bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of lncRNA MIR222HG co-transcribed from the miR-221/222 gene promoter facilitates the development of castration-resistant prostate cancer
Authors: Sun Tong , Du Shin-Yi , Armenia Joshua , Qu Fangfang , Fan Jingyu , Wang Xiaodong , Fei Teng , Komura Kazumasa , Liu Shirley X. , Lee Gwo-Shu Mary , Kantoff Philip W 
Published: March 2018

AbstractMechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222. Upon promoter activation, a set of polyadenylated long non-coding RNA (lncRNA) MIR222HGs was transcribed from this promoter region. Over-expression of these MIR222HGs increased androgen-independent cell growth and repressed the expression of androgen receptor-regulated dihydrotestosterone (DHT)-induced KLK3, TMPRSS2, and FKBP5 in HSPC LNCaP cells, hallmarks of the CRPC phenotype. Clinically, increased expression of MIR222HG is associated with PCa progression to CRPC. In primary tumors, expression levels of MIR222HG and miR-221/222 inversely correlate with Gleason score and androgen receptor (AR) pathway activity. Interestingly, MIR222HG is Argonaute 2-bound and its expression is Dicer 1-dependent, suggesting its functional association with the RNA-induced silencing complex. Further studies led to the hypothesis that MIR222HG may potentially affect miR-mediated expression silencing, subsequently leading to AR reprogramming. Our study highlights an essential role of a non-coding RNA in CRPC development and that differential activation of a single promoter can up-regulate two different types of non-coding RNAs, miR-221/222 and lncRNA MIR222HG, in CRPC. Additionally, this study reveals a novel function of lncRNAs as a modulator of Argonaute-mediated RNA-induced silencing complex.
Bipolar disorder in youth is associated with increased levels of vitamin D-binding protein
Authors: Petrov Brawnie , Aldoori Ayat , James Cindy , Yang Kefeng , Algorta Guillermo Perez , Lee Aejin , Zhang Liwen , Lin Tao , Awadhi Reem Al , Parquette Jonathan R. , Samogyi Arpad , Arnold L. Eugene , Fristad Mary A. , Gracious Barbara , Ziouzenkova Ouliana 
Published: March 2018

AbstractGenetic, dietary, and inflammatory factors contribute to the etiology of major mood disorders (MMD), thus impeding the identification of specific biomarkers to assist in diagnosis and treatment. We tested association of vitamin D and inflammatory markers in 36 adolescents with bipolar disorder (BD) and major depressive disorder (MDD) forms of MMD and without MMD (non-mood control). We also assessed the overall level of inflammation using a cell-based reporter assay for nuclear factor kappa-B (NFκB) activation and measuring antibodies to oxidized LDL. We found that these factors were similar between non-mood and MMD youth. To identify potential biomarkers, we developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFβ). We discovered that a homolog of GMFβ in human plasma is vitamin D-binding protein (DBP) and validated this finding using immunoprecipitation with anti-DBP antibodies and mass spectrometry/sequencing analysis. We quantified DBP levels in participants by western blot. DBP levels in BD participants were significantly higher (136%) than in participants without MMD (100%). The increase in DBP levels in MDD participants (121.1%) was not statistically different from these groups. The DBP responds early to cellular damage by binding of structural proteins and activating inflammatory cells. A product of enzymatic cleavage of DBP has been described as macrophage-activating factor. Circulating DBP is comprised of heterogenous high and low molecular fractions that are only partially recognized by mono- and polyclonal ELISA and are not suitable for the quantitative comparison of DBP in non-mood and MDD participants. Our data suggest DBP as a marker candidate of BD warranting its validation in a larger cohort of adolescent and adult MMD patients.
Phenotypic and genetic analysis of cognitive performance in Major Depressive Disorder in the Generation Scotland: Scottish Family Health Study
Authors: Meijsen Joeri J. , Campbell Archie , Hayward Caroline , Porteous David J. , Deary Ian J. , Marioni Riccardo E. , Nicodemus Kristin K. 
Published: March 2018

AbstractLower performances in cognitive ability in individuals with Major Depressive Disorder (MDD) have been observed on multiple occasions. Understanding cognitive performance in MDD could provide a wider insight in the aetiology of MDD as a whole. Using a large, well characterised cohort (N = 7012), we tested for: differences in cognitive performance by MDD status and a gene (single SNP or polygenic score) by MDD interaction effect on cognitive performance. Linear regression was used to assess the association between cognitive performance and MDD status in a case-control, single-episode–recurrent MDD and control-recurrent MDD study design. Test scores on verbal declarative memory, executive functioning, vocabulary, and processing speed were examined. Cognitive performance measures showing a significant difference between groups were subsequently analysed for genetic associations. Those with recurrent MDD have lower processing speed versus controls and single-episode MDD (β = −2.44, p = 3.6 × 10−04; β = -2.86, p = 1.8 × 10−03, respectively). There were significantly higher vocabulary scores in MDD cases versus controls (β = 0.79, p = 2.0 × 10−06), and for recurrent MDD versus controls (β = 0.95, p = 5.8 × 10−05). Observed differences could not be linked to significant single-locus associations. Polygenic scores created from a processing speed meta-analysis GWAS explained 1% of variation in processing speed performance in the single-episode versus recurrent MDD study (p = 1.7 × 10−03) and 0.5% of variation in the control versus recurrent MDD study (p = 1.6 × 10−10). Individuals with recurrent MDD showed lower processing speed and executive function while showing higher vocabulary performance. Within MDD, persons with recurrent episodes show lower processing speed and executive function scores relative to individuals experiencing a single episode.
miR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-βRI signaling pathway
Authors: Fang Fang , Huang Bangxing , Sun Si , Xiao Man , Guo Jing , Yi Xiaoqing , Cai Jing , Wang Zehua 
Published: March 2018

AbstractHigh-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3′-UTR of transforming growth factor beta receptor I (TGF-βRI) and downregulates TGF-β signaling. The co-transfection of a TGF-βRI expression vector largely restored the inhibition of TGF-β signaling, cell proliferation, migration, and invasion mediated by miR-27a-agomir. Also, miR-27a-agomir slows down the growth of subcutaneous HeLa xenografts and downregulates the TGF-βRI expression and TGF-β signaling in tumor in vivo. Tissue microarray analysis revealed a low miR-27a level in adenocarcinoma cells, but not in squamous cell carcinoma cells, which was negatively associated with TGF-βRI expression. High TGF-βRI correlated with deep stromal invasion and lymph node metastasis. These results suggest that miR-27a acts as a tumor suppressor in cervical cancer, especially in adenocarcinoma, by inhibiting TGF-βRI signaling pathway. Thus, enhancing miR-27a expression and function may be a novel treatment strategy for cervical adenocarcinoma.
Archimedes’ law explains penetration of solids into granular media
Authors: Kang Wenting , Feng Yajie , Liu Caishan , Blumenfeld Raphael 
Published: March 2018

AbstractUnderstanding the response of granular matter to intrusion of solid objects is key to modelling many aspects of behaviour of granular matter, including plastic flow. Here we report a general model for such a quasistatic process. Using a range of experiments, we first show that the relation between the penetration depth and the force resisting it, transiently nonlinear and then linear, is scalable to a universal form. We show that the gradient of the steady-state part, K
ϕ
, depends only on the medium’s internal friction angle, ϕ, and that it is nonlinear in μ = tan ϕ, in contrast to an existing conjecture. We further show that the intrusion of any convex solid shape satisfies a modified Archimedes’ law and use this to: relate the zero-depth intercept of the linear part to K
ϕ
and the intruder’s cross-section; explain the curve’s nonlinear part in terms of the stagnant zone’s development.
Publisher Correction: Beyond a phenomenological description of magnetostriction
Authors: Reid A. H. , Shen X. , Maldonado P. , Chase T. , Jal E. , Granitzka P. W. , Carva K. , Li R. K. , Li J. , Wu L. , Vecchione T. , Liu T. , Chen Z. , Higley D. J. , Hartmann N. , Coffee R. , Wu J. , Dakowski G. L. , Schlotter W. F. , Ohldag H. , Takahashi Y. K. , Mehta V. , Hellwig O. , Fry A. , Zhu Y. , Cao J. , Fullerton E. E. , Stöhr J. , Oppeneer P. M. , Wang X. J. , Dürr H. A. 
Published: March 2018

“The technical support from SLAC Accelerator Directorate, Technology Innovation Directorate, LCLS laser division and Test Facility Division is gratefully acknowledged. We thank S.P. Weathersby, R.K. Jobe, D. McCormick, A. Mitra, S. Carron and J. Corbett for their invaluable help and technical assistance. Research at SLAC was supported through the SIMES Institute which like the LCLS and SSRL user facilities is funded by the Office of Basic Energy Sciences of the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The UED work was performed at SLAC MeV-UED, which is supported in part by the DOE BES SUF Division Accelerator & Detector R&D program, the LCLS Facility, and SLAC under contract Nos. DE-AC02-05-CH11231 and DE-AC02-76SF00515. Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515.”and“Work at BNL was supported by DOE BES Materials Science and Engineering Division under Contract No: DE-AC02-98CH10886. J.C. would like to acknowledge the support from National Science Foundation Grant No. 1207252. E.E.F. would like to acknowledge support from the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES) under Award No. DE-SC0003678.”This has been corrected in both the PDF and HTML versions of the Article.
Continuous-wave highly-efficient low-divergence terahertz wire lasers
Authors: Biasco Simone , Garrasi Katia , Castellano Fabrizio , Li Lianhe , Beere Harvey E. , Ritchie David A. , Linfield Edmund H. , Davies A. Giles , Vitiello Miriam S. 
Published: March 2018

AbstractTerahertz (THz) quantum cascade lasers (QCLs) have undergone rapid development since their demonstration, showing high power, broad-tunability, quantum-limited linewidth, and ultra-broadband gain. Typically, to address applications needs, continuous-wave (CW) operation, low-divergent beam profiles and fine spectral control of the emitted radiation, are required. This, however, is very difficult to achieve in practice. Lithographic patterning has been extensively used to this purpose (via distributed feedback (DFB), photonic crystals or microcavities), to optimize either the beam divergence or the emission frequency, or, both of them simultaneously, in third-order DFBs, via a demanding fabrication procedure that precisely constrains the mode index to 3. Here, we demonstrate wire DFB THz QCLs, in which feedback is provided by a sinusoidal corrugation of the cavity, defining the frequency, while light extraction is ensured by an array of surface holes. This new architecture, extendable to a broad range of far-infrared frequencies, has led to the achievement of low-divergent beams (10°), single-mode emission, high slope efficiencies (250 mW/A), and stable CW operation.
A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
Authors: Ladds Marcus J. G. W. , van Leeuwen Ingeborg M. M. , Drummond Catherine J. , Chu Su , Healy Alan R. , Popova Gergana , Pastor Fernández Andrés , Mollick Tanzina , Darekar Suhas , Sedimbi Saikiran K. , Nekulova Marta , Sachweh Marijke C. C. , Campbell Johanna , Higgins Maureen , Tuck Chloe , Popa Mihaela , Safont Mireia Mayoral , Gelebart Pascal , Fandalyuk Zinayida , Thompson Alastair M. , Svensson Richard , Gustavsson Anna-Lena , Johansson Lars , Färnegårdh Katarina , Yngve Ulrika , Saleh Aljona , Haraldsson Martin , D’Hollander Agathe C. A. , Franco Marcela , Zhao Yan , Håkansson Maria , Walse Björn , Larsson Karin , Peat Emma M. , Pelechano Vicent , Lunec John , Vojtesek Borivoj , Carmena Mar , Earnshaw William C. , McCarthy Anna R. , Westwood Nicholas J. , Arsenian-Henriksson Marie , Lane David P. , Bhatia Ravi , McCormack Emmet , Laín Sonia 
Published: March 2018

AbstractThe development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
Asymmetric adhesion of rod-shaped bacteria controls microcolony morphogenesis
Authors: Duvernoy Marie-Cécilia , Mora Thierry , Ardré Maxime , Croquette Vincent , Bensimon David , Quilliet Catherine , Ghigo Jean-Marc , Balland Martial , Beloin Christophe , Lecuyer Sigolène , Desprat Nicolas 
Published: March 2018

AbstractSurface colonization underpins microbial ecology on terrestrial environments. Although factors that mediate bacteria–substrate adhesion have been extensively studied, their spatiotemporal dynamics during the establishment of microcolonies remains largely unexplored. Here, we use laser ablation and force microscopy to monitor single-cell adhesion during the course of microcolony formation. We find that adhesion forces of the rod-shaped bacteria Escherichia coli and Pseudomonas aeruginosa are polar. This asymmetry induces mechanical tension, and drives daughter cell rearrangements, which eventually determine the shape of the microcolonies. Informed by experimental data, we develop a quantitative model of microcolony morphogenesis that enables the prediction of bacterial adhesion strength from simple time-lapse measurements. Our results demonstrate how patterns of surface colonization derive from the spatial distribution of adhesive factors on the cell envelope.
SUMO targets the APC/C to regulate transition from metaphase to anaphase
Authors: Eifler Karolin , Cuijpers Sabine A. G. , Willemstein Edwin , Raaijmakers Jonne A. , El Atmioui Dris , Ovaa Huib , Medema René H. , Vertegaal Alfred C. O. 
Published: March 2018

AbstractSignal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation is crucial for accurate progression of cells through mitosis and increases APC/C ubiquitylation activity toward a subset of its targets, including the newly identified target KIF18B. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal how SUMO and ubiquitin cooperate to drive mitosis.
A b map implying the first eastern rupture of the Nankai Trough earthquakes
Authors: Nanjo K. Z. , Yoshida A. 
Published: March 2018

AbstractThe Nankai Trough megathrust earthquakes inflicted catastrophic damage on Japanese society and more widely. Most research is aimed at identifying strongly coupled regions that are considered as a major source of future disastrous earthquakes. Here we present a b-value map for the entire Nankai Trough zone. The b value, which represents the rate of occurrence of small earthquakes relative to larger ones, is inversely dependent on differential stresses, and has been used to detect highly stressed areas on fault planes in various tectonic situations. A remarkable finding is that the b value is inversely correlated with the slip-deficit rate (SDR). Moreover, the b value for the areas of high SDR in the eastern part is lower than that in the western part, indicating that differential stress on asperities in the eastern part is higher than that in the western part. This may explain the history of the Nankai Trough earthquakes, in which the eastern part tends to rupture first.
Clathrin-adaptor ratio and membrane tension regulate the flat-to-curved transition of the clathrin coat during endocytosis
Authors: Bucher Delia , Frey Felix , Sochacki Kem A. , Kummer Susann , Bergeest Jan-Philip , Godinez William J. , Kräusslich Hans-Georg , Rohr Karl , Taraska Justin W. , Schwarz Ulrich S. , Boulant Steeve 
Published: March 2018

AbstractAlthough essential for many cellular processes, the sequence of structural and molecular events during clathrin-mediated endocytosis remains elusive. While it was long believed that clathrin-coated pits grow with a constant curvature, it was recently suggested that clathrin first assembles to form flat structures that then bend while maintaining a constant surface area. Here, we combine correlative electron and light microscopy and mathematical growth laws to study the ultrastructural rearrangements of the clathrin coat during endocytosis in BSC-1 mammalian cells. We confirm that clathrin coats initially grow flat and demonstrate that curvature begins when around 70% of the final clathrin content is acquired. We find that this transition is marked by a change in the clathrin to clathrin-adaptor protein AP2 ratio and that membrane tension suppresses this transition. Our results support the notion that BSC-1 mammalian cells dynamically regulate the flat-to-curved transition in clathrin-mediated endocytosis by both biochemical and mechanical factors.
Management of constipation in patients with Parkinson’s disease
Authors: Pedrosa Carrasco Anna J. , Timmermann Lars , Pedrosa David J. 
Published: March 2018

AbstractA considerable body of research has recently emerged around nonmotor symptoms in Parkinson’s disease (PD) and their substantial impact on patients’ well-being. A prominent example is constipation which occurs in up to two thirds of all PD-patients thereby effecting psychological and social distress and consequently reducing quality of life. Despite the significant clinical relevance of constipation, unfortunately little knowledge exists on effective treatments. Therefore this systematic review aims at providing a synopsis on clinical effects and safety of available treatment options for constipation in PD. For this purpose, three electronic databases (MEDLINE, EMBASE, PsycINFO) were searched for experimental and quasi-experimental studies investigating the efficacy/effectiveness of interventions in the management of PD-associated constipation. Besides, adverse events were analyzed as secondary outcome. In total, 18 publications were identified involving 15 different interventions, of which none can be attributed sufficient evidence to derive strong recommendations. Nevertheless, some evidence indicates that dietetic interventions with probiotics and prebiotics may reduce symptom burden while providing a very favorable side-effects profile. Furthermore, the use of lubiprostone, macrogol and in the specific case of isolated or prominent outlet obstruction constipation injections of botulinum neurotoxin A into the puborectal muscles may as well be moderately supported. In summary, too little attention has been paid to treatment options for constipation in PD leaving abundant room for further research addressing this topic.
Population screening and transmission experiments indicate paramyxid-microsporidian co-infection in Echinogammarus marinus represents a non-hyperparasitic relationship between specific parasite strains
Authors: Guler Yasmin , Short Stephen , Green Etxabe Amaia , Kille Peter , Ford Alex T. 
Published: March 2018

AbstractPhylogenetically distant parasites often infect the same host. Indeed, co-infections can occur at levels greater than expected by chance and are sometimes hyperparasitic. The amphipod Echinogammarus marinus presents high levels of co-infection by two intracellular and vertically transmitted parasites, a paramyxid (Paramarteilia sp. Em) and a microsporidian strain (Dictyocoela duebenum Em). This co-infection may be hyperparasitic and result from an exploitative ‘hitchhiking’ or a symbiotic relationship between the parasites. However, the best-studied amphipod species are often collected from contaminated environments and may be immune-compromised. Immune-challenged animals frequently present co-infections and contaminant-exposed amphipods present significantly higher levels of microsporidian infection. This suggests the co-infections in E. marinus may result from contaminant-associated compromised immunity. Inconsistent with hyperparasitism, we find that artificial infections transmit Paramarteilia without microsporidian. Our population surveys reveal the co-infection relationship is geographically widespread but find only chance co-infection between the Paramarteilia and another species of microsporidian, Dictyocoela berillonum. Furthermore, we identify a haplotype of the Paramarteilia that presents no co-infection, even in populations with otherwise high co-infection levels. Overall, our results do not support the compromised-immunity hypothesis but rather that the co-infection of E. marinus, although non-hyperparasitic, results from a relationship between specific Paramarteilia and Dictyocoela duebenum strains.