bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity
Authors: Fernández-Tussy Pablo , Rodríguez-Agudo Rubén , Fernández-Ramos David , Barbier-Torres Lucía , Zubiete-Franco Imanol , Davalillo Sergio López de , Herraez Elisa , Goikoetxea-Usandizaga Naroa , Lachiondo-Ortega Sofia , Simón Jorge , Lopitz-Otsoa Fernando , Juan Virginia Gutiérrez-de , McCain Misti V. , Perugorria Maria J. , Mabe Jon , Navasa Nicolás , Rodrigues Cecilia M. P. , Fabregat Isabel , Boix Loreto , Sapena Victor , Anguita Juan , Lu Shelly C. , Mato José M. , Banales Jesus M. , Villa Erica , Reeves Helen L. , Bruix Jordi , Reig Maria , Marin Jose J. G. , Delgado Teresa C. , Martínez-Chantar María L. 
Published: May 2021

AbstractDysregulation of miRNAs is a hallmark of cancer, modulating oncogenes, tumor suppressors, and drug responsiveness. The multi-kinase inhibitor sorafenib is one of the first-line drugs for advanced hepatocellular carcinoma (HCC), although the outcome for treated patients is heterogeneous. The identification of predictive biomarkers and targets of sorafenib efficacy are sorely needed. Thus, selected top upregulated miRNAs from the C19MC cluster were analyzed in different hepatoma cell lines compared to immortalized liver human cells, THLE-2 as control. MiR-518d-5p showed the most consistent upregulation among them. Thus, miR-518d-5p was measured in liver tumor/non-tumor samples of two distinct cohorts of HCC patients (n = 16 andn = 20, respectively). Circulating miR-518d-5p was measured in an independent cohort of HCC patients receiving sorafenib treatment (n = 100), where miR-518d-5p was analyzed in relation to treatment duration and patient’s overall survival. In vitro and in vivo studies were performed in human hepatoma BCLC3 and Huh7 cells to analyze the effect of miR-518d-5p inhibition/overexpression during the response to sorafenib. Compared with healthy individuals, miR-518d-5p levels were higher in hepatic and serum samples from HCC patients (n = 16) and in an additional cohort of tumor/non-tumor paired samples (n = 20). MiR-518d-5p, through the inhibition of c-Jun and its mitochondrial target PUMA, desensitized human hepatoma cells and mouse xenograft to sorafenib-induced apoptosis. Finally, serum miR-518d-5p was assessed in 100 patients with HCC of different etiologies and BCLC-stage treated with sorafenib. In BCLC-C patients, higher serum miR-518d-5p at diagnosis was associated with shorter sorafenib treatment duration and survival. Hence, hepatic miR-518d-5p modulates sorafenib resistance in HCC through inhibition of c-Jun/PUMA-induced apoptosis. Circulating miR-518d-5p emerges as a potential lack of response biomarker to sorafenib in BCLC-C HCC patients.
KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway
Authors: Xu Yitong , Wang Chenglong , Jiang Xizi , Zhang Yao , Su Hongbo , Jiang Jun , Ren Hongjiu , Qiu Xueshan 
Published: May 2021

AbstractLung cancer is the leading cause of cancer-related death worldwide. KLHL38 has been reported to be upregulated during diapause but downregulated after androgen treatment during the reversal of androgen-dependent skeletal muscle atrophy. This study aimed to clarify the role of KLHL38 in non-small cell lung cancer (NSCLC). KLHL38 expression was evaluated in tumor and adjacent normal tissues from 241 patients with NSCLC using immunohistochemistry and real-time PCR, and its association with clinicopathological parameters was analyzed. KLHL38 levels positively correlated with tumor size, lymph node metastasis, and pathological tumor-node-metastasis stage (all P < 0.001). In NSCLC cell lines, KLHL38 overexpression promoted PTEN ubiquitination, thereby activating Akt signaling. It also promoted cell proliferation, migration, and invasion by upregulating the expression of genes encoding cyclin D1, cyclin B, c-myc, RhoA, and MMP9, while downregulating the expression of p21 and E-cadherin. In vivo experiments in nude mice further confirmed that KLHL38 promotes NSCLC progression through Akt signaling pathway activation. Together, these results indicate that KLHL38 is a valuable candidate prognostic biomarker and potential therapeutic target for NSCLC.
Neocortex- and hippocampus-specific deletion of Gabrg2 causes temperature-dependent seizures in mice
Authors: Li Xinxiao , Guo Shengnan , Xu Siying , Chen Zhangping , Wang Lei , Ding Jiangwei , Huo Junming , Xiao Lifei , He Zhenquan , Jin Zhe , Wang Feng , Sun Tao 
Published: May 2021

AbstractMutations in the GABRG2 gene encoding the γ-aminobutyric acid (GABA) A receptor gamma 2 subunit are associated with genetic epilepsy with febrile seizures plus, febrile seizures plus, febrile seizures, and other symptoms of epilepsy. However, the mechanisms underlying Gabrg2-mediated febrile seizures are poorly understood. Here, we used the Cre/loxP system to generate conditional knockout (CKO) mice with deficient Gabrg2 in the hippocampus and neocortex. Heterozygous CKO mice (Gabrg2fl/wtCre+) exhibited temperature-dependent myoclonic jerks, generalised tonic-clonic seizures, increased anxiety-like symptoms, and a predisposition to induce seizures. Cortical electroencephalography showed the hyperexcitability in response to temperature elevation in Gabrg2fl/wtCre+ mice, but not in wild-type mice. Gabrg2fl/wtCre+ mice exhibited spontaneous seizures and susceptibility to temperature-induced seizures. Loss of neurons were observed in cortical layers V–VI and hippocampus of Gabrg2fl/wtCre+ mice. Furthermore, the latency of temperature- or pentylenetetrazol-induced seizures were significantly decreased in Gabrg2fl/wtCre+ mice compared with wild-type mice. In summary, Gabrg2fl/wtCre+ mice with Gabrg2 deletion in the neocortex and hippocampus reproduce many features of febrile seizures and therefore provide a novel model to further understand this syndrome at the cellular and molecular level.
Nanonet: Low-temperature-processed tellurium nanowire network for scalable p-type field-effect transistors and a highly sensitive phototransistor array
Authors: Naqi Muhammad , Choi Kyung Hwan , Yoo Hocheon , Chae Sudong , Kim Bum Jun , Oh Seungbae , Jeon Jiho , Wang Cong , Liu Na , Kim Sunkook , Choi Jae-Young 
Published: May 2021

AbstractLow-temperature-processed semiconductors are an emerging need for next-generation scalable electronics, and these semiconductors need to feature large-area fabrication, solution processability, high electrical performance, and wide spectral optical absorption properties. Although various strategies of low-temperature-processed n-type semiconductors have been achieved, the development of high-performance p-type semiconductors at low temperature is still limited. Here, we report a unique low-temperature-processed method to synthesize tellurium nanowire networks (Te-nanonets) over a scalable area for the fabrication of high-performance large-area p-type field-effect transistors (FETs) with uniform and stable electrical and optical properties. Maximum mobility of 4.7 cm2/Vs, an on/off current ratio of 1 × 104, and a maximum transconductance of 2.18 µS are achieved. To further demonstrate the applicability of the proposed semiconductor, the electrical performance of a Te-nanonet-based transistor array of 42 devices is also measured, revealing stable and uniform results. Finally, to broaden the applicability of p-type Te-nanonet-based FETs, optical measurements are demonstrated over a wide spectral range, revealing an exceptionally uniform optical performance.
A sand fly salivary protein acts as a neutrophil chemoattractant
Authors: Guimaraes-Costa Anderson B. , Shannon John P. , Waclawiak Ingrid , Oliveira Jullyanna , Meneses Claudio , de Castro Waldione , Wen Xi , Brzostowski Joseph , Serafim Tiago D. , Andersen John F. , Hickman Heather D. , Kamhawi Shaden , Valenzuela Jesus G. , Oliveira Fabiano 
Published: May 2021

AbstractApart from bacterial formyl peptides or viral chemokine mimicry, a non-vertebrate or insect protein that directly attracts mammalian innate cells such as neutrophils has not been molecularly characterized. Here, we show that members of sand fly yellow salivary proteins induce in vitro chemotaxis of mouse, canine and human neutrophils in transwell migration or EZ-TAXIScan assays. We demonstrate murine neutrophil recruitment in vivo using flow cytometry and two-photon intravital microscopy in Lysozyme-M-eGFP transgenic mice. We establish that the structure of this ~ 45 kDa neutrophil chemotactic protein does not resemble that of known chemokines. This chemoattractant acts through a G-protein-coupled receptor and is dependent on calcium influx. Of significance, this chemoattractant protein enhances lesion pathology (P < 0.0001) and increases parasite burden (P < 0.001) in mice upon co-injection with Leishmania parasites, underlining the impact of the sand fly salivary yellow proteins on disease outcome. These findings show that some arthropod vector-derived factors, such as this chemotactic salivary protein, activate rather than inhibit the host innate immune response, and that pathogens take advantage of these inflammatory responses to establish in the host.
Bell-state tomography in a silicon many-electron artificial molecule
Authors: Leon Ross C. C. , Yang Chih Hwan , Hwang Jason C. C. , Camirand Lemyre Julien , Tanttu Tuomo , Huang Wei , Huang Jonathan Y. , Hudson Fay E. , Itoh Kohei M. , Laucht Arne , Pioro-Ladrière Michel , Saraiva Andre , Dzurak Andrew S. 
Published: May 2021

AbstractAn error-corrected quantum processor will require millions of qubits, accentuating the advantage of nanoscale devices with small footprints, such as silicon quantum dots. However, as for every device with nanoscale dimensions, disorder at the atomic level is detrimental to quantum dot uniformity. Here we investigate two spin qubits confined in a silicon double quantum dot artificial molecule. Each quantum dot has a robust shell structure and, when operated at an occupancy of 5 or 13 electrons, has single spin-$$\frac{1}{2}$$

1

2

valence electron in its p- or d-orbital, respectively. These higher electron occupancies screen static electric fields arising from atomic-level disorder. The larger multielectron wavefunctions also enable significant overlap between neighbouring qubit electrons, while making space for an interstitial exchange-gate electrode. We implement a universal gate set using the magnetic field gradient of a micromagnet for electrically driven single qubit gates, and a gate-voltage-controlled inter-dot barrier to perform two-qubit gates by pulsed exchange coupling. We use this gate set to demonstrate a Bell state preparation between multielectron qubits with fidelity 90.3%, confirmed by two-qubit state tomography using spin parity measurements.
Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden
Authors: Peneder Peter , Stütz Adrian M. , Surdez Didier , Krumbholz Manuela , Semper Sabine , Chicard Mathieu , Sheffield Nathan C. , Pierron Gaelle , Lapouble Eve , Tötzl Marcus , Ergüner Bekir , Barreca Daniele , Rendeiro André F. , Agaimy Abbas , Boztug Heidrun , Engstler Gernot , Dworzak Michael , Bernkopf Marie , Taschner-Mandl Sabine , Ambros Inge M. , Myklebost Ola , Marec-Bérard Perrine , Burchill Susan Ann , Brennan Bernadette , Strauss Sandra J. , Whelan Jeremy , Schleiermacher Gudrun , Schaefer Christiane , Dirksen Uta , Hutter Caroline , Boye Kjetil , Ambros Peter F. , Delattre Olivier , Metzler Markus , Bock Christoph , Tomazou Eleni M. 
Published: May 2021

AbstractSequencing of cell-free DNA in the blood of cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic analysis method and demonstrate its utility on 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. Our method achieves sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. Moreover, we benchmark different metrics for cell-free DNA fragmentation analysis, and we introduce the LIQUORICE algorithm for detecting circulating tumor DNA based on cancer-specific chromatin signatures. Finally, we combine several fragmentation-based metrics into an integrated machine learning classifier for liquid biopsy analysis that exploits widespread epigenetic deregulation and is tailored to cancers with low mutation rates. Clinical associations highlight the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. In summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent genetic aberrations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers.
Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis
Authors: van der Lelie Daniel , Oka Akihiko , Taghavi Safiyh , Umeno Junji , Fan Ting-Jia , Merrell Katherine E. , Watson Sarah D. , Ouellette Lisa , Liu Bo , Awoniyi Muyiwa , Lai Yunjia , Chi Liang , Lu Kun , Henry Christopher S. , Sartor R. Balfour 
Published: May 2021

AbstractEnvironmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.
Robust coherent control of solid-state spin qubits using anti-Stokes excitation
Authors: Wang Jun-Feng , Yan Fei-Fei , Li Qiang , Liu Zheng-Hao , Cui Jin-Ming , Liu Zhao-Di , Gali Adam , Xu Jin-Shi , Li Chuan-Feng , Guo Guang-Can 
Published: May 2021

AbstractOptically addressable solid-state color center spin qubits have become important platforms for quantum information processing, quantum networks and quantum sensing. The readout of color center spin states with optically detected magnetic resonance (ODMR) technology is traditionally based on Stokes excitation, where the energy of the exciting laser is higher than that of the emission photons. Here, we investigate an unconventional approach using anti-Stokes excitation to detect the ODMR signal of silicon vacancy defect spin in silicon carbide, where the exciting laser has lower energy than the emitted photons. Laser power, microwave power and temperature dependence of the anti-Stokes excited ODMR are systematically studied, in which the behavior of ODMR contrast and linewidth is shown to be similar to that of Stokes excitation. However, the ODMR contrast is several times that of the Stokes excitation. Coherent control of silicon vacancy spin under anti-Stokes excitation is then realized at room temperature. The spin coherence properties are the same as those of Stokes excitation, but with a signal contrast that is around three times greater. To illustrate the enhanced spin readout contrast under anti-Stokes excitation, we also provide a theoretical model. The experiments demonstrate that the current anti-Stokes excitation ODMR approach has promising applications in quantum information processing and quantum sensing.
Dynamic methylation of histone H3K18 in differentiating Theileria parasites
Authors: Cheeseman Kevin , Jannot Guillaume , Lourenço Nelly , Villares Marie , Berthelet Jérémy , Calegari-Silva Teresa , Hamroune Juliette , Letourneur Franck , Rodrigues-Lima Fernando , Weitzman Jonathan B. 
Published: May 2021

AbstractLysine methylation on histone tails impacts genome regulation and cell fate determination in many developmental processes. Apicomplexa intracellular parasites cause major diseases and they have developed complex life cycles with fine-tuned differentiation events. Yet, apicomplexa genomes have few transcription factors and little is known about their epigenetic control systems. Tick-borne Theileria apicomplexa species have relatively small, compact genomes and a remarkable ability to transform leucocytes in their bovine hosts. Here we report enriched H3 lysine 18 monomethylation (H3K18me1) on the gene bodies of repressed genes in Theileria macroschizonts. Differentiation to merozoites (merogony) leads to decreased H3K18me1 in parasite nuclei. Pharmacological manipulation of H3K18 acetylation or methylation impacted parasite differentiation and expression of stage-specific genes. Finally, we identify a parasite SET-domain methyltransferase (TaSETup1) that can methylate H3K18 and represses gene expression. Thus, H3K18me1 emerges as an important epigenetic mark which controls gene expression and stage differentiation in Theileria parasites.
Magnetic charge propagation upon a 3D artificial spin-ice
Authors: May A. , Saccone M. , van den Berg A. , Askey J. , Hunt M. , Ladak S. 
Published: May 2021

AbstractMagnetic charge propagation in spin-ice materials has yielded a paradigm-shift in science, allowing the symmetry between electricity and magnetism to be studied. Recent work is now suggesting the spin-ice surface may be important in mediating the ordering and associated phase space in such materials. Here, we detail a 3D artificial spin-ice, which captures the exact geometry of bulk systems, allowing magnetic charge dynamics to be directly visualized upon the surface. Using magnetic force microscopy, we observe vastly different magnetic charge dynamics along two principal directions. For a field applied along the surface termination, local energetics force magnetic charges to nucleate over a larger characteristic distance, reducing their magnetic Coulomb interaction and producing uncorrelated monopoles. In contrast, applying a field transverse to the surface termination yields highly correlated monopole-antimonopole pairs. Detailed simulations suggest it is the difference in effective chemical potential as well as the energy landscape experienced during dynamics that yields the striking differences in monopole transport.
Photon bubble turbulence in cold atom gases
Authors: Giampaoli R. , Rodrigues João D. , Rodrigues José-António , Mendonça J. T. 
Published: May 2021

AbstractTurbulent radiation flow is commonplace in systems with strong, incoherent, light-matter interactions. In astrophysical contexts, photon bubble turbulence is considered a key mechanism behind enhanced radiation transport, and its importance has been widely asserted for a variety of high energy objects such as accretion disks and massive stars. Here, we show that analogous conditions to those of dense astrophysical objects can be obtained in large clouds of cold atoms, prepared in a laser-cooling experiment, driven close to a sharp electronic resonance. By accessing the spatially-resolved atom density, we are able to identify a photon bubble instability and the resulting regime of photon bubble turbulence. We also develop a theoretical model describing the coupled dynamics of both photon and atom gases, which accurately describes the statistical properties of the turbulent regime. This study thus opens the possibility of simulating radiation-dominated astrophysical systems in cold atom experiments.
Structures of the human LONP1 protease reveal regulatory steps involved in protease activation
Authors: Shin Mia , Watson Edmond R. , Song Albert S. , Mindrebo Jeffrey T. , Novick Scott J. , Griffin Patrick R. , Wiseman R. Luke , Lander Gabriel C. 
Published: May 2021

AbstractThe human mitochondrial AAA+ protein LONP1 is a critical quality control protease involved in regulating diverse aspects of mitochondrial biology including proteostasis, electron transport chain activity, and mitochondrial transcription. As such, genetic or aging-associated imbalances in LONP1 activity are implicated in pathologic mitochondrial dysfunction associated with numerous human diseases. Despite this importance, the molecular basis for LONP1-dependent proteolytic activity remains poorly defined. Here, we solved cryo-electron microscopy structures of human LONP1 to reveal the underlying molecular mechanisms governing substrate proteolysis. We show that, like bacterial Lon, human LONP1 adopts both an open and closed spiral staircase orientation dictated by the presence of substrate and nucleotide. Unlike bacterial Lon, human LONP1 contains a second spiral staircase within its ATPase domain that engages substrate as it is translocated toward the proteolytic chamber. Intriguingly, and in contrast to its bacterial ortholog, substrate binding within the central ATPase channel of LONP1 alone is insufficient to induce the activated conformation of the protease domains. To successfully induce the active protease conformation in substrate-bound LONP1, substrate binding within the protease active site is necessary, which we demonstrate by adding bortezomib, a peptidomimetic active site inhibitor of LONP1. These results suggest LONP1 can decouple ATPase and protease activities depending on whether AAA+ or both AAA+ and protease domains bind substrate. Importantly, our structures provide a molecular framework to define the critical importance of LONP1 in regulating mitochondrial proteostasis in health and disease.
Cooperative stator assembly of bacterial flagellar motor mediated by rotation
Authors: Ito Kenta I. , Nakamura Shuichi , Toyabe Shoichi 
Published: May 2021

AbstractCooperativity has a central place in biological regulation, providing robust and highly-sensitive regulation. The bacterial flagellar motor implements autonomous torque regulation based on the stator’s dynamic structure; the stator units bind to and dissociate from the motor dynamically in response to environmental changes. However, the mechanism of this dynamic assembly is not fully understood. Here, we demonstrate the cooperativity in the stator assembly dynamics. The binding is slow at the stalled state, but externally forced rotation as well as driving by motor torque in either direction boosts the stator binding. Hence, once a stator unit binds, it drives the rotor and triggers the avalanche of succeeding bindings. This cooperative mechanism based on nonequilibrium allostery accords with the recently-proposed gear-type coupling between the rotor and stator.