bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coseismic Underground Rupture, Geometry, Historical Surface Deformations, and Seismic Potentials of the 28 March 2019 Mw 5.04 Mangya Earthquake Fault
Authors: Wang Shengli , Wu Wujun , Li Qinghong , Li Chao , Li Yongxiang , Chen Yan , Wang Liangshu , Xu Mingjie , Guo Zhi 
Published: October 2020

AbstractThe 28 March 2019 Mw 5.04 Mangya earthquake damaged eight ongoing drilling boreholes in the oil‐production Yingxiong Ling (YXL) area, southwestern Qaidam of northern Tibet. The borehole damages provide an opportunity to measure directly the coseismic slips, the rupture area, and the seismic moment. The damages reveal the underground rupture area of 45.30 ± 10.24 km2, the maximum slip of 400 ± 13 mm, and the seismogenic fault dip of ~38.6°. These parameters generate a seismic moment of (1.81 ± 0.47) × 1017 Nm and a moment magnitude of 5.47 ± 0.16. Seismic exploration reveals that the geometry of the SZG ramp, the uppermost part of the multibend Yingxiong Ling thrust system, agrees primarily with the rupture plane derived from the borehole damages and one plane of the focal mechanism solution. This suggests that this earthquake resulted from slipping on the ramp. The hanging wall of the YXL thrust system forms the complex fault‐bend fold YXL anticlinorium. Active thrusting and folding along both edges of YXL attest to the southwestern vergence of this thrust system. Growth strata demonstrate average slip rates of the thrust system ranging from ~0.2 to ~0.3 mm/yr. The thrusted and folded recent alluviums along the southwestern edge indicate two thrusting events with coseismic slips of 1.7 ± 0.15 and 3.5 ± 0.15 m at 6.16 ± 0.52 and ~35.91 ka, respectively. The entire rupturing of the thrust system can produce Mw 7.65 ± 0.03 earthquakes.
B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation
Authors: Giagulli Cinzia , Caccuri Francesca , Zorzan Simone , Bugatti Antonella , Zani Alberto , Filippini Federica , Manocha Ekta , D’Ursi Pasqualina , Orro Alessandro , Dolcetti Riccardo , Caruso Arnaldo 
Published: October 2020

AbstractCombined antiretroviral therapy (cART) for HIV-1 dramatically slows disease progression among HIV+individuals. Currently, lymphoma represents the main cause of death among HIV-1-infected patients. Detection of p17 variants (vp17s) endowed with B-cell clonogenic activity in HIV-1-seropositive patients with lymphoma suggests their possible role in lymphomagenesis. Here, we demonstrate that the clonogenic activity of vp17s is mediated by their binding to PAR1 and to PAR1-mediated EGFR transactivation through Gq protein. The entire vp17s-triggered clonogenic process is MMPs dependent. Moreover, phosphoproteomic and bioinformatic analysis highlighted the crucial role of EGFR/PI3K/Akt pathway in modulating several molecules promoting cancer progression, including RAC1, ABL1, p53, CDK1, NPM, Rb, PTP-1B, and STAT1. Finally, we show that a peptide (F1) corresponding to the vp17s functional epitope is sufficient to trigger the PAR1/EGFR/PI3K/Akt pathway and bind PAR1. Our findings suggest novel potential therapeutic targets to counteract vp17-driven lymphomagenesis in HIV+patients.
Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity
Authors: Wang Ming , Cai Yang , Peng Yong , Xu Bo , Hui Wentao , Jiang Yugang 
Published: October 2020

AbstractGlioblastoma multiforme (GBM) is highly invasive, with a high recurrence rate and limited treatment options, and is the deadliest glioma. Exosomes (Exos) have attracted much attention in the diagnosis and treatment of GBM and are expected to address the severe limitations of biopsy conditions. Exos in the cerebrospinal fluid (CSF) have great potential in GBM dynamic monitoring and intervention strategies. Here, we evaluated the difference in the proteome information of Exos from the CSF (CSF-Exos) between GBM patients and low-grade glioma patients, and the correlations between GBM-CSF-Exos and immunosuppressive properties. Our results indicates that GBM-CSF-Exos contained a unique protein, LGALS9 ligand, which bound to the TIM3 receptor of dendritic cells (DCs) in the CSF to inhibit antigen recognition, processing and presentation by DCs, leading to failure of the cytotoxic T-cell-mediated antitumor immune response. Blocking the secretion of exosomal LGALS9 from GBM tumors could cause mice to exhibit sustained DC tumor antigen-presenting activity and long-lasting antitumor immunity. We concluded that GBM cell-derived exosomal LGALS9 acts as a major regulator of tumor progression by inhibiting DC antigen presentation and cytotoxic T-cell activation in the CSF and that loss of this inhibitory effect can lead to durable systemic antitumor immunity.
Functional validation of a human GLUD2 variant in a murine model of Parkinson’s disease
Authors: Zhang Wenlong , Gong Junwei , Ding Liuyan , Zhang Zhiling , Pan Xiaowen , Chen Xiang , Guo Wenyuan , Zhang Xiaokang , Yang Xinling , Peng Guoyou , Lin Yuwan , Gao Feng , Li Yuanquan , Zhu Xiaoqin , Xuan Aiguo , Wang Shu , Sun Xiangdong , Zhang Yunlong , Xu Pingyi 
Published: October 2020

AbstractParkinson’s disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.
RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/β-catenin signaling pathway
Authors: Sun Jikui , Ma Quanfeng , Li Banban , Wang Chen , Mo Lidong , Zhang Xuebin , Tang Fan , Wang Qiong , Yan Xiaoling , Yao Xiuhua , Wu Qiaoli , Shu Chang , Xiong Jinbiao , Fan Weijia , Wang Jinhuan 
Published: October 2020

AbstractAccumulating evidence indicates that the dysregulation of the miRNAs/mRNA-mediated carcinogenic signaling pathway network is intimately involved in glioma initiation and progression. In the present study, by performing experiments and bioinformatics analysis, we found that RPN2 was markedly elevated in glioma specimens compared with normal controls, and its upregulation was significantly linked to WHO grade and poor prognosis. Knockdown of RPN2 inhibited tumor proliferation and invasion, promoted apoptosis, and enhanced temozolomide (TMZ) sensitivity in vitro and in vivo. Mechanistic investigation revealed that RPN2 deletion repressed β-catenin/Tcf-4 transcription activity partly through functional activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, we showed that RPN2 is a direct functional target of miR-181c. Ectopic miR-181c expression suppressed β-catenin/Tcf-4 activity, while restoration of RPN2 partly reversed this inhibitory effect mediated by miR-181c, implying a molecular mechanism in which TMZ sensitivity is mediated by miR-181c. Taken together, our data revealed a new miR-181c/RPN2/wnt/β-catenin signaling axis that plays significant roles in glioma tumorigenesis and TMZ resistance, and it represents a potential therapeutic target, especially in GBM.
BET degrader inhibits tumor progression and stem-like cell growth via Wnt/β-catenin signaling repression in glioma cells
Authors: Tian Tao , Guo Tongqi , Zhen Wei , Zou Jianjun , Li Fuyong 
Published: October 2020

AbstractBased on their histological appearance, gliomas are a very common primary tumor type of the brain and are classified into grades, Grade I to Grade IV, of the World Health Organization. Treatment failure is due to the cancer stem cells (CSC) phenotype maintenance and self-renewal. BET degraders such as ZBC260 represents a novel class of BET inhibitors that act by inducing BET proteins degradation. This study explores the mode of action and effects of ZBC260 in vivo and in vitro against glioma. By inhibiting cell proliferation and inducting cell cycle arrest, the fact that glioma cell lines show sensitivity to ZBC260. Notably, ZBC260 targeted glioma without side effects in vivo. In addition, the stem cell-like properties of glioma cells were inhibited upon ZBC260 treatment. When the mechanism was examined, our findings indicated that Wnt/β-catenin pathway repression is required for ZBC260-induced stem cell-like properties and tumor growth suppression. In conclusion, the growth of tumors and stem cell-like properties were inhibited by ZBC260 via Wnt/β-catenin repression, which suggests ZBC260 as a potential therapeutic agent for glioma.
MSH1-induced heritable enhanced growth vigor through grafting is associated with the RdDM pathway in plants
Authors: Kundariya Hardik , Yang Xiaodong , Morton Kyla , Sanchez Robersy , Axtell Michael J. , Hutton Samuel F. , Fromm Michael , Mackenzie Sally A. 
Published: October 2020

AbstractPlants transmit signals long distances, as evidenced in grafting experiments that create distinct rootstock-scion junctions. Noncoding small RNA is a signaling molecule that is graft transmissible, participating in RNA-directed DNA methylation; but the meiotic transmissibility of graft-mediated epigenetic changes remains unclear. Here, we exploit the MSH1 system in Arabidopsis and tomato to introduce rootstock epigenetic variation to grafting experiments. Introducing mutations dcl2, dcl3 and dcl4 to the msh1 rootstock disrupts siRNA production and reveals RdDM targets of methylation repatterning. Progeny from grafting experiments show enhanced growth vigor relative to controls. This heritable enhancement-through-grafting phenotype is RdDM-dependent, involving 1380 differentially methylated genes, many within auxin-related gene pathways. Growth vigor is associated with robust root growth of msh1 graft progeny, a phenotype associated with auxin transport based on inhibitor assays. Large-scale field experiments show msh1 grafting effects on tomato plant performance, heritable over five generations, demonstrating the agricultural potential of epigenetic variation.
Reorientation-induced relaxation of free OH at the air/water interface revealed by ultrafast heterodyne-detected nonlinear spectroscopy
Authors: Inoue Ken-ichi , Ahmed Mohammed , Nihonyanagi Satoshi , Tahara Tahei 
Published: October 2020

AbstractThe uniqueness of water originates from its three-dimensional hydrogen-bond network, but this hydrogen-bond network is suddenly truncated at the interface and non-hydrogen-bonded OH (free OH) appears. Although this free OH is the most characteristic feature of interfacial water, the molecular-level understanding of its dynamic property is still limited due to the technical difficulty. We study ultrafast vibrational relaxation dynamics of the free OH at the air/water interface using time-resolved heterodyne-detected vibrational sum frequency generation (TR-HD-VSFG) spectroscopy. With the use of singular value decomposition (SVD) analysis, the vibrational relaxation (T1) times of the free OH at the neat H2O and isotopically-diluted water interfaces are determined to be 0.87 ± 0.06 ps (neat H2O), 0.84 ± 0.09 ps (H2O/HOD/D2O = 1/2/1), and 0.88 ± 0.16 ps (H2O/HOD/D2O = 1/8/16). The absence of the isotope effect on the T1 time indicates that the main mechanism of the vibrational relaxation of the free OH is reorientation of the topmost water molecules. The determined sub-picosecond T1 time also suggests that the free OH reorients diffusively without the switching of the hydrogen-bond partner by the topmost water molecule.
Low cost DNA data storage using photolithographic synthesis and advanced information reconstruction and error correction
Authors: Antkowiak Philipp L. , Lietard Jory , Darestani Mohammad Zalbagi , Somoza Mark M. , Stark Wendelin J. , Heckel Reinhard , Grass Robert N. 
Published: October 2020

AbstractDue to its longevity and enormous information density, DNA is an attractive medium for archival storage. The current hamstring of DNA data storage systems—both in cost and speed—is synthesis. The key idea for breaking this bottleneck pursued in this work is to move beyond the low-error and expensive synthesis employed almost exclusively in today’s systems, towards cheaper, potentially faster, but high-error synthesis technologies. Here, we demonstrate a DNA storage system that relies on massively parallel light-directed synthesis, which is considerably cheaper than conventional solid-phase synthesis. However, this technology has a high sequence error rate when optimized for speed. We demonstrate that even in this high-error regime, reliable storage of information is possible, by developing a pipeline of algorithms for encoding and reconstruction of the information. In our experiments, we store a file containing sheet music of Mozart, and show perfect data recovery from low synthesis fidelity DNA.
Analysis of metabolites and metabolic pathways in three maize (Zea mays L.) varieties from the same origin using GC–MS
Authors: Zhang Liyuan , Yu Yingbo , Yu Runzhong 
Published: October 2020

AbstractMetabolites of the Jinyu 88, Huanong 18, and Demeiya 9 maize varieties from the same origin were isolated and identified by GC–MS, and the specific metabolites and metabolic mechanisms of these three varieties of maize were preliminarily analysed and discussed. The metabolites were extracted with 80% methanol and derived with N,O-bis(trimethylsilyl)trifluoroacetamide. A total of 59 metabolites were identified. The specific metabolites of these three varieties of maize were identified. Four possible unknown-structure metabolites were hypothesized. The results showed that the specific metabolites of JY88 were only involved in fatty acid metabolism. The specific metabolites of HN18 were determined to be involved in fatty acid metabolism, glucose metabolism, and phytosterol metabolism. The specific metabolites of DM9 were observed to participate in glucose metabolism and fatty acid metabolism. The disease resistance of HN18 was higher than that of DM9, and its grain bulk density was higher than that of DM9. JY88 was determined to be significantly different from the other two varieties, and its appearance and disease resistance were worse than those of the other two varieties. The variety with the highest nutritional value was determined to be HN18, and the variety with the lowest nutritional value was JY88. This finding indicated that different maize varieties from the same origin had different metabolites and different metabolic mechanisms, which caused the three maize varieties to exhibit different characteristics and qualities.
High-throughput continuous-flow microfluidic electroporation of mRNA into primary human T cells for applications in cellular therapy manufacturing
Authors: Lissandrello Charles A. , Santos Jose A. , Hsi Peter , Welch Michaela , Mott Vienna L. , Kim Ernest S. , Chesin Jordan , Haroutunian Nerses J. , Stoddard Aaron G. , Czarnecki Andrew , Coppeta Jonathan R. , Freeman Daniel K. , Flusberg Deborah A. , Balestrini Jenna L. , Tandon Vishal 
Published: October 2020

AbstractImplementation of gene editing technologies such as CRISPR/Cas9 in the manufacture of novel cell-based therapeutics has the potential to enable highly-targeted, stable, and persistent genome modifications without the use of viral vectors. Electroporation has emerged as a preferred method for delivering gene-editing machinery to target cells, but a major challenge remaining is that most commercial electroporation machines are built for research and process development rather than for large-scale, automated cellular therapy manufacturing. Here we present a microfluidic continuous-flow electrotransfection device designed for precise, consistent, and high-throughput genetic modification of target cells in cellular therapy manufacturing applications. We optimized our device for delivery of mRNA into primary human T cells and demonstrated up to 95% transfection efficiency with minimum impact on cell viability and expansion potential. We additionally demonstrated processing of samples comprising up to 500 million T cells at a rate of 20 million cells/min. We anticipate that our device will help to streamline the production of autologous therapies requiring on the order of 10$$^8$$

8

–10$$^9$$

9

cells, and that it is well-suited to scale for production of trillions of cells to support emerging allogeneic therapies.
Early adolescent adversity alters periaqueductal gray/dorsal raphe threat responding in adult female rats
Authors: Moaddab Mahsa , Wright Kristina M. , McDannald Michael A. 
Published: October 2020

AbstractEarly adolescent adversity increases adult risk for anxiety disorders. The ventrolateral periaqueductal gray (vlPAG) and neighboring dorsal raphe (DR) are integral to threat prediction, and are responsive to acute stressors. Here, we tested the hypothesis that early adolescent adversity reshapes vlPAG/DR threat-related cue activity and threat probability signaling. Female, Long Evans rats experienced a battery of adverse adolescent experiences (n = 12), while controls did not (n = 8). Single-unit activity was recorded 50 + days following the final adverse experience, when the adult rats received fear discrimination consisting of danger, uncertainty and safety cues. Despite achieving fear discrimination that was equivalent to controls, vlPAG/DR threat responding was altered in adverse-experienced rats. Early adolescent adversity resulted in a greater proportion of cue-responsive neurons. Cue-excited neurons showed greater increases in firing and cue-inhibited neurons showed greater decreases. Even more, early adversity reduced flexible, threat probability signaling by cue-excited neurons and promoted more rigid, fear output signaling by cue-inhibited neurons. The results reveal long-lasting changes in vlPAG/DR threat responding resulting from early adolescent adversity.
Impact of hall and ion slip in a thermally stratified nanofluid flow comprising Cu and Al2O3 nanoparticles with nonuniform source/sink
Authors: Gul Nosheen , Ramzan Muhammad , Chung Jae Dong , Kadry Seifedine , Chu Yu-Ming 
Published: October 2020

AbstractNanofluids play a pivotal role in the heat transport phenomenon and are essential in the cooling process of small gadgets like computer microchips and other related applications in microfluidics. Having such amazing applications of nanofluids, we intend to present a theoretical analysis of the thermally stratified 3D flow of nanofluid containing nano solid particles (Cu and Al2O3) over a nonlinear stretchable sheet with Ion and Hall slip effects. Moreover, the features of buoyance effect and non-uniform heat source/skin are also analyzed. For the study of numerically better results, Tawari and Das model is adopted here. For the conversion of the system of partial differential equations into ordinary differential equations, apposite transformations are engaged and are tackled by utilizing the bvp4c scheme of MATLAB software. The effects of dimensionless parameters on velocity and temperature profiles are depicted with the help of graphs. Additionally, the Skin friction coefficient and Nusselt number for the practical applications are examined in the tabular form. Verification of the current study by comparing it with an already published work in a special case is also a part of this study. Results show that the thermal performance of copper nanoparticles is more than alumina nanoparticles. An upsurge in the temperature of nanofluid is observed when the strength of the magnetic field is enhanced. However, the temperature of partially ionized nanofluid is significantly lowered because of the collisions of electrons and ions.
Characterizing microfluidic approaches for a fast and efficient reagent exchange in single-molecule studies
Authors: Madariaga-Marcos Julene , Corti Roberta , Hormeño Silvia , Moreno-Herrero Fernando 
Published: October 2020

AbstractSingle-molecule experiments usually take place in flow cells. This experimental approach is essential for experiments requiring a liquid environment, but is also useful to allow the exchange of reagents before or during measurements. This is crucial in experiments that need to be triggered by ligands or require a sequential addition of proteins. Home-fabricated flow cells using two glass coverslips and a gasket made of paraffin wax are a widespread approach. The volume of the flow cell can be controlled by modifying the dimensions of the channel while the reagents are introduced using a syringe pump. In this system, high flow rates disturb the biological system, whereas lower flow rates lead to the generation of a reagent gradient in the flow cell. For very precise measurements it is thus desirable to have a very fast exchange of reagents with minimal diffusion. We propose the implementation of multistream laminar microfluidic cells with two inlets and one outlet, which achieve a minimum fluid switching time of 0.25 s. We additionally define a phenomenological expression to predict the boundary switching time for a particular flow cell cross section. Finally, we study the potential applicability of the platform to study kinetics at the single molecule level.
The fingerprints of climate warming on cereal crops phenology and adaptation options
Authors: Fatima Zartash , Ahmed Mukhtar , Hussain Mubshar , Abbas Ghulam , Ul-Allah Sami , Ahmad Shakeel , Ahmed Niaz , Ali Muhammad Arif , Sarwar Ghulam , Haque Ehsan ul , Iqbal Pakeeza , Hussain Sajjad 
Published: October 2020

AbstractGrowth and development of cereal crops are linked to weather, day length and growing degree-days (GDDs) which make them responsive to the specific environments in specific seasons. Global temperature is rising due to human activities such as burning of fossil fuels and clearance of woodlands for building construction. The rise in temperature disrupts crop growth and development. Disturbance mainly causes a shift in phenological development of crops and affects their economic yield. Scientists and farmers adapt to these phenological shifts, in part, by changing sowing time and cultivar shifts which may increase or decrease crop growth duration. Nonetheless, climate warming is a global phenomenon and cannot be avoided. In this scenario, food security can be ensured by improving cereal production through agronomic management, breeding of climate-adapted genotypes and increasing genetic biodiversity. In this review, climate warming, its impact and consequences are discussed with reference to their influences on phenological shifts. Furthermore, how different cereal crops adapt to climate warming by regulating their phenological development is elaborated. Based on the above mentioned discussion, different management strategies to cope with climate warming are suggested.