bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular rheotaxis directs DNA migration and concentration against a pressure-driven flow
Authors: Friedrich Sarah M. , Burke Jeffrey M. , Liu Kelvin J. , Ivory Cornelius F. , Wang Tza-Huei 
Published: October 2017

AbstractIn-line preconcentration techniques are used to improve the sensitivity of microfluidic DNA analysis platforms. The most common methods are electrokinetic and require an externally applied electric field. Here we describe a microfluidic DNA preconcentration technique that does not require an external field. Instead, pressure-driven flow from a fluid-filled microcapillary into a lower ionic strength DNA sample reservoir induces spontaneous DNA migration against the direction of flow. This migratory phenomenon that we call Molecular Rheotaxis initiates in seconds and results in a concentrated DNA bolus at the capillary orifice. We demonstrate the ease with which this concentration method can be integrated into a microfluidic total analysis system composed of in-line DNA preconcentration, size separation, and single-molecule detection. Paired experimental and numerical simulation results are used to delineate the parameters required to induce Molecular Rheotaxis, elucidate the underlying mechanism, and optimize conditions to achieve DNA concentration factors exceeding 10,000 fold.
Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer
Authors: Samaranayake Govindi J. , Troccoli Clara I. , Huynh Mai , Lyles Rolando D. Z. , Kage Karen , Win Andrew , Lakshmanan Vishalakshi , Kwon Deukwoo , Ban Yuguang , Chen Steven Xi , Zarco Enrique Rodriguez , Jorda Merce , Burnstein Kerry L. , Rai Priyamvada 
Published: October 2017

AbstractAndrogen deprivation (AD) therapy failure leads to terminal and incurable castration-resistant prostate cancer (CRPC). We show that the redox-protective protein thioredoxin-1 (TRX1) increases with prostate cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1. TRX1 inhibition via shRNA or a phase I-approved inhibitor, PX-12 (untested in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-dependent counterparts. TRX1 inhibition elevates reactive oxygen species (ROS), p53 levels and cell death in androgen-deprived CRPC cells. Unexpectedly, TRX1 inhibition also elevates androgen receptor (AR) levels under AD, and AR depletion mitigates both TRX1 inhibition-mediated ROS production and cell death, suggesting that AD-resistant AR expression in CRPC induces redox vulnerability. In vivo TRX1 inhibition via shRNA or PX-12 reverses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation under systemic AD. Thus, TRX1 is an actionable CRPC therapeutic target through its protection against AR-induced redox stress.
Transformation of doped graphite into cluster-encapsulated fullerene cages
Authors: Mulet-Gas Marc , Abella Laura , Cerón Maira R. , Castro Edison , Marshall Alan G. , Rodríguez-Fortea Antonio , Echegoyen Luis , Poblet Josep M. , Dunk Paul W. 
Published: October 2017

AbstractAn ultimate goal in carbon nanoscience is to decipher formation mechanisms of highly ordered systems. Here, we disclose chemical processes that result in formation of high-symmetry clusterfullerenes, which attract interest for use in applications that span biomedicine to molecular electronics. The conversion of doped graphite into a C80 cage is shown to occur through bottom-up self-assembly reactions. Unlike conventional forms of fullerene, the iconic Buckminsterfullerene cage, Ih-C60, is entirely avoided in the bottom-up formation mechanism to afford synthesis of group 3-based metallic nitride clusterfullerenes. The effects of structural motifs and cluster–cage interactions on formation of compounds in the solvent-extractable C70–C100 region are determined by in situ studies of defined clusterfullerenes under typical synthetic conditions. This work establishes the molecular origin and mechanism that underlie formation of unique carbon cage materials, which may be used as a benchmark to guide future nanocarbon explorations.
Hierarchical self-entangled carbon nanotube tube networks
Authors: Schütt Fabian , Signetti Stefano , Krüger Helge , Röder Sarah , Smazna Daria , Kaps Sören , Gorb Stanislav N. , Mishra Yogendra Kumar , Pugno Nicola M. , Adelung Rainer 
Published: October 2017

AbstractThree-dimensional (3D) assemblies based on carbon nanomaterials still lag behind their individual one-dimensional building blocks in terms of mechanical and electrical properties. Here we demonstrate a simple strategy for the fabrication of an open porous 3D self-organized double-hierarchical carbon nanotube tube structure with properties advantageous to those existing so far. Even though no additional crosslinking exists between the individual nanotubes, a high reinforcement effect in compression and tensile characteristics is achieved by the formation of self-entangled carbon nanotube (CNT) networks in all three dimensions, employing the CNTs in their high tensile properties. Additionally, the tubular structure causes a self-enhancing effect in conductivity when employed in a 3D stretchable conductor, together with a high conductivity at low CNT concentrations. This strategy allows for an easy combination of different kinds of low-dimensional nanomaterials in a tube-shaped 3D structure, enabling the fabrication of multifunctional inorganic-carbon-polymer hybrid 3D materials.
Diversity oriented biosynthesis via accelerated evolution of modular gene clusters
Authors: Wlodek Aleksandra , Kendrew Steve G. , Coates Nigel J. , Hold Adam , Pogwizd Joanna , Rudder Steven , Sheehan Lesley S. , Higginbotham Sarah J. , Stanley-Smith Anna E. , Warneck Tony , Nur-E-Alam Mohammad , Radzom Markus , Martin Christine J. , Overvoorde Lois , Samborskyy Markiyan , Alt Silke , Heine Daniel , Carter Guy T. , Graziani Edmund I. , Koehn Frank E. , McDonald Leonard , Alanine Alexander , Rodríguez Sarmiento Rosa María , Chao Suzan Keen , Ratni Hasane , Steward Lucinda , Norville Isobel H. , Sarkar-Tyson Mitali , Moss Steven J. , Leadlay Peter F. , Wilkinson Barrie , Gregory Matthew A. 
Published: October 2017

AbstractErythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular polyketide synthase multienzymes by an assembly-line process in which each module of enzymes in turn specifies attachment of a particular chemical unit. Although polyketide synthase encoding genes have been successfully engineered to produce novel analogues, the process can be relatively slow, inefficient, and frequently low-yielding. We now describe a method for rapidly recombining polyketide synthase gene clusters to replace, add or remove modules that, with high frequency, generates diverse and highly productive assembly lines. The method is exemplified in the rapamycin biosynthetic gene cluster where, in a single experiment, multiple strains were isolated producing new members of a rapamycin-related family of polyketides. The process mimics, but significantly accelerates, a plausible mechanism of natural evolution for modular polyketide synthases. Detailed sequence analysis of the recombinant genes provides unique insight into the design principles for constructing useful synthetic assembly-line multienzymes.
Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors
Authors: Cheng Jiqiu , Demeulemeester Jonas , Wedge David C. , Vollan Hans Kristian M. , Pitt Jason J. , Russnes Hege G. , Pandey Bina P. , Nilsen Gro , Nord Silje , Bignell Graham R. , White Kevin P. , Børresen-Dale Anne-Lise , Campbell Peter J. , Kristensen Vessela N. , Stratton Michael R. , Lingjærde Ole Christian , Moreau Yves , Van Loo Peter 
Published: October 2017

AbstractHomozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis.
Nonlinear photon-atom coupling with 4Pi microscopy
Authors: Chin Yue-Sum , Steiner Matthias , Kurtsiefer Christian 
Published: October 2017

AbstractImplementing nonlinear interactions between single photons and single atoms is at the forefront of optical physics. Motivated by the prospects of deterministic all-optical quantum logic, many efforts are currently underway to find suitable experimental techniques. Focusing the incident photons onto the atom with a lens yielded promising results, but is limited by diffraction to moderate interaction strengths. However, techniques to exceed the diffraction limit are known from high-resolution imaging. Here we adapt a super-resolution imaging technique, 4Pi microscopy, to efficiently couple light to a single atom. We observe 36.6(3)% extinction of the incident field, and a modified photon statistics of the transmitted field–indicating nonlinear interaction at the single-photon level. Our results pave the way to few-photon nonlinear optics with individual atoms in free space.
Direct Evidence of Adult Aedes albopictus Dispersal by Car
Authors: Eritja Roger , Palmer John R. B. , Roiz David , Sanpera-Calbet Isis , Bartumeus Frederic 
Published: October 2017

AbstractWhereas the Asian tiger mosquito (Aedes albopictus) has low active dispersal capabilities, its worldwide colonization has been rapid. Indirect evidence and informal reports have long implicated passive transportation in cars, but this has not previously been studied systematically given the difficulties of real-time roadside surveys. Here we report the first sampling study confirming that adult tiger mosquitoes travel with humans in cars and enabling us to estimate the frequency of these events. We combine the results with citizen science data to model the car-facilitated dispersal of Aedes albopictus at a nationwide level. During the summer of 2015, we sampled 770 cars in north-eastern Spain, discovering 4 adult female tiger mosquitoes that had entered cars prior to sampling. Our Bayesian model suggests that of the 6.5 million daily car trips in the Barcelona metropolitan area, between 13,000 and 71,500 facilitate tiger mosquito movement, and that Barcelona is the largest source of inter-province tiger mosquito transfers in Spain. Our results are supported by expert-validated citizen science data, and will contribute to better understanding the tiger mosquito’s invasion process and ultimately lead to more effective vector control strategies.
Effects of strength training and raloxifene on femoral neck metabolism and microarchitecture of aging female Wistar rats
Authors: Stringhetta-Garcia Camila Tami , Morais Samuel Rodrigues Lourenço , Fernandes Fernanda , Perez-Ueno Melise Jacon , Almeida Ricardo de Paula , Louzada Mário Jefferson Quirino , Chaves-Neto Antonio Hernandes , Ervolino Edilson , Dornelles Rita Cássia Menegati 
Published: October 2017

AbstractThe aim of this study was to prevent female osteoporosis using strength training (ST), raloxifene (Ral) or a combination of ST plus Ral during the natural female aging process, specifically in the periestropause period. For a total of 120 days, aging female Wistar rats at 18-21 months of age performed ST on a ladder three times per week, and Ral was administered daily by gavage (1 mg/kg/day). Bone microarchitecture, areal bone mineral density, bone strength of the femoral neck, immunohistochemistry, osteoclast and osteoblast surface were assessed. We found that the treatments modulate the bone remodeling cycle in different ways. Both ST and Ral treatment resulted in improved bone microarchitecture in the femoral neck of rats in late periestropause. However, only ST improved cortical microarchitecture and bone strength in the femoral neck. Thus, we suggest that performing ST during the late period of periestropause is a valid intervention to prevent age-associated osteoporosis in females.
Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule
Authors: Ferrandez Yann , Zhang Wenhua , Peurois François , Akendengué Lurlène , Blangy Anne , Zeghouf Mahel , Cherfils Jacqueline 
Published: October 2017

AbstractRac small GTPases and their GEFs of the DOCK family are pivotal checkpoints in development, autoimmunity and bone homeostasis, and their abnormal regulation is associated to diverse pathologies. Small molecules that inhibit their activities are therefore needed to investigate their functions. Here, we characterized the mechanism of inhibition of human DOCK5 by C21, a small molecule that inhibits mouse Dock5 in cells and blocks bone degradation in mice models of osteoporosis. We showed that the catalytic DHR2 domain of DOCK5 has a high basal GEF activity in the absence of membranes which is not regulated by a simple feedback loop. C21 blocks this activity in a non-competitive manner and is specific for DOCK5. In contrast, another Dock inhibitor, CPYPP, inhibits both DOCK5 and an unrelated GEF, Trio. To gain insight into structural features of the inhibitory mechanism of C21, we used SAXS analysis of DOCK5DHR2 and crystallographic analysis of unbound Rac1-GDP. Together, these data suggest that C21 takes advantage of intramolecular dynamics of DOCK5 and Rac1 to remodel the complex into an unproductive conformation. Based on this allosteric mechanism, we propose that diversion of intramolecular dynamics is a potent mechanism for the inhibition of multidomain regulators of small GTPases.
Enhanced flux pinning in YBCO multilayer films with BCO nanodots and segmented BZO nanorods
Authors: Malmivirta Mika , Rijckaert Hannes , Paasonen Ville , Huhtinen Hannu , Hynninen Teemu , Jha Rajveer , Awana Veerpal Singh , Van Driessche Isabel , Paturi Petriina 
Published: October 2017

AbstractThe flux pinning properties of the high temperature superconductor YBa2Cu3O7−δ
(YBCO) have been conventionally improved by creating both columnar and dot-like pinning centres into the YBCO matrix. To study the effects of differently doped multilayer structures on pinning, several samples consisting of a multiple number of individually BaZrO3 (BZO) and BaCeO3 (BCO) doped YBCO layers were fabricated. In the YBCO matrix, BZO forms columnar and BCO dot-like defects. The multilayer structure improves pinning capability throughout the whole angular range, giving rise to a high critical current density, Jc. However, the BZO doped monolayer reference still has the most isotropic Jc. Even though BZO forms nanorods, in this work the samples with multiple thin layers do not exhibit a c axis peak in the angular dependence of Jc. The angular dependencies and the approximately correct magnitude of Jc were also verified using a molecular dynamics simulation.
Modes of carbon fixation in an arsenic and CO2-rich shallow hydrothermal ecosystem
Authors: Callac Nolwenn , Posth Nicole R. , Rattray Jayne E. , Yamoah Kweku K. Y. , Wiech Alan , Ivarsson Magnus , Hemmingsson Christoffer , Kilias Stephanos P. , Argyraki Ariadne , Broman Curt , Skogby Henrik , Smittenberg Rienk H. , Fru Ernest Chi 
Published: October 2017

AbstractThe seafloor sediments of Spathi Bay, Milos Island, Greece, are part of the largest arsenic-CO2-rich shallow submarine hydrothermal ecosystem on Earth. Here, white and brown deposits cap chemically distinct sediments with varying hydrothermal influence. All sediments contain abundant genes for autotrophic carbon fixation used in the Calvin-Benson-Bassham (CBB) and reverse tricaboxylic acid (rTCA) cycles. Both forms of RuBisCO, together with ATP citrate lyase genes in the rTCA cycle, increase with distance from the active hydrothermal centres and decrease with sediment depth. Clustering of RuBisCO Form II with a highly prevalent Zetaproteobacteria 16S rRNA gene density infers that iron-oxidizing bacteria contribute significantly to the sediment CBB cycle gene content. Three clusters form from different microbial guilds, each one encompassing one gene involved in CO2 fixation, aside from sulfate reduction. Our study suggests that the microbially mediated CBB cycle drives carbon fixation in the Spathi Bay sediments that are characterized by diffuse hydrothermal activity, high CO2, As emissions and chemically reduced fluids. This study highlights the breadth of conditions influencing the biogeochemistry in shallow CO2-rich hydrothermal systems and the importance of coupling highly specific process indicators to elucidate the complexity of carbon cycling in these ecosystems.
miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
Authors: Wohlfarth Carolin , Schmitteckert Stefanie , Härtle Janina D. , Houghton Lesley A. , Dweep Harsh , Fortea Marina , Assadi Ghazaleh , Braun Alexander , Mederer Tanja , Pöhner Sarina , Becker Philip P. , Fischer Christine , Granzow Martin , Mönnikes Hubert , Mayer Emeran A. , Sayuk Gregory , Boeckxstaens Guy , Wouters Mira M. , Simrén Magnus , Lindberg Greger , Ohlsson Bodil , Schmidt Peter Thelin , Dlugosz Aldona , Agreus Lars , Andreasson Anna , D’Amato Mauro , Burwinkel Barbara , Bermejo Justo Lorenzo , Röth Ralph , Lasitschka Felix , Vicario Maria , Metzger Marco , Santos Javier , Rappold Gudrun A. , Martinez Cristina , Niesler Beate 
Published: October 2017

AbstractIrritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.
The non-invasive exfoliated transcriptome (exfoliome) reflects the tissue-level transcriptome in a mouse model of NSAID enteropathy
Authors: Whitfield-Cargile Canaan M. , Cohen Noah D. , He Kejun , Ivanov Ivan , Goldsby Jennifer S. , Chamoun-Emanuelli Ana , Weeks Brad R. , Davidson Laurie A. , Chapkin Robert S. 
Published: October 2017

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used classes of medications in the world, yet they induce an enteropathy that is associated with high morbidity and mortality. A major limitation to better understanding the pathophysiology and diagnosis of this enteropathy is the difficulty of obtaining information about the primary site of injury, namely the distal small intestine. We investigated the utility of using mRNA from exfoliated cells in stool as a means to surveil the distal small intestine in a murine model of NSAID enteropathy. Specifically, we performed RNA-Seq on exfoliated cells found in feces and compared these data to RNA-Seq from both the small intestinal mucosa and colonic mucosa of healthy control mice or those exhibiting NSAID-induced enteropathy. Global gene expression analysis, data intersection, pathway analysis, and computational approaches including linear discriminant analysis (LDA) and sparse canonical correlation analysis (CCA) were used to assess the inter-relatedness of tissue (invasive) and stool (noninvasive) datasets. These analyses revealed that the exfoliated cell transcriptome closely mirrored the transcriptome of the small intestinal mucosa. Thus, the exfoliome may serve as a non-invasive means of detecting and monitoring NSAID enteropathy (and possibly other gastrointestinal mucosal inflammatory diseases).
Design and Computational Modeling of a Modular, Compliant Robotic Assembly for Human Lumbar Unit and Spinal Cord Assistance
Authors: Agarwal Gunjan , Robertson Matthew A. , Sonar Harshal , Paik Jamie 
Published: October 2017

AbstractWearable soft robotic systems are enabling safer human-robot interaction and are proving to be instrumental for biomedical rehabilitation. In this manuscript, we propose a novel, modular, wearable robotic device for human (lumbar) spine assistance that is developed using vacuum driven, soft pneumatic actuators (V-SPA). The actuators can handle large, repetitive loads efficiently under compression. Computational models to capture the complex non-linear mechanical behavior of individual actuator modules and the integrated assistive device are developed using the finite element method (FEM). The models presented can predict system behavior at large values of mechanical deformations and allow for rapid design iterations. It is shown that a single actuator module can be used to obtain a variety of different motion and force profiles and yield multiple degrees of freedom (DOF) depending on the module loading conditions, resulting in high system versatility and adaptability, and efficient replication of the targeted motion range for the human spinal cord. The efficacy of the finite element model is first validated for a single module using experimental results that include free displacement and blocked-forces. These results are then extended to encompass an extensive investigation of bio-mechanical performance requirements from the module assembly for the human spine-assistive device proposed.