderfer Heida , Ganju Neil K. , Goñi Miguel A. , Graham Emily B. , Hopkinson Charles S. , Khangaonkar Tarang , Langley J. Adam , McDowell Nate G. , Myers-Pigg Allison N. , Neumann Rebecca B. , Osburn Christopher L. , Price René M. , Rowland Joel , Sengupta Aditi , Simard Marc , Thornton Peter E. , Tzortziou Maria , Vargas Rodrigo , Weisenhorn Pamela B. , Windham-Myers Lisamarie 
Published: May 2020

AbstractBetween the land and ocean, diverse coastal ecosystems transform, store, and transport material. Across these interfaces, the dynamic exchange of energy and matter is driven by hydrological and hydrodynamic processes such as river and groundwater discharge, tides, waves, and storms. These dynamics regulate ecosystem functions and Earth’s climate, yet global models lack representation of coastal processes and related feedbacks, impeding their predictions of coastal and global responses to change. Here, we assess existing coastal monitoring networks and regional models, existing challenges in these efforts, and recommend a path towards development of global models that more robustly reflect the coastal interface.
Nature of power electronics and integration of power conversion with communication for talkative power
Authors: He Xiangning , Wang Ruichi , Wu Jiande , Li Wuhua 
Published: May 2020

AbstractPower electronics and communication electronics are both based on electromagnetic theory, but they are usually regarded as two distinct subfields in electrical engineering. In fact, however, electric power is the most common matter-based carrier of messages; thus, power electronics and communications can be jointly considered. Here we study the essential nature of dc-dc power converters and characterize the similarity of their operation principle to that of communication systems. Based on this similarity and the double modulation methods used in power electronics and communication, a double modulation strategy for both power and data is presented and applied in dc-dc power converters to achieve what we call ‘talkative power’. A modulation strategy called frequency hopping-differential phase shift keying (FH-DPSK) is also presented to overcome the crosstalk between chosen transmission systems. The proposed talkative power strategy sheds new light on and provides inspiration for the further development of power electronics and communication.
Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels
Authors: Johnson Elizabeth L. , Heaver Stacey L. , Waters Jillian L. , Kim Benjamin I. , Bretin Alexis , Goodman Andrew L. , Gewirtz Andrew T. , Worgall Tilla S. , Ley Ruth E. 
Published: May 2020

AbstractGut microbes are linked to host metabolism, but specific mechanisms remain to be uncovered. Ceramides, a type of sphingolipid (SL), have been implicated in the development of a range of metabolic disorders from insulin resistance (IR) to hepatic steatosis. SLs are obtained from the diet and generated by de novo synthesis in mammalian tissues. Another potential, but unexplored, source of mammalian SLs is production by Bacteroidetes, the dominant phylum of the gut microbiome. Genomes of Bacteroides spp. and their relatives encode serine palmitoyltransfease (SPT), allowing them to produce SLs. Here, we explore the contribution of SL-production by gut Bacteroides to host SL homeostasis. In human cell culture, bacterial SLs are processed by host SL-metabolic pathways. In mouse models, Bacteroides-derived lipids transfer to host epithelial tissue and the hepatic portal vein. Administration of B. thetaiotaomicron to mice, but not an SPT-deficient strain, reduces de novo SL production and increases liver ceramides. These results indicate that gut-derived bacterial SLs affect host lipid metabolism.
Large-scale electron microscopy database for human type 1 diabetes
Authors: de Boer Pascal , Pirozzi Nicole M. , Wolters Anouk H. G. , Kuipers Jeroen , Kusmartseva Irina , Atkinson Mark A. , Campbell-Thompson Martha , Giepmans Ben N. G. 
Published: May 2020

AbstractAutoimmune β-cell destruction leads to type 1 diabetes, but the pathophysiological mechanisms remain unclear. To help address this void, we created an open-access online repository, unprecedented in its size, composed of large-scale electron microscopy images (‘nanotomy’) of human pancreas tissue obtained from the Network for Pancreatic Organ donors with Diabetes (nPOD; www.nanotomy.org). Nanotomy allows analyses of complete donor islets with up to macromolecular resolution. Anomalies we found in type 1 diabetes included (i) an increase of ‘intermediate cells’ containing granules resembling those of exocrine zymogen and endocrine hormone secreting cells; and (ii) elevated presence of innate immune cells. These are our first results of mining the database and support recent findings that suggest that type 1 diabetes includes abnormalities in the exocrine pancreas that may induce endocrine cellular stress as a trigger for autoimmunity.
Switching of band inversion and topological surface states by charge density wave
Authors: Mitsuishi N. , Sugita Y. , Bahramy M. S. , Kamitani M. , Sonobe T. , Sakano M. , Shimojima T. , Takahashi H. , Sakai H. , Horiba K. , Kumigashira H. , Taguchi K. , Miyamoto K. , Okuda T. , Ishiwata S. , Motome Y. , Ishizaka K. 
Published: May 2020

AbstractTopologically nontrivial materials host protected edge states associated with the bulk band inversion through the bulk-edge correspondence. Manipulating such edge states is highly desired for developing new functions and devices practically using their dissipation-less nature and spin-momentum locking. Here we introduce a transition-metal dichalcogenide VTe2, that hosts a charge density wave (CDW) coupled with the band inversion involving V3d and Te5p orbitals. Spin- and angle-resolved photoemission spectroscopy with first-principles calculations reveal the huge anisotropic modification of the bulk electronic structure by the CDW formation, accompanying the selective disappearance of Dirac-type spin-polarized topological surface states that exist in the normal state. Thorough three dimensional investigation of bulk states indicates that the corresponding band inversion at the Brillouin zone boundary dissolves upon the CDW formation, by transforming into anomalous flat bands. Our finding provides a new insight to the topological manipulation of matters by utilizing CDWs’ flexible characters to external stimuli.
Manipulating the fluorescence lifetime at the sub-cellular scale via photo-switchable barcoding
Authors: Xie Yujie , Arno Maria C. , Husband Jonathan T. , Torrent-Sucarrat Miquel , O’Reilly Rachel K. 
Published: May 2020

AbstractFluorescent barcoding is a pivotal technique for the investigation of the microscale world, from information storage to the monitoring of dynamic biochemical processes. Using fluorescence lifetime as the readout modality offers more reproducible and quantitative outputs compared to conventional fluorescent barcoding, being independent of sample concentration and measurement methods. However, the use of fluorescence lifetime in this area has been limited by the lack of strategies that provide spatiotemporal manipulation of the coding process. In this study, we design a two-component photo-switchable nanogel that exhibits variable fluorescence lifetime upon photoisomerization-induced energy transfer processes through light irradiation. This remotely manipulated fluorescence lifetime property could be visually mapped using fluorescence lifetime imaging microscopy (FLIM), allowing selective storage and display of information at the microscale. Most importantly, the reversibility of this system further provides a strategy for minimizing the background influence in fluorescence lifetime imaging of live cells and sub-cellular organelles.
TFEB regulates murine liver cell fate during development and regeneration
Authors: Pastore Nunzia , Huynh Tuong , Herz Niculin J. , Calcagni’ Alessia , Klisch Tiemo J. , Brunetti Lorenzo , Kim Kangho Ho , De Giorgi Marco , Hurley Ayrea , Carissimo Annamaria , Mutarelli Margherita , Aleksieva Niya , D’Orsi Luca , Lagor William R. , Moore David D. , Settembre Carmine , Finegold Milton J. , Forbes Stuart J. , Ballabio Andrea 
Published: May 2020

AbstractIt is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show thatSox9, a marker of precursor and biliary cells, is a direct transcriptional target of TFEB and a primary mediator of its effects on liver cell fate. In summary, our findings identify an unexplored pathway that controls liver cell lineage commitment and whose dysregulation may play a role in biliary cancer.
Ecological drivers of global gradients in avian dispersal inferred from wing morphology
Authors: Sheard Catherine , Neate-Clegg Montague H. C. , Alioravainen Nico , Jones Samuel E. I. , Vincent Claire , MacGregor Hannah E. A. , Bregman Tom P. , Claramunt Santiago , Tobias Joseph A. 
Published: May 2020

AbstractAn organism’s ability to disperse influences many fundamental processes, from speciation and geographical range expansion to community assembly. However, the patterns and underlying drivers of variation in dispersal across species remain unclear, partly because standardised estimates of dispersal ability are rarely available. Here we present a global dataset of avian hand-wing index (HWI), an estimate of wing shape widely adopted as a proxy for dispersal ability in birds. We show that HWI is correlated with geography and ecology across 10,338 (>99%) species, increasing at higher latitudes and with migration, and decreasing with territoriality. After controlling for these effects, the strongest predictor of HWI is temperature variability (seasonality), with secondary effects of diet and habitat type. Finally, we also show that HWI is a strong predictor of geographical range size. Our analyses reveal a prominent latitudinal gradient in HWI shaped by a combination of environmental and behavioural factors, and also provide a global index of avian dispersal ability for use in community ecology, macroecology, and macroevolution.
Low-temperature spin dynamics of ferromagnetic molecular ring {Cr8Y8}
Authors: Fu Zhendong , Qin Lei , Sun Kai , Hao Lijie , Zheng Yan-Zhen , Lohstroh Wiebke , Günther Gerrit , Russina Margarita , Liu Yuntao , Xiao Yinguo , Jin Wentao , Chen Dongfeng 
Published: May 2020

AbstractThe spin dynamics of {Cr8Y8}, a rare example of ferromagnetic molecular rings, has been studied by inelastic neutron scattering (INS) and heat capacity (HC) methods. Clear evidence of low-lying magnetic excitation has been found. Magnetic Schottky anomalies are observed in low-temperature (low-T) HC curves measured under various fields and can be well fitted with a multi-level Schottky term, giving important information on the energy gaps between spin levels. The INS results obtained on TOFTOF and NEAT time-of-flight spectrometers show INS peaks corresponding to the transitions within S = 12 ground states and between the S = 12 ground state and the S = 11 excited state. The single-J model with a unique exchange constant J = 0.151 meV can well reproduce the low-lying energy levels and their Zeeman splitting upon applied magnetic fields. This work shows that the single-J model can be a good approach for the low-T spin dynamics of {Cr8Y8} and may have general significance for other weak ferromagnetic molecular rings. Determination of the Cr3+-Cr3+ exchange constant in {Cr8Y8} will benefit the study on the complicated magnetic interactions in chromium lanthanide complexes. The zero-field splitting which is suggested by HC data still calls for EPR or high-resolution INS technique to verify.
Using the force: STEM knowledge and experience construct shared neural representations of engineering concepts
Authors: Cetron Joshua S. , Connolly Andrew C. , Diamond Solomon G. , May Vicki V. , Haxby James V. , Kraemer David J. M. 
Published: May 2020

AbstractHow does STEM knowledge learned in school change students’ brains? Using fMRI, we presented photographs of real-world structures to engineering students with classroom-based knowledge and hands-on lab experience, examining how their brain activity differentiated them from their “novice” peers not pursuing engineering degrees. A data-driven MVPA and machine-learning approach revealed that neural response patterns of engineering students were convergent with each other and distinct from novices’ when considering physical forces acting on the structures. Furthermore, informational network analysis demonstrated that the distinct neural response patterns of engineering students reflected relevant concept knowledge: learned categories of mechanical structures. Information about mechanical categories was predominantly represented in bilateral anterior ventral occipitotemporal regions. Importantly, mechanical categories were not explicitly referenced in the experiment, nor does visual similarity between stimuli account for mechanical category distinctions. The results demonstrate how learning abstract STEM concepts in the classroom influences neural representations of objects in the world.
Identifying inhibitors of epithelial–mesenchymal plasticity using a network topology-based approach
Authors: Hari Kishore , Sabuwala Burhanuddin , Subramani Balaram Vishnu , La Porta Caterina A. M. , Zapperi Stefano , Font-Clos Francesc , Jolly Mohit Kumar 
Published: May 2020

AbstractMetastasis is the cause of over 90% of cancer-related deaths. Cancer cells undergoing metastasis can switch dynamically between different phenotypes, enabling them to adapt to harsh challenges, such as overcoming anoikis and evading immune response. This ability, known as phenotypic plasticity, is crucial for the survival of cancer cells during metastasis, as well as acquiring therapy resistance. Various biochemical networks have been identified to contribute to phenotypic plasticity, but how plasticity emerges from the dynamics of these networks remains elusive. Here, we investigated the dynamics of various regulatory networks implicated in Epithelial–mesenchymal plasticity (EMP)—an important arm of phenotypic plasticity—through two different mathematical modelling frameworks: a discrete, parameter-independent framework (Boolean) and a continuous, parameter-agnostic modelling framework (RACIPE). Results from either framework in terms of phenotypic distributions obtained from a given EMP network are qualitatively similar and suggest that these networks are multi-stable and can give rise to phenotypic plasticity. Neither method requires specific kinetic parameters, thus our results emphasize that EMP can emerge through these networks over a wide range of parameter sets, elucidating the importance of network topology in enabling phenotypic plasticity. Furthermore, we show that the ability to exhibit phenotypic plasticity correlates positively with the number of positive feedback loops in a given network. These results pave a way toward an unorthodox network topology-based approach to identify crucial links in a given EMP network that can reduce phenotypic plasticity and possibly inhibit metastasis—by reducing the number of positive feedback loops.
Compound Opening Arrow Mixture exerts anti-tumor effects in a mouse model of breast cancer
Authors: Zhou Zhen , Peng Yanfang , Ai Wang , Li Qi , Ye Taisheng , Wu Chaoyan , Ke Haoliang , Wang Xiuping , Zhang Yingwen 
Published: May 2020

AbstractCompound Opening Arrow Mixture (COAM) has demonstrated therapeutic effects in patients with breast cancer. We explored the underlying molecular mechanisms of COAM using a mouse model of breast cancer. Luciferase-labeled 4T1-Luc2 cells were inoculated into the breast pad of BALB/c-nu mice, which were divided into model group (saline), COAM (6 g/ml high-dose, 3 g/ml medium-dose, and 1.5 g/ml low-dose) groups, and low-molecular-weight heparin (LMWH, 1500 U/Kg) group. The number and distribution of 4T1-luc2 tumors were measured by an in vivo imaging system. Tumor cell apoptosis was measured through TUNEL and quantitating the expression of Caspase-3 mRNA and protein. Compared with the model group, in vivo tumor growth was lower in the LMWH- and COAM-treated groups. Tumor apoptosis was time-dependent and dose-dependent, as shown by a higher TUNEL apoptotic index and higher Caspase-3 mRNA and Caspase-3/cleaved-Caspase-3 proteins levels on the 14th day than the 7th day. The COAM high-dose group had the highest apoptotic index and the most activation of Caspase-3. Collectively, COAM significantly inhibits the growth of 4T1-luc2 breast cancer in mice and induces tumor apoptosis by activating Caspase-3, which provides a preliminary explanation of therapeutic effects of COAM.
Slip rates along the narrow Magallanes Fault System, Tierra Del Fuego Region, Patagonia
Authors: Sandoval Francisca B. , De Pascale Gregory P. 
Published: May 2020

AbstractThe up to 1000 km-long Magallanes Fault System (MFS) is the southernmost onshore strike-slip plate boundary and located between the South American and Scotia Plates. Slip-rates, a key factor for understanding neotectonics and seismic hazard are only available there from geodetic models. In this study, we present the first direct geologic evidence of MFS slip rates. Late-Cenozoic slip rates along the main MF is 5.4 ± 3.3 mm/yr based on lithologic geological separations found in regional mapping. Late-Quaternary deformation from offset geomorphologic markers was documented along the MFS in Chile and Argentina based on a combination of satellite mapping, fieldwork, and Structure from Motion (SfM) models developed from drone photography. By combining displacements observed in SfM models with regional Late-Quaternary dating, sinistral slip rates are 10.5 ± 1.5 mm/yr (Chile) and 7.8 ± 1.3 mm/yr (Argentina). By comparing our results with regional models, contemporary plate boundary deformation is narrow, approximately ~20–50 km wide from Tierra Del Fuego (TdF) and east (one of the narrowest on Earth), which widens and becoming more diffuse from Cabo Froward north and west (>100 km wide). In addition to the tectonic implications, these faults should be considered important sources of fault rupture and seismic hazard.