bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a miRNA-controlled dual-sensing system and its application for targeting miR-21 signaling in tumorigenesis
Authors: Seo Yoona , Kim Sung Soo , Kim Namdoo , Cho Sungchan , Park Jong Bae , Kim Jong Heon 
Published: December 2020

AbstractMicroRNAs (miRNAs) are considered to be strong prognostic markers and key therapeutic targets in human diseases, especially cancer. A sensitive monitoring platform for cancer-associated miRNA (oncomiR) action is needed for mechanistic studies, preclinical evaluation, and inhibitor screening. In this study, we developed and systemically applied a sensitive and efficient lentivirus-based system for monitoring oncomiR actions, essentially miR-21. The specificity and sensitivity of “miRDREL” against various oncomiRs were validated by checking for tight correlations between their expression and targeting efficacy. Experiments based on the transfection of synthetic mimics and antagomir-mediated depletion of oncomiRs further confirmed the specificity of the system. Systemic application of miRDRELs to natural oncomiR targets, knockdown of key microprocessors, and physiological triggering of oncomiRs also demonstrated that the system is an effective tool for monitoring cellular oncomiR action. Importantly, molecular modeling-based screening confirmed the action of the miR-21-targeting drug ivermectin and led to the identification of a new effective derivative, GW4064, for inhibiting oncogenic DDX23-miR-21 signaling. Furthermore, proteomic-kinase inhibitor screenings identified a novel oncogenic kinome-DDX23-miR-21 axis and thus expands our understanding of miR-21 targeting therapeutics in tumorigenesis. Taken together, these data indicate that miRDREL and its versatile application have great potential in basic, preclinical studies and drug development pipelines for miRNA-related diseases, especially cancer.
Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients
Authors: Visram Alissa , Al Saleh Abdullah S. , Parmar Harsh , McDonald Jennifer S. , Lieske John C. , Vaxman Iuliana , Muchtar Eli , Hobbs Miriam , Fonder Amie , Hwa Yi L. , Buadi Francis K. , Dingli David , Lacy Martha Q. , Dispenzieri Angela , Kapoor Prashant , Hayman Suzanne R. , Warsame Rahma , Kourelis Taxiarchis V. , Siddiqui Mustaqeem , Gonsalves Wilson I. , Lust John A. , Kyle Robert A. , Vincent Rajkumar S. , Gertz Morie A. , Kumar Shaji K. , Leung Nelson 
Published: December 2020

AbstractA 24-h urine protein collection (24hUP), the gold standard for measuring albuminuria in systemic AL amyloidosis, is cumbersome and inaccurate. We retrospectively reviewed 575 patients with systemic AL amyloidosis to assess the correlation between a urine albumin to creatinine ratio (uACR) and the 24hUP. The uACR correlated strongly with 24hUP at diagnosis (Pearson’s r = 0.87, 95% CI 0.83–0.90) and during the disease course (Pearson’s r = 0.88, 95% CI 0.86–0.90). A uACR ≥300 mg/g estimated a 24hUP ≥ 500 mg with a sensitivity of 92% and specificity of 97% (area under the receiver operating curve = 0.938, 95% CI 0.919–0.957). A uACR cutoff of 3600 mg/g best predicted a 24hUP > 5000 g (sensitivity 93%, specificity 94%), and renal stage at diagnosis was strongly concordant using either 24hUP or uACR as the proteinuria measure (k = 0.823, 95% CI 0.728–0.919). In patients with serial urine collections, a > 30% decrease in uACR predicted a > 30% decrease in 24hUP with a sensitivity of 94%. In conclusion, the uACR is a reliable and convenient method for ruling out proteinuria >500 mg per day, prognosticating renal outcomes, and assessing renal response to therapy. Further studies are needed to validate the uACR cutoffs proposed in this study.
Linc00426 accelerates lung adenocarcinoma progression by regulating miR-455-5p as a molecular sponge
Authors: Li Hongli , Mu Qingjie , Zhang Guoxin , Shen Zhixin , Zhang Yuanyuan , Bai Jun , Zhang Liping , Zhou Dandan , Zheng Quan , Shi Lihong , Su Wenxia , Yin Chonggao , Zhang Baogang 
Published: December 2020

AbstractIncreasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.
A tactile sensor system with sensory neurons and a perceptual synaptic network based on semivolatile carbon nanotube transistors
Authors: Kim Sungho , Lee Yongwoo , Kim Hee-Dong , Choi Sung-Jin 
Published: December 2020

AbstractThe human sensory system has a fascinating stimulus-detection capability attributed to the fact that the feature (pattern) of an input stimulus can be extracted through perceptual learning. Therefore, sensory information can be organized and identified efficiently based on iterative experiences, whereby the sensing ability is improved. Specifically, the distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. Herein, we demonstrate an artificial tactile sensor system with a sensory neuron and a perceptual synaptic network composed of a single device: a semivolatile carbon nanotube transistor. The system can differentiate the temporal features of tactile patterns, and its recognition accuracy can be improved by an iterative learning process. Furthermore, the developed circuit model of the system provides quantitative analytical and product-level feasibility. This work is a step toward the design and use of a neuromorphic sensory system with a learning capability for potential applications in robotics and prosthetics.
Enhanced analog synaptic behavior of SiNx/a-Si bilayer memristors through Ge implantation
Authors: Kim Keonhee , Park Soojin , Hu Su Man , Song Jonghan , Lim Weoncheol , Jeong Yeonjoo , Kim Jaewook , Lee Suyoun , Kwak Joon Young , Park Jongkil , Park Jong Keuk , Ju Byeong-Kwon , Jeong Doo Seok , Kim Inho 
Published: December 2020

AbstractConductive bridging random access memory (CBRAM) has been considered to be a promising emerging device for artificial synapses in neuromorphic computing systems. Good analog synaptic behaviors, such as linear and symmetric synapse updates, are desirable to provide high learning accuracy. Although numerous efforts have been made to develop analog CBRAM for years, the stochastic and abrupt formation of conductive filaments hinders its adoption. In this study, we propose a novel approach to enhance the synaptic behavior of a SiNx/a-Si bilayer memristor through Ge implantation. The SiNx and a-Si layers serve as switching and internal current limiting layers, respectively. Ge implantation induces structural defects in the bulk and surface regions of the a-Si layer, enabling spatially uniform Ag migration and nanocluster formation in the upper SiNx layer and increasing the conductance of the a-Si layer. As a result, the analog synaptic behavior of the SiNx/a-Si bilayer memristor, such as the nonlinearity, on/off ratio, and retention time, is remarkably improved. An artificial neural network simulation shows that the neuromorphic system with the implanted SiNx/a-Si memristor provides a 91.3% learning accuracy mainly due to the improved linearity.
Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system
Authors: Chevalier Grégoire , Siopi Eleni , Guenin-Macé Laure , Pascal Maud , Laval Thomas , Rifflet Aline , Boneca Ivo Gomperts , Demangel Caroline , Colsch Benoit , Pruvost Alain , Chu-Van Emeline , Messager Aurélie , Leulier François , Lepousez Gabriel , Eberl Gérard , Lledo Pierre-Marie 
Published: December 2020

AbstractDepression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.
Using metacommunity ecology to understand environmental metabolomes
Authors: Danczak Robert E. , Chu Rosalie K. , Fansler Sarah J. , Goldman Amy E. , Graham Emily B. , Tfaily Malak M. , Toyoda Jason , Stegen James C. 
Published: December 2020

AbstractEnvironmental metabolomes are fundamentally coupled to microbially-linked biogeochemical processes within ecosystems. However, significant gaps exist in our understanding of their spatiotemporal organization, limiting our ability to uncover transferrable principles and predict ecosystem function. We propose that a theoretical paradigm, which integrates concepts from metacommunity ecology, is necessary to reveal underlying mechanisms governing metabolomes. We call this synthesis between ecology and metabolomics ‘meta-metabolome ecology’ and demonstrate its utility using a mass spectrometry dataset. We developed three relational metabolite dendrograms using molecular properties and putative biochemical transformations and performed ecological null modeling. Based upon null modeling results, we show that stochastic processes drove molecular properties while biochemical transformations were structured deterministically. We further suggest that potentially biochemically active metabolites were more deterministically assembled than less active metabolites. Understanding variation in the influences of stochasticity and determinism provides a way to focus attention on which meta-metabolomes and which parts of meta-metabolomes are most likely to be important to consider in mechanistic models. We propose that this paradigm will allow researchers to study the connections between ecological systems and their molecular processes in previously inaccessible detail.
Coexistence of distinct skyrmion phases observed in hybrid ferromagnetic/ferrimagnetic multilayers
Authors: Mandru Andrada-Oana , Yıldırım Oğuz , Tomasello Riccardo , Heistracher Paul , Penedo Marcos , Giordano Anna , Suess Dieter , Finocchio Giovanni , Hug Hans Josef 
Published: December 2020

AbstractMaterials hosting magnetic skyrmions at room temperature could enable compact and energetically-efficient storage such as racetrack memories, where information is coded by the presence/absence of skyrmions forming a moving chain through the device. The skyrmion Hall effect leading to their annihilation at the racetrack edges can be suppressed, for example, by antiferromagnetically-coupled skyrmions. However, avoiding modifications of the inter-skyrmion distances remains challenging. As a solution, a chain of bits could also be encoded by two different solitons, such as a skyrmion and a chiral bobber, with the limitation that it has solely been realized in B20-type materials at low temperatures. Here, we demonstrate that a hybrid ferro/ferri/ferromagnetic multilayer system can host two distinct skyrmion phases at room temperature, namely tubular and partial skyrmions. Furthermore, the tubular skyrmion can be converted into a partial skyrmion. Such systems may serve as a platform for designing memory applications using distinct skyrmion types.
AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion
Authors: Schuster Anne , Klein Eliane , Neirinckx Virginie , Knudsen Arnon Møldrup , Fabian Carina , Hau Ann-Christin , Dieterle Monika , Oudin Anais , Nazarov Petr V. , Golebiewska Anna , Muller Arnaud , Perez-Hernandez Daniel , Rodius Sophie , Dittmar Gunnar , Bjerkvig Rolf , Herold-Mende Christel , Klink Barbara , Kristensen Bjarne Winther , Niclou Simone P. 
Published: December 2020

AbstractThe infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted.
Ru(II)Porphyrinate-based molecular nanoreactor for carbene insertion reactions and quantitative formation of rotaxanes by active-metal-template syntheses
Authors: Fontana Liniquer A. , Almeida Marlon P. , Alcântara Arthur F. P. , Rigolin Vitor H. , Ribeiro Marcos A. , Barros Wdeson P. , Megiatto Jackson D. 
Published: December 2020

AbstractSelectivity in N–H and S–H carbene insertion reactions promoted by Ru(II)porphyrinates currently requires slow addition of the diazo precursor and large excess of the primary amine and thiol substrates in the reaction medium. Such conditions are necessary to avoid the undesirable carbene coupling and/or multiple carbene insertions. Here, the authors demonstrate that the synergy between the steric shielding provided by a Ru(II)porphyrinate-based macrocycle with a relatively small central cavity and the kinetic stabilization of otherwise labile coordinative bonds, warranted by formation of the mechanical bond, enables single carbene insertions to occur with quantitative efficiency and perfect selectivity even in the presence of a large excess of the diazo precursor and stoichiometric amounts of the primary amine and thiol substrates. As the Ru(II)porphyrinate-based macrocycle bears a confining nanospace and alters the product distribution of the carbene insertion reactions when compared to that of its acyclic version, the former therefore functions as a nanoreactor.
Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice
Authors: Zhang Zhi , Reis Fernando M. C. V. , He Yanlin , Park Jae W. , DiVittorio Johnathon R. , Sivakumar Nilla , van Veen J. Edward , Maesta-Pereira Sandra , Shum Michael , Nichols India , Massa Megan G. , Anderson Shawn , Paul Ketema , Liesa Marc , Ajijola Olujimi A. , Xu Yong , Adhikari Avishek , Correa Stephanie M. 
Published: December 2020

AbstractHomeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Recent advances have revealed the medial preoptic area (MPA) as a key site for the regulation of torpor in mice. The MPA is estrogen-sensitive and estrogens also have potent effects on both temperature and metabolism. Here, we demonstrate that estrogen-sensitive neurons in the MPA can coordinate hypothermia and hypometabolism in mice. Selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, whereas selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor in both female and male mice, their effects on thermoregulation and torpor bout initiation exhibit differences across sex. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.
Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers
Authors: Petrany Michael J. , Swoboda Casey O. , Sun Chengyi , Chetal Kashish , Chen Xiaoting , Weirauch Matthew T. , Salomonis Nathan , Millay Douglas P. 
Published: December 2020

AbstractWhile the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the presence of distinct myonuclear populations emerging in postnatal development as well as aging muscle. Our datasets also provided a platform for discovery of genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.
Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
Authors: Kim Minchul , Franke Vedran , Brandt Bettina , Lowenstein Elijah D. , Schöwel Verena , Spuler Simone , Akalin Altuna , Birchmeier Carmen 
Published: December 2020

AbstractSyncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/).
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds
Authors: Campinoti Sara , Gjinovci Asllan , Ragazzini Roberta , Zanieri Luca , Ariza-McNaughton Linda , Catucci Marco , Boeing Stefan , Park Jong-Eun , Hutchinson John C. , Muñoz-Ruiz Miguel , Manti Pierluigi G. , Vozza Gianluca , Villa Carlo E. , Phylactopoulos Demetra-Ellie , Maurer Constance , Testa Giuseppe , Stauss Hans J. , Teichmann Sarah A. , Sebire Neil J. , Hayday Adrian C. , Bonnet Dominique , Bonfanti Paola 
Published: December 2020

AbstractThe thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.
Quantifying and addressing the prevalence and bias of study designs in the environmental and social sciences
Authors: Christie Alec P. , Abecasis David , Adjeroud Mehdi , Alonso Juan C. , Amano Tatsuya , Anton Alvaro , Baldigo Barry P. , Barrientos Rafael , Bicknell Jake E. , Buhl Deborah A. , Cebrian Just , Ceia Ricardo S. , Cibils-Martina Luciana , Clarke Sarah , Claudet Joachim , Craig Michael D. , Davoult Dominique , De Backer Annelies , Donovan Mary K. , Eddy Tyler D. , França Filipe M. , Gardner Jonathan P. A. , Harris Bradley P. , Huusko Ari , Jones Ian L. , Kelaher Brendan P. , Kotiaho Janne S. , López-Baucells Adrià , Major Heather L. , Mäki-Petäys Aki , Martín Beatriz , Martín Carlos A. , Martin Philip A. , Mateos-Molina Daniel , McConnaughey Robert A. , Meroni Michele , Meyer Christoph F. J. , Mills Kade , Montefalcone Monica , Noreika Norbertas , Palacín Carlos , Pande Anjali , Pitcher C. Roland , Ponce Carlos , Rinella Matt , Rocha Ricardo , Ruiz-Delgado María C. , Schmitter-Soto Juan J. , Shaffer Jill A. , Sharma Shailesh , Sher Anna A. , Stagnol Doriane , Stanley Thomas R. , Stokesbury Kevin D. E. , Torres Aurora , Tully Oliver , Vehanen Teppo , Watts Corinne , Zhao Qingyuan , Sutherland William J. 
Published: December 2020

AbstractBuilding trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.