bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia
Authors: Zhou Cheng , Du Juan , Zhao Liang , Liu Wei , Zhao Tianming , Liang Hui , Fang Peng , Zhang Kaixuan , Zeng Hui 
Published: March 2021

AbstractAcute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma‐associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.
Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells
Authors: Liu Binghua , Wang Weiyan , Shah Arman , Yu Meng , Liu Yang , He Libo , Dang Jinye , Yang Li , Yan Mengli , Ying Yuling , Tang Zihuai , Liu Ke 
Published: March 2021

AbstractSodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.
Evolution of combinatorial diversity in trans-acyltransferase polyketide synthase assembly lines across bacteria
Authors: Helfrich Eric J. N. , Ueoka Reiko , Chevrette Marc G. , Hemmerling Franziska , Lu Xiaowen , Leopold-Messer Stefan , Minas Hannah A. , Burch Adrien Y. , Lindow Steven E. , Piel Jörn , Medema Marnix H. 
Published: March 2021

AbstractTrans-acyltransferase polyketide synthases (trans-AT PKSs) are bacterial multimodular enzymes that biosynthesize diverse pharmaceutically and ecologically important polyketides. A notable feature of this natural product class is the existence of chemical hybrids that combine core moieties from different polyketide structures. To understand the prevalence, biosynthetic basis, and evolutionary patterns of this phenomenon, we developed transPACT, a phylogenomic algorithm to automate global classification of trans-AT PKS modules across bacteria and applied it to 1782 trans-AT PKS gene clusters. These analyses reveal widespread exchange patterns suggesting recombination of extended PKS module series as an important mechanism for metabolic diversification in this natural product class. For three plant-associated bacteria, i.e., the root colonizer Gynuella sunshinyii and the pathogens Xanthomonas cannabis and Pseudomonas syringae, we demonstrate the utility of this computational approach for uncovering cryptic relationships between polyketides, accelerating polyketide mining from fragmented genome sequences, and discovering polyketide variants with conserved moieties of interest. As natural combinatorial hybrids are rare among the more commonly studied cis-AT PKSs, this study paves the way towards evolutionarily informed, rational PKS engineering to produce chimeric trans-AT PKS-derived polyketides.
In situ identification of the metallic state of Ag nanoclusters in oxidative dispersion
Authors: Li Rongtan , Xu Xiaoyan , Zhu Beien , Li Xiao-Yan , Ning Yanxiao , Mu Rentao , Du Pengfei , Li Mengwei , Wang Huike , Liang Jiajie , Chen Yongsheng , Gao Yi , Yang Bing , Fu Qiang , Bao Xinhe 
Published: March 2021

AbstractOxidative dispersion has been widely used in regeneration of sintered metal catalysts and fabrication of single atom catalysts, which is attributed to an oxidation-induced dispersion mechanism. However, the interplay of gas-metal-support interaction in the dispersion processes, especially the gas-metal interaction has not been well illustrated. Here, we show dynamic dispersion of silver nanostructures on silicon nitride surface under reducing/oxidizing conditions and during carbon monoxide oxidation reaction. Utilizing environmental scanning (transmission) electron microscopy and near-ambient pressure photoelectron spectroscopy/photoemission electron microscopy, we unravel a new adsorption-induced dispersion mechanism in such a typical oxidative dispersion process. The strong gas-metal interaction achieved by chemisorption of oxygen on nearly-metallic silver nanoclusters is the internal driving force for dispersion. In situ observations show that the dispersed nearly-metallic silver nanoclusters are oxidized upon cooling in oxygen atmosphere, which could mislead to the understanding of oxidation-induced dispersion. We further understand the oxidative dispersion mechanism from the view of dynamic equilibrium taking temperature and gas pressure into account, which should be applied to many other metals such as gold, copper, palladium, etc. and other reaction conditions.
Gain-switched semiconductor laser driven soliton microcombs
Authors: Weng Wenle , Kaszubowska-Anandarajah Aleksandra , He Jijun , Lakshmijayasimha Prajwal D. , Lucas Erwan , Liu Junqiu , Anandarajah Prince M. , Kippenberg Tobias J. 
Published: March 2021

AbstractDissipative Kerr soliton generation using self-injection-locked III-V lasers has enabled fully integrated hybrid microcombs that operate in turnkey mode and can access microwave repetition rates. Yet, continuous-wave-driven soliton microcombs exhibit low energy conversion efficiency and high optical power threshold, especially when the repetition frequencies are within the microwave range that is convenient for direct detection with off-the-shelf electronics. Here, by actively switching the bias current of injection-locked III-V semiconductor lasers with switching frequencies in the X-band and K-band microwave ranges, we pulse-pump both crystalline and integrated microresonators with picosecond laser pulses, generating soliton microcombs with stable repetition rates and lowering the required average pumping power by one order of magnitude to a record-setting level of a few milliwatts. In addition, we unveil the critical role of the phase profile of the pumping pulses, and implement phase engineering on the pulsed pumping scheme, which allows for the robust generation and the stable trapping of solitons on intracavity pulse pedestals. Our work leverages the advantages of the gain switching and the pulse pumping techniques, and establishes the merits of combining distinct compact comb platforms that enhance the potential of energy-efficient chipscale microcombs.
A scalable unified framework of total and allele-specific counts for cis-QTL, fine-mapping, and prediction
Authors: Liang Yanyu , Aguet François , Barbeira Alvaro N. , Ardlie Kristin , Im Hae Kyung 
Published: March 2021

AbstractGenetic studies of the transcriptome help bridge the gap between genetic variation and phenotypes. To maximize the potential of such studies, efficient methods to identify expression quantitative trait loci (eQTLs) and perform fine-mapping and genetic prediction of gene expression traits are needed. Current methods that leverage both total read counts and allele-specific expression to identify eQTLs are generally computationally intractable for large transcriptomic studies. Here, we describe a unified framework that addresses these needs and is scalable to thousands of samples. Using simulations and data from GTEx, we demonstrate its calibration and performance. For example, mixQTL shows a power gain equivalent to a 29% increase in sample size for genes with sufficient allele-specific read coverage. To showcase the potential of mixQTL, we apply it to 49 GTEx tissues and find 20% additional eQTLs (FDR < 0.05, per tissue) that are significantly more enriched among trait associated variants and candidate cis-regulatory elements comparing to the standard approach.
Monitoring metallic sub-micrometric lithium structures in Li-ion batteries by in situ electron paramagnetic resonance correlated spectroscopy and imaging
Authors: Dutoit Charles-Emmanuel , Tang Mingxue , Gourier Didier , Tarascon Jean-Marie , Vezin Hervé , Salager Elodie 
Published: March 2021

AbstractMonitoring the formation of dendrites or filaments of lithium is of paramount importance for Li-based battery technologies, hence the intense activities in designing in situ techniques to visualize their growth. Herein we report the benefit of correlating in situ electron paramagnetic resonance (EPR) spectroscopy and EPR imaging to analyze the morphology and location of metallic lithium in a symmetric Li/LiPF6/Li electrochemical cell during polarization. We exploit the variations in shape, resonance field and amplitude of the EPR spectra to follow, operando, the nucleation of sub-micrometric Li particles (narrow and symmetrical signal) that conjointly occurs with the fragmentation of bulk Li on the opposite electrode (asymmetrical signal). Moreover, in situ EPR correlated spectroscopy and imaging (spectral-spatial EPR imaging) allows the identification (spectral) and localization (spatial) of the sub-micrometric Li particles created by plating (deposition) or stripping (altered bulk Li surface). We finally demonstrate the possibility to visualize, via in situ EPR imaging, dendrites formed through the separator in the whole cell. Such a technique could be of great help in mastering the Li-electrolyte interface issues that plague the development of solid-state batteries.
Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling
Authors: Brady Lauren , Kriner Michelle , Coleman Ilsa , Morrissey Colm , Roudier Martine , True Lawrence D. , Gulati Roman , Plymate Stephen R. , Zhou Zoey , Birditt Brian , Meredith Rhonda , Geiss Gary , Hoang Margaret , Beechem Joseph , Nelson Peter S. 
Published: March 2021

AbstractMetastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However, there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4, the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases.
Reconfigurable photonics with on-chip single-photon detectors
Authors: Gyger Samuel , Zichi Julien , Schweickert Lucas , Elshaari Ali W. , Steinhauer Stephan , Covre da Silva Saimon F. , Rastelli Armando , Zwiller Val , Jöns Klaus D. , Errando-Herranz Carlos 
Published: March 2021

AbstractIntegrated quantum photonics offers a promising path to scale up quantum optics experiments by miniaturizing and stabilizing complex laboratory setups. Central elements of quantum integrated photonics are quantum emitters, memories, detectors, and reconfigurable photonic circuits. In particular, integrated detectors not only offer optical readout but, when interfaced with reconfigurable circuits, allow feedback and adaptive control, crucial for deterministic quantum teleportation, training of neural networks, and stabilization of complex circuits. However, the heat generated by thermally reconfigurable photonics is incompatible with heat-sensitive superconducting single-photon detectors, and thus their on-chip co-integration remains elusive. Here we show low-power microelectromechanical reconfiguration of integrated photonic circuits interfaced with superconducting single-photon detectors on the same chip. We demonstrate three key functionalities for photonic quantum technologies: 28 dB high-extinction routing of classical and quantum light, 90 dB high-dynamic range single-photon detection, and stabilization of optical excitation over 12 dB power variation. Our platform enables heat-load free reconfigurable linear optics and adaptive control, critical for quantum state preparation and quantum logic in large-scale quantum photonics applications.
Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility
Authors: Spichal Maya , Heestand Bree , Billmyre Katherine Kretovich , Frenk Stephen , Mello Craig C. , Ahmed Shawn 
Published: March 2021

AbstractIn several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.
A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy
Authors: Lybrand Zane R. , Goswami Sonal , Zhu Jingfei , Jarzabek Veronica , Merlock Nikolas , Aktar Mahafuza , Smith Courtney , Zhang Ling , Varma Parul , Cho Kyung-Ok , Ge Shaoyu , Hsieh Jenny 
Published: March 2021

AbstractIn the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.
A multiplexed, next generation sequencing platform for high-throughput detection of SARS-CoV-2
Authors: Aynaud Marie-Ming , Hernandez J. Javier , Barutcu Seda , Braunschweig Ulrich , Chan Kin , Pearson Joel D. , Trcka Daniel , Prosser Suzanna L. , Kim Jaeyoun , Barrios-Rodiles Miriam , Jen Mark , Song Siyuan , Shen Jess , Bruce Christine , Hazlett Bryn , Poutanen Susan , Attisano Liliana , Bremner Rod , Blencowe Benjamin J. , Mazzulli Tony , Han Hong , Pelletier Laurence , Wrana Jeffrey L. 
Published: March 2021

AbstractPopulation scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. Here, we describe “Systematic Parallel Analysis of RNA coupled to Sequencing for Covid-19 screening” (C19-SPAR-Seq), a multiplexed, scalable, readily automated platform for SARS-CoV-2 detection that is capable of analyzing tens of thousands of patient samples in a single run. To address strict requirements for control of assay parameters and output demanded by clinical diagnostics, we employ a control-based Precision-Recall and Receiver Operator Characteristics (coPR) analysis to assign run-specific quality control metrics. C19-SPAR-Seq coupled to coPR on a trial cohort of several hundred patients performs with a specificity of 100% and sensitivity of 91% on samples with low viral loads, and a sensitivity of >95% on high viral loads associated with disease onset and peak transmissibility. This study establishes the feasibility of employing C19-SPAR-Seq for the large-scale monitoring of SARS-CoV-2 and other pathogens.
Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli
Authors: Wang Xuan , Han Jia-Ning , Zhang Xu , Ma Yue-Yuan , Lin Yina , Wang Huan , Li Dian-Jie , Zheng Tao-Ran , Wu Fu-Qing , Ye Jian-Wen , Chen Guo-Qiang 
Published: March 2021

AbstractGenetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bioprocesses is still a challenge in metabolic engineering due to the lack of robustness. Here, we report a robust thermosensitive bio-switch that enables stringent bidirectional control of gene expression over time and levels in living cells. Based on the bio-switch, we obtain tree ring-like colonies with spatially distributed patterns and transformer cells shifting among spherical-, rod- and fiber-shapes of the engineered Escherichia coli. Moreover, fed-batch fermentations of recombinant E. coli are conducted to obtain ordered assembly of tailor-made biopolymers polyhydroxyalkanoates including diblock- and random-copolymer, composed of 3-hydroxybutyrate and 4-hydroxybutyrate with controllable monomer molar fraction. This study demonstrates the possibility of well-organized, chemosynthesis-like block polymerization on a molecular scale by reprogrammed microbes, exemplifying the versatility of thermo-response control for various practical uses.
Millimeter wave photonics with terahertz semiconductor lasers
Authors: Pistore Valentino , Nong Hanond , Vigneron Pierre-Baptiste , Garrasi Katia , Houver Sarah , Li Lianhe , Giles Davies A. , Linfield Edmund H. , Tignon Jerome , Mangeney Juliette , Colombelli Raffaele , Vitiello Miriam S. , Dhillon Sukhdeep S. 
Published: March 2021

AbstractMillimeter wave (mmWave) generation using photonic techniques has so far been limited to the use of near-infrared lasers that are down-converted to the mmWave region. However, such methodologies do not currently benefit from a monolithic architecture and suffer from the quantum defect i.e. the difference in photon energies between the near-infrared and mmWave region, which can ultimately limit the conversion efficiency. Miniaturized terahertz (THz) quantum cascade lasers (QCLs) have inherent advantages in this respect: their low energy photons, ultrafast gain relaxation and high nonlinearities open up the possibility of innovatively integrating both laser action and mmWave generation in a single device. Here, we demonstrate intracavity mmWave generation within THz QCLs over the unprecedented range of 25 GHz to 500 GHz. Through ultrafast time resolved techniques, we highlight the importance of modal phases and that the process is a result of a giant second-order nonlinearity combined with a phase matched process between the THz and mmWave emission. Importantly, this work opens up the possibility of compact, low noise mmWave generation using modelocked THz frequency combs.
Current-induced switching of proximity-induced ferromagnetic surface states in a topological insulator
Authors: Mogi Masataka , Yasuda Kenji , Fujimura Reika , Yoshimi Ryutaro , Ogawa Naoki , Tsukazaki Atsushi , Kawamura Minoru , Takahashi Kei S. , Kawasaki Masashi , Tokura Yoshinori 
Published: March 2021

AbstractElectrical manipulation of magnetization could be an essential function for energy-efficient spintronics technology. A magnetic topological insulator, possessing a magnetically gapped surface state with spin-polarized electrons, not only exhibits exotic topological phases relevant to the quantum anomalous Hall state but also enables the electrical control of its magnetic state at the surface. Here, we demonstrate efficient current-induced switching of the surface ferromagnetism in hetero-bilayers consisting of the topological insulator (Bi1-xSbx)2Te3 and the ferromagnetic insulator Cr2Ge2Te6, where the proximity-induced ferromagnetic surface states play two roles: efficient charge-to-spin current conversion and emergence of large anomalous Hall effect. The sign reversal of the surface ferromagnetic states with current injection is clearly observed, accompanying the nearly full magnetization reversal in the adjacent insulating Cr2Ge2Te6 layer of an optimal thickness range. The present results may facilitate an electrical control of dissipationless topological-current circuits.