bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen receptor-α regulation of microRNA-590 targets FAM171A1—a modifier of breast cancer invasiveness
Authors: Sanawar Rahul , Mohan Dan Vipin , Santhoshkumar Thankayyan R. , Kumar Rakesh , Pillai M. Radhakrishna 
Published: January 2019

AbstractThe pathobiology and aggressiveness of the triple negative breast cancer (TNBC) are influenced by genes that are preferentially expressed in TNBC cells. However, the nature of such genes with the role in invasiveness of TNBC cells is not fully understood. Here, we identified FAM171A1, member (A1) of the family with sequence similarity 171, as an overexpressed candidate gene in TNBC cells and tumors as compared to estrogen receptor-alpha (ERα) positive breast cancer. We found that the expression of FAM171A1 correlates well with the loss of ERα as well as its newly identified target miR590-5p in TNBC but not in ERα-positive cells. In addition, we report that ERα regulates FAM171A1 expression through a mechanism which involves ERα stimulation of miR590-5p expression via binding to its promoter, and in-turn, miR590-5p suppression of FAM171A1 expression. Further, we found that the levels of FAM171A1 correlate well with cancer cell aggressiveness as depletion or overexpression of FAM171A1 confers reduced or increased ability of TNBC cells to form mammospheres, respectively in accordance with the previous report of increased mammosphere formation potential of metastatic cells. In brief, results presented here have demonstrated that ERα regulation of FAM171A1 expression via miR590-5p explains the molecular basis of the noticed reduced levels of FAM171A1 in ER-positive breast cancer cells and that FAM171A1 is a preferably TNBC- overexpressed gene. Further, the noted loss of ERα–miR590-5p axis may upregulate the expression of FAM171A1 and consequently, resulting aggressiveness of TNBC cells. These findings suggest that FAM171A1 might represent a potentially novel therapeutic target for TNBC tumors.
Blockade of CTLA-4 and Tim-3 pathways induces fetal loss with altered cytokine profiles by decidual CD4+T cells
Authors: Wang Songcun , Chen Chunqin , Li Mengdie , Qian Jinfeng , Sun Fengyun , Li Yunyun , Yu Min , Wang Mingyan , Zang Xingxing , Zhu Rui , Li Dajin , Du Meirong 
Published: January 2019

AbstractThe single and/or combination use of immune checkpoint blockade therapies in human infectious diseases and cancer are rapidly expanding. Despite early efforts, substantial uncertainty remains about the safety and efficacy of immune checkpoint blockade in some populations. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are the major targetable co-inhibitory receptors on T cells. Here we showed that in animal studies, treatment with either CTLA-4- or Tim-3-blocking antibody caused greater susceptibility to fetal loss with altered cytokine profiles by decidual CD4+T (dCD4+T) cells. CTLA-4 and Tim-3 pathways appeared to play key roles in maintaining maternal-fetal tolerance by regulating the function of dCD4+T cells. In addition, the abnormality in number and functionality of dCTLA-4+Tim-3+CD4+T cells was associated with miscarriage. These findings underscored the important roles of the CTLA-4 and Tim-3 pathways in regulating dCD4+T cells function and maintaining normal pregnancy. Our study also emphasized the importance of careful consideration of reproductive safety when choosing immune checkpoint blockade therapies in real world clinical care.
RETRACTED ARTICLE: Role of the P2X7 receptor in inflammation-mediated changes in the osteogenesis of periodontal ligament stem cells
Authors: Xu Xin-Yue , He Xiao-Tao , Wang Jia , Li Xuan , Xia Yu , Tan Yi-Zhou , Chen Fa-Ming 
Published: January 2019

AbstractAccumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions. Gene-modified PDLSCs were used to further examine the role of P2X7R and the signaling pathway underlying P2X7R-enhanced osteogenesis. We found that inflammatory conditions decreased P2X7R expression in PDLSCs and reduced osteogenesis in these cells. In addition, activation of P2X7R by BzATP or overexpression of P2X7R via gene transduction reversed the inflammation-mediated decrease in PDLSC osteogenic differentiation. When selected osteogenesis-related signaling molecules were screened, the PI3K-AKT-mTOR pathway was identified as potentially involved in P2X7R-enhanced PDLSC osteogenesis. Our data reveal a crucial role for P2X7R in PDLSC osteogenesis under inflammatory conditions, suggesting a new therapeutic target to reverse or rescue inflammation-mediated changes in PDLSCs for future mainstream therapeutic uses.
Argonaute 2 drives miR-145-5p-dependent gene expression program in breast cancer cells
Authors: Bellissimo Teresa , Tito Claudia , Ganci Federica , Sacconi Andrea , Masciarelli Silvia , Di Martino Giuseppe , Porta Natale , Cirenza Mirko , Sorci Melissa , De Angelis Luciana , Rosa Paolo , Calogero Antonella , Fatica Alessandro , Petrozza Vincenzo , Fontemaggi Giulia , Blandino Giovanni , Fazi Francesco 
Published: January 2019

AbstractTo perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1–4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven’t been clearly established. In this study, we investigated the contribution of Ago2, the only human Ago protein endowed with nuclease activity, to the function of tumor-suppressor miR-145-5p in breast cancer (BC). We show that miR-145-5p and Ago2 protein are concomitantly downregulated in BC tissues and that restoration of miR-145-5p expression in BC cells leads to Ago2 protein induction through the loosening of Ago2 mRNA translational repression. Functionally, miR-145-5p exerts its inhibitory activity on cell migration only in presence of Ago2, while, upon Ago2 depletion, we observed increased miR-145/Ago1 complex and enhanced cell motility. Profiling by microarray of miR-145-5p target mRNAs, in BC cells depleted or not of Ago2, revealed that miR-145-5p drives Ago2-dependent and -independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity.
Erythropoietin inhibits chemotherapy-induced cell death and promotes a senescence-like state in leukemia cells
Authors: Pham Thuc-Nghi Duc , Ma Weili , Miller David , Kazakova Lidia , Benchimol Samuel 
Published: January 2019

AbstractThere are conflicting reports on the adverse effects of erythropoietin (EPO) for the management of cancer-associated anemia. The recognition that erythropoietin receptors (EPORs) are expressed outside the erythroid lineage and concerns that erythropoiesis-stimulating agents (ESAs) may cause tumors to grow and increase the risk of venous thromboembolism have resulted in substantially fewer cancer patients receiving ESA therapy to manage myelosuppressive chemotherapy. In this study, we found that EPO suppresses p53-dependent apoptosis induced by genotoxic (daunorubicin, doxorubicin, and γ-radiation) and non-genotoxic (nutlin-3a) agents and induces a senescence-like state in myeloid leukemia cells. EPO interferes with stress-dependent Mdm2 downregulation and leads to the destabilization of p53 protein. EPO selectively modulates the expression of p53 target genes in response to DNA damage preventing the induction of a number of noncoding RNAs (ncRNAs) previously associated with p53-dependent apoptosis. EPO also enhances the expression of the cyclin-dependent kinase inhibitor p21WAF1 and promotes recruitment of p53 to the p21 promoter. In addition, EPO antagonizes Mcl-1 protein degradation in daunorubicin-treated cells. Hence, EPO signaling targets Mcl-1 expression and the p53-Mdm2 network to promote tumor cell survival.
Novel mutations in the RS1 gene in Japanese patients with X-linked congenital retinoschisis
Authors: Kondo Hiroyuki , Oku Kazuma , Katagiri Satoshi , Hayashi Takaaki , Nakano Tadashi , Iwata Akiko , Kuniyoshi Kazuki , Kusaka Shunji , Hiyoshi Atsushi , Uchio Eiichi , Kondo Mineo , Oishi Noriko , Kameya Shuhei , Mizota Atsushi , Naoi Nobuhisa , Ueno Shinji , Terasaki Hiroko , Morimoto Takeshi , Iwaki Masayoshi , Yoshitake Kazutoshi , Iejima Daisuke , Fujinami Kaoru , Tsunoda Kazushige , Shinoda Kei , Iwata Takeshi 
Published: January 2019

AbstractX-linked congenital retinoschisis (XLRS) is an inherited retinal disorder characterized by reduced central vision and schisis of the macula and peripheral retina. XLRS is caused by mutations in the RS1 gene. We have identified 37 different mutations in the RS1 gene, including 12 novel mutations, in 67 Japanese patients from 56 XLRS families. We present clinical features of these patients in relation to the associated mutations.
Expression of novel long noncoding RNAs defines virus-specific effector and memory CD8+ T cells
Authors: Hudson William H. , Prokhnevska Nataliya , Gensheimer Julia , Akondy Rama , McGuire Donald J. , Ahmed Rafi , Kissick Haydn T. 
Published: January 2019

AbstractIn response to viral infection, CD8+ T cells undergo expansion and differentiate into distinct classes of effector cells. After clearance of the virus, a small population of long-lived memory cells persists. Comprehensive studies have defined the protein-coding transcriptional changes associated with this process. Here we expand on this prior work by performing RNA-sequencing to identify changes in long noncoding RNA (lncRNA) expression in human and mouse CD8+ T cells responding to viral infection. We identify hundreds of unannotated lncRNAs and show that expression profiles of both known and novel lncRNAs are sufficient to define naive, effector, and memory CD8+ T cell subsets, implying that they may be involved in fate decisions during antigen-driven differentiation. Additionally, in comparing mouse and human lncRNA expression, we find that lncRNAs with conserved sequence undergo similar changes in expression in the two species, suggesting an evolutionarily conserved role for lncRNAs during CD8+ T cell differentiation.
Genome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis
Authors: Li Yuan , Metcalf Benjamin J. , Chochua Sopio , Li Zhongya , Walker Hollis , Tran Theresa , Hawkins Paulina A. , Gierke Ryan , Pilishvili Tamara , McGee Lesley , Beall Bernard W. 
Published: January 2019

AbstractBacterial mutations predisposing pneumococcus to causing meningitis, a more severe form of invasive pneumococcal disease (IPD), are largely unknown. Knowledge of such mutations may improve our understanding of pathogenesis and inform preventive strategies. Here we report a pneumococcal pbp1b gene mutation (pbp1bA641C causing N214T change in PBP1b transglycosylase domain) that is associated with meningitis in an exploratory cohort of IPD patients (n = 2054, p = 6.8 × 10−6), in an independent confirmatory cohort (n = 2518, p = 2.3 × 10−6), and in a combined analysis (n = 4572, p = 3.0 × 10−10). Patients infected by the pbp1b641C genotype pneumococci show 2.8-fold odds (95% CI 1.7 to 4.8) of meningitis compared to those infected by non-pbp1b641C pneumococci, after controlling for pneumococcal serotype, antibiotic resistance, and patient age. The pbp1bA641C change results in longer time needed for bacterial killing by antibiotic treatment and shows evidence of being under positive selection. Thus, a pneumococcal mutation conferring increased antibiotic tolerance is associated with meningitis among IPD patients.
The evolution of sex determination associated with a chromosomal inversion
Authors: Natri Heini M. , Merilä Juha , Shikano Takahito 
Published: January 2019

AbstractSex determination is a fundamentally important and highly diversified biological process, yet the mechanisms behind the origin of this diversity are mostly unknown. Here we suggest that the evolution of sex determination systems can be driven by a chromosomal inversion. We show that an XY system evolved recently in particular nine-spined stickleback (Pungitius pungitius) populations, which arose from ancient hybridization between two divergent lineages. Our phylogenetic and genetic mapping analyses indicate that the XY system is formed in a large inversion that is associated with hybrid sterility between the divergent lineages. We suggest that a new male-determining gene evolved in the inversion in response to selection against impaired male fertility in a hybridized population. Given that inversions are often associated with hybrid incompatibility in animals and plants, they might frequently contribute to the diversification of sex determination systems.
A micro-dispenser for long-term storage and controlled release of liquids
Authors: Kazemzadeh Amin , Eriksson Anders , Madou Marc , Russom Aman 
Published: January 2019

AbstractThe success of lab-on-a-chip systems may depend on a low-cost device that incorporates on-chip storage and fluidic operations. To date many different methods have been developed that cope separately with on-chip storage and fluidic operations e.g., hydrophobic and capillary valves pneumatic pumping and blister storage packages. The blister packages seem difficult to miniaturize and none of the existing liquid handling techniques despite their variety are capable of proportional repeatable dispensing. We report here on an inexpensive robust and scalable micro-dispenser that incorporates long-term storage and aliquoting of reagents on different microfluidics platforms. It provides long-term shelf-life for different liquids enables precise dispensing on lab-on-a-disc platforms and less accurate but proportional dispensing when operated by finger pressure. Based on this technology we introduce a method for automation of blood plasma separation and multi-step bioassay procedures. This micro-dispenser intends to facilitate affordable portable diagnostic devices and accelerate the commercialization of lab-on-a-chip devices.
Reconfigurable shape-morphing dielectric elastomers using spatially varying electric fields
Authors: Hajiesmaili Ehsan , Clarke David R. 
Published: January 2019

AbstractExceptionally large strains can be produced in soft elastomers by the application of an electric field and the strains can be exploited for a variety of novel actuators, such as tunable lenses and tactile actuators. However, shape morphing with dielectric elastomers has not been possible since no generalizable method for changing their Gaussian curvature has been devised. Here it is shown that this fundamental limitation can be lifted by introducing internal, spatially varying electric fields through a layer-by-layer fabrication method incorporating shaped, carbon-nanotubes-based electrodes between thin elastomer sheets. To illustrate the potential of the method, voltage-tunable negative and positive Gaussian curvatures shapes are produced. Furthermore, by applying voltages to different sets of internal electrodes, the shapes can be re-configured. All the shape changes are reversible when the voltage is removed.
Publisher Correction: A downy mildew effector evades recognition by polymorphism of expression and subcellular localization
Authors: Asai Shuta , Furzer Oliver J. , Cevik Volkan , Kim Dae Sung , Ishaque Naveed , Goritschnig Sandra , Staskawicz Brian J. , Shirasu Ken , Jones Jonathan D. G. 
Published: January 2019

The original version of this article contained an error in the author affiliations. Oliver J. Furzer was incorrectly associated with Department of Plant Sciences, College of Life Sciences, Wuhan University, 430072, Wuhan, China.This has now been corrected in the HTML version of the article. The PDF version of the article was correct at the time of publication.Furthermore, the original version of this article stated that correspondence and requests for materials should be addressed to Heidelberg.Center.for.Personalized.Oncology, DKFZ-HIPO, DKFZ, Heidelberg 69120Germany S.A. (email: shuta.asai@riken.jp) or to J.D.G.J. (email: jonathan.jones@tsl.ac.uk). The words “Heidelberg.Center.for.Personalized.Oncology, DKFZ-HIPO, DKFZ, Heidelberg 69120Germany” were introduced inadvertently.This has now been corrected in the PDF version of the article. The HTML version of the article was correct at the time of publication.
Theoretical description and experimental simulation of quantum entanglement near open time-like curves via pseudo-density operators
Authors: Marletto Chiara , Vedral Vlatko , Virzì Salvatore , Rebufello Enrico , Avella Alessio , Piacentini Fabrizio , Gramegna Marco , Degiovanni Ivo Pietro , Genovese Marco 
Published: January 2019

AbstractClosed timelike curves are striking predictions of general relativity allowing for time-travel. They are afflicted by notorious causality issues (e.g. grandfather’s paradox). Quantum models where a qubit travels back in time solve these problems, at the cost of violating quantum theory’s linearity—leading e.g. to universal quantum cloning. Interestingly, linearity is violated even by open timelike curves (OTCs), where the qubit does not interact with its past copy, but is initially entangled with another qubit. Non-linear dynamics is needed to avoid violating entanglement monogamy. Here we propose an alternative approach to OTCs, allowing for monogamy violations. Specifically, we describe the qubit in the OTC via a pseudo-density operator—a unified descriptor of both temporal and spatial correlations. We also simulate the monogamy violation with polarization-entangled photons, providing a pseudo-density operator quantum tomography. Remarkably, our proposal applies to any space-time correlations violating entanglement monogamy, such as those arising in black holes.
Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis
Authors: Yermalovich Alena V. , Osborne Jihan K. , Sousa Patricia , Han Areum , Kinney Melissa A. , Chen Michael J. , Robinton Daisy A. , Montie Helen , Pearson Dan S. , Wilson Sean B. , Combes Alexander N. , Little Melissa H. , Daley George Q. 
Published: January 2019

AbstractIn humans and in mice the formation of nephrons during embryonic development reaches completion near the end of gestation, after which no new nephrons are formed. The final nephron complement can vary 10-fold, with reduced nephron number predisposing individuals to hypertension, renal, and cardiovascular diseases in later life. While the heterochronic genes lin28 and let-7 are well-established regulators of developmental timing in invertebrates, their role in mammalian organogenesis is not fully understood. Here we report that the Lin28b/let-7 axis controls the duration of kidney development in mice. Suppression of let-7 miRNAs, directly or via the transient overexpression of LIN28B, can prolong nephrogenesis and enhance kidney function potentially via upregulation of the Igf2/H19 locus. In contrast, kidney-specific loss of Lin28b impairs renal development. Our study reveals mechanisms regulating persistence of nephrogenic mesenchyme and provides a rationale for therapies aimed at increasing nephron mass.
Self-assembly of fractal liquid crystal colloids
Authors: Solodkov Nikita V. , Shim Jung-uk , Jones J. Cliff 
Published: January 2019

AbstractNematic liquid crystals are anisotropic fluids that self-assemble into vector fields, which are governed by geometrical and topological laws. Consequently, particulate or droplet inclusions self-assemble in nematic domains through a balance of topological defects. Here, we use double emulsions of water droplets inside radial nematic liquid crystal droplets to form various structures, ranging from linear chains to three-dimensional fractal structures. The system is modeled as a formation of satellite droplets, distributed around a larger, central core droplet and we extend the problem to explain the formation of fractal structures. We show that a distribution of droplet sizes plays a key role in determining the symmetry properties of the resulting geometric structures. The results are relevant to a variety of inclusions, ranging from colloids suspensions to multi-emulsion systems. Such systems have potential applications for novel switchable photonic structures as well as providing wider insights into the packing of self-assembled structures.
Far-field acoustic subwavelength imaging and edge detection based on spatial filtering and wave vector conversion
Authors: Ma Chu , Kim Seok , Fang Nicholas X. 
Published: January 2019

AbstractThe resolution of acoustic imaging suffers from diffraction limit due to the loss of evanescent field that carries subwavelength information. Most of the current methods for overcoming the diffraction limit in acoustics still operate in the near-field of the object. Here we demonstrate the design and experimental realization of an acoustic far-field subwavelength imaging system. Our system is based on wave vector filtering and conversion with a transmitter at the near-field and a spatially symmetrical receiver at the far-field. By tuning geometric parameters of the transmitting/receiving pair, different spatial frequency bands can be separated and projected to the far-field. Furthermore, far-field imaging and edge detection of subwavelength objects are experimentally demonstrated. The proposed system brings new possibilities for far-field subwavelength wave manipulation, which can be further applied to medical imaging, nondestructive testing, and acoustic communication.
Enhanced nematic fluctuations near an antiferromagnetic Mott insulator and possible application to high-Tc cuprates
Authors: Orth Peter P. , Jeevanesan Bhilahari , Fernandes Rafael M. , Schmalian Jörg 
Published: January 2019

AbstractMotivated by the widespread experimental observations of nematicity in strongly underdoped cuprate superconductors, we investigate the possibility of enhanced nematic fluctuations in the vicinity of a Mott insulator that displays Néel-type antiferromagnetic order. By performing a strong-coupling expansion of an effective model that contains both Cu-d and O-p orbitals on the square lattice, we demonstrate that quadrupolar fluctuations in the p-orbitals inevitably generate a biquadratic coupling between the spins of the d-orbitals. The key point revealed by our classical Monte-Carlo simulations and large-N calculations is that the biquadratic term favors local stripe-like magnetic fluctuations, which result in an enhanced nematic susceptibility that onsets at a temperature scale determined by the effective Heisenberg exchange J. We discuss the impact of this type of nematic order on the magnetic spectrum and outline possible implications on our understanding of nematicity in the cuprates.