bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extension of human lncRNA transcripts by RACE coupled with long-read high-throughput sequencing (RACE-Seq)
Authors: Lagarde Julien , Uszczynska-Ratajczak Barbara , Santoyo-Lopez Javier , Gonzalez Jose Manuel , Tapanari Electra , Mudge Jonathan M. , Steward Charles A. , Wilming Laurens , Tanzer Andrea , Howald Cédric , Chrast Jacqueline , Vela-Boza Alicia , Rueda Antonio , Lopez-Domingo Francisco J. , Dopazo Joaquin , Reymond Alexandre , Guigó Roderic , Harrow Jennifer 
Published: August 2016

AbstractLong non-coding RNAs (lncRNAs) constitute a large, yet mostly uncharacterized fraction of the mammalian transcriptome. Such characterization requires a comprehensive, high-quality annotation of their gene structure and boundaries, which is currently lacking. Here we describe RACE-Seq, an experimental workflow designed to address this based on RACE (rapid amplification of cDNA ends) and long-read RNA sequencing. We apply RACE-Seq to 398 human lncRNA genes in seven tissues, leading to the discovery of 2,556 on-target, novel transcripts. About 60% of the targeted loci are extended in either 5′ or 3′, often reaching genomic hallmarks of gene boundaries. Analysis of the novel transcripts suggests that lncRNAs are as long, have as many exons and undergo as much alternative splicing as protein-coding genes, contrary to current assumptions. Overall, we show that RACE-Seq is an effective tool to annotate an organism’s deep transcriptome, and compares favourably to other targeted sequencing techniques.
Thermodynamics of freezing and melting
Authors: Pedersen Ulf R. , Costigliola Lorenzo , Bailey Nicholas P. , Schrøder Thomas B. , Dyre Jeppe C. 
Published: August 2016

AbstractAlthough the freezing of liquids and melting of crystals are fundamental for many areas of the sciences, even simple properties like the temperature–pressure relation along the melting line cannot be predicted today. Here we present a theory in which properties of the coexisting crystal and liquid phases at a single thermodynamic state point provide the basis for calculating the pressure, density and entropy of fusion as functions of temperature along the melting line, as well as the variation along this line of the reduced crystalline vibrational mean-square displacement (the Lindemann ratio), and the liquid’s diffusion constant and viscosity. The framework developed, which applies for the sizable class of systems characterized by hidden scale invariance, is validated by computer simulations of the standard 12-6 Lennard-Jones system.
Ubiquity and impact of thin mid-level clouds in the tropics
Authors: Bourgeois Quentin , Ekman Annica M. L. , Igel Matthew R. , Krejci Radovan 
Published: August 2016

AbstractClouds are crucial for Earth’s climate and radiation budget. Great attention has been paid to low, high and vertically thick tropospheric clouds such as stratus, cirrus and deep convective clouds. However, much less is known about tropospheric mid-level clouds as these clouds are challenging to observe in situ and difficult to detect by remote sensing techniques. Here we use Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) satellite observations to show that thin mid-level clouds (TMLCs) are ubiquitous in the tropics. Supported by high-resolution regional model simulations, we find that TMLCs are formed by detrainment from convective clouds near the zero-degree isotherm. Calculations using a radiative transfer model indicate that tropical TMLCs have a cooling effect on climate that could be as large in magnitude as the warming effect of cirrus. We conclude that more effort has to be made to understand TMLCs, as their influence on cloud feedbacks, heat and moisture transport, and climate sensitivity could be substantial.
Volume-wise destruction of the antiferromagnetic Mott insulating state through quantum tuning
Authors: Frandsen Benjamin A. , Liu Lian , Cheung Sky C. , Guguchia Zurab , Khasanov Rustem , Morenzoni Elvezio , Munsie Timothy J. S. , Hallas Alannah M. , Wilson Murray N. , Cai Yipeng , Luke Graeme M. , Chen Bijuan , Li Wenmin , Jin Changqing , Ding Cui , Guo Shengli , Ning Fanlong , Ito Takashi U. , Higemoto Wataru , Billinge Simon J. L. , Sakamoto Shoya , Fujimori Atsushi , Murakami Taito , Kageyama Hiroshi , Alonso Jose Antonio , Kotliar Gabriel , Imada Masatoshi , Uemura Yasutomo J. 
Published: August 2016

AbstractRENiO3 (RE=rare-earth element) and V2O3 are archetypal Mott insulator systems. When tuned by chemical substitution (RENiO3) or pressure (V2O3), they exhibit a quantum phase transition (QPT) between an antiferromagnetic Mott insulating state and a paramagnetic metallic state. Because novel physics often appears near a Mott QPT, the details of this transition, such as whether it is first or second order, are important. Here, we demonstrate through muon spin relaxation/rotation (μSR) experiments that the QPT in RENiO3 and V2O3 is first order: the magnetically ordered volume fraction decreases to zero at the QPT, resulting in a broad region of intrinsic phase separation, while the ordered magnetic moment retains its full value until it is suddenly destroyed at the QPT. These findings bring to light a surprising universality of the pressure-driven Mott transition, revealing the importance of phase separation and calling for further investigation into the nature of quantum fluctuations underlying the transition.
Telomeric RNAs are essential to maintain telomeres
Authors: Montero Juan José , López de Silanes Isabel , Graña Osvaldo , Blasco Maria A. 
Published: August 2016

AbstractTelomeres are transcribed generating long non-coding RNAs known as TERRA. Deciphering the role of TERRA has been one of the unsolved issues of telomere biology in the past decade. This has been, in part, due to lack of knowledge on the TERRA loci, thus preventing functional genetic studies. Here, we describe that long non-coding RNAs with TERRA features are transcribed from the human 20q and Xp subtelomeres. Deletion of the 20q locus by using the CRISPR-Cas9 technology causes a dramatic decrease in TERRA levels, while deletion of the Xp locus does not result in decreased TERRA levels. Strikingly, 20q-TERRA ablation leads to dramatic loss of telomere sequences and the induction of a massive DNA damage response. These findings identify chromosome 20q as a main TERRA locus in human cells and represent the first demonstration in any organism of the essential role of TERRA in the maintenance of telomeres.
Sharing health-related data: a privacy test?
Authors: Dyke Stephanie OM , Dove Edward S , Knoppers Bartha M 
Published: August 2016

AbstractGreater sharing of potentially sensitive data raises important ethical, legal and social issues (ELSI), which risk hindering and even preventing useful data sharing if not properly addressed. One such important issue is respecting the privacy-related interests of individuals whose data are used in genomic research and clinical care. As part of the Global Alliance for Genomics and Health (GA4GH), we examined the ELSI status of health-related data that are typically considered ‘sensitive’ in international policy and data protection laws. We propose that ‘tiered protection’ of such data could be implemented in contexts such as that of the GA4GH Beacon Project to facilitate responsible data sharing. To this end, we discuss a Data Sharing Privacy Test developed to distinguish degrees of sensitivity within categories of data recognised as ‘sensitive’. Based on this, we propose guidance for determining the level of protection when sharing genomic and health-related data for the Beacon Project and in other international data sharing initiatives.
Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown
Authors: Srikar R. , Suresh Dhananjay , Zambre Ajit , Taylor Kristen , Chapman Sarah , Leevy Matthew , Upendran Anandhi , Kannan Raghuraman 
Published: August 2016

AbstractA tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation.
Mussel-inspired Polydopamine-treated Copper Foil as a Current Collector for High-performance Silicon Anodes
Authors: Cho Inseong , Gong Seokhyeon , Song Danoh , Lee Young-Gi , Ryou Myung-Hyun , Lee Yong Min 
Published: August 2016

AbstractA new Cu current collector was prepared by introducing a mussel-inspired polydopamine coating onto a Cu foil surface to improve the electrochemical performance of a Si electrode. The polydopamine coating covalently bonded the polymeric binder (with hydroxyl functional groups) via a condensation reaction. The coating improved the adhesion strength between the Si composite electrode and the Cu current collector (245.5 N m−1, 297.5 N m−1, and 353.2 N m−1 for the Si electrodes based on bare Cu, polydopamine-treated Cu without thermal treatment, and polydopamine-treated Cu with thermal treatment, respectively). We demonstrate that the detachment between the Si composite electrode and the current collector plays an important role in determining the electrochemical performance of the Si electrode. The cycle life and rate capability of the Si electrode improved when the polydopamine surface-treated Cu current collector was used (963.9 mAh g−1, 1361.1 mAh g−1, and 1590.0 mAh g−1 for the Si electrodes based on bare Cu, polydopamine-treated Cu without thermal treatment, and polydopamine-treated Cu with thermal treatment, respectively, at C/2 after 500 cycles).
Synthesis, Biological Evaluation and Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids against Phytopathogenic Fungi
Authors: Jian Weilin , He Daohang , Song Shaoyun 
Published: August 2016

AbstractNatural stilbenes (especially resveratrol) play important roles in plant protection by acting as both constitutive and inducible defenses. However, their exogenous applications on crops as fungicidal agents are challenged by their oxidative degradation and limited availability. In this study, a new class of resveratrol-inspired oxadiazole-stilbene hybrids was synthesized via Wittig-Horner reaction. Bioassay results indicated that some of the compounds exhibited potent fungicidal activity against Botrytis cinerea in vitro. Among these stilbene hybrids, compounds 11 showed promising inhibitory activity with the EC50 value of 144.6 μg/mL, which was superior to that of resveratrol (315.6 μg/mL). Remarkably, the considerably abnormal mycelial morphology was observed in the presence of compound 11. The inhibitory profile was further proposed by homology modeling and molecular docking studies, which showed the possible interaction of resveratrol and oxadiazole-stilbene hybrids with the cytochrome P450-dependent sterol 14α-demethylase from B. cinerea (BcCYP51) for the first time. Taken together, these results would provide new insights into the fungicidal mechanism of stilbenes, as well as an important clue for biology-oriented synthesis of stilbene hybrids with improved bioactivity against plant pathogenic fungi in crop protection.
Diabetic Risk Factors Promote Islet Amyloid Polypeptide Misfolding by a Common, Membrane-mediated Mechanism
Authors: Okada Alan K. , Teranishi Kazuki , Isas J. Mario , Bedrood Sahar , Chow Robert H. , Langen Ralf 
Published: August 2016

AbstractThe current diabetes epidemic is associated with a diverse set of risk factors including obesity and exposure to plastics. Notably, significant elevations of negatively charged amphiphilic molecules are observed in obesity (e.g. free fatty acids and phosphatidic acid) and plastics exposure (monophthalate esters). It remains unclear whether these factors share pathogenic mechanisms and whether links exist with islet amyloid polypeptide (IAPP) misfolding, a process central to β-cell dysfunction and death. Using a combination of fluorescence, circular dichroism and electron microscopy, we show that phosphatidic acid, oleic acid and the phthalate metabolite MBzP partition into neutral membranes and enhance IAPP misfolding. The elevation of negative charge density caused by the presence of the risk factor molecules stabilizes a common membrane-bound α-helical intermediate that, in turn, facilitates IAPP misfolding. This shared mechanism points to a critical role for the membrane-bound intermediate in disease pathogenesis, making it a potential target for therapeutic intervention.
REST is a hypoxia-responsive transcriptional repressor
Authors: Cavadas Miguel A. S. , Mesnieres Marion , Crifo Bianca , Manresa Mario C. , Selfridge Andrew C. , Keogh Ciara E. , Fabian Zsolt , Scholz Carsten C. , Nolan Karen A. , Rocha Liliane M. A. , Tambuwala Murtaza M. , Brown Stuart , Wdowicz Anita , Corbett Danielle , Murphy Keith J. , Godson Catherine , Cummins Eoin P. , Taylor Cormac T. , Cheong Alex 
Published: August 2016

AbstractCellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.
Anti-RAINBOW dye-specific antibodies as universal tools for the visualization of prestained protein molecular weight markers in Western blot analysis
Authors: Schüchner Stefan , Andorfer Peter , Mudrak Ingrid , Ogris Egon 
Published: August 2016

AbstractWestern blotting is one of the most widely used techniques in molecular biology and biochemistry. Prestained proteins are used as molecular weight standards in protein electrophoresis. In the chemiluminescent Western blot analysis, however, these colored protein markers are invisible leaving researchers with the unsatisfying situation that the signal for the protein of interest and the signal for the markers are not captured simultaneously and have to be merged in an error-prone step. To allow the simultaneous detection of marker proteins we generated monoclonal antibodies specific for the protein dyes. To elicit a dye rather than protein specific immune response we immunized mice sequentially with dye-carrier protein complexes, in which a new carrier protein was used for each subsequent immunization. Moreover, by sequentially immunizing with dye-carrier protein complexes, in which different but structurally related dyes were used, we could also generate an antibody, termed anti-RAINBOW, that cross-reacted even with structurally related dyes not used in the immunizations. Our novel antibodies represent convenient tools for the simultaneous Western blot detection of commercially available prestained marker proteins in combination with the detection of any specific protein of interest. These antibodies will render obsolete the anachronistic tradition of manually charting marker bands on film.
Understanding the structural basis of substrate recognition by Plasmodium falciparum plasmepsin V to aid in the design of potent inhibitors
Authors: Bedi Rajiv K. , Patel Chandan , Mishra Vandana , Xiao Huogen , Yada Rickey Y. , Bhaumik Prasenjit 
Published: August 2016

AbstractPlasmodium falciparumplasmepsin V (PfPMV) is an essential aspartic protease required for parasite survival, thus, considered as a potential drug target. This study reports the first detailed structural analysis and molecular dynamics simulation of PfPMV as an apoenzyme and its complexes with the substrate PEXEL as well as with the inhibitor saquinavir. The presence of pro-peptide in PfPMV may not structurally hinder the formation of a functionally competent catalytic active site. The structure of PfPMV-PEXEL complex shows that the unique positions of Glu179 and Gln222 are responsible for providing the specificity of PEXEL substrate with arginine at P3 position. The structural analysis also reveals that the S4 binding pocket in PfPMV is occupied by Ile94, Ala98, Phe370 and Tyr472 and therefore, does not allow binding of pepstatin, a potent inhibitor of most pepsin-like aspartic proteases. Among the screened inhibitors, the HIV-1 protease inhibitors and KNI compounds have higher binding affinities for PfPMV with saquinavir having the highest value. The presence of a flexible group at P2 and a bulky hydrophobic group at P3 position of the inhibitor is preferred in the PfPMV substrate binding pocket. Results from the present study will aid in the design of potent inhibitors of PMV.
Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy
Authors: Su Po-Jung , Wu Min-Hsien , Wang Hung-Ming , Lee Chia-Lin , Huang Wen-Kuan , Wu Chiao-En , Chang Hsien-Kun , Chao Yin-Kai , Tseng Chen-Kan , Chiu Tzu-Keng , Lin Nina Ming-Jung , Ye Siou-Ru , Lee Jane Ying-Chieh , Hsieh Chia-Hsun 
Published: August 2016

AbstractThe role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted.
Comparative Analysis of piggyBac, CRISPR/Cas9 and TALEN Mediated BAC Transgenesis in the Zygote for the Generation of Humanized SIRPA Rats
Authors: Jung Chris J. , Ménoret Séverine , Brusselle Lucas , Tesson Laurent , Usal Claire , Chenouard Vanessa , Remy Séverine , Ouisse Laure-Hélène , Poirier Nicolas , Vanhove Bernard , de Jong Pieter J. , Anegon Ignacio 
Published: August 2016

AbstractBAC transgenic mammalian systems offer an important platform for recapitulating human gene expression and disease modeling. While the larger body mass, and greater genetic and physiologic similarity to humans render rats well suited for reproducing human immune diseases and evaluating therapeutic strategies, difficulties of generating BAC transgenic rats have hindered progress. Thus, an efficient method for BAC transgenesis in rats would be valuable. Immunodeficient mice carrying a human SIRPA transgene have previously been shown to support improved human cell hematopoiesis. Here, we have generated for the first time, human SIRPA BAC transgenic rats, for which the gene is faithfully expressed, functionally active, and germline transmissible. To do this, human SIRPA BAC was modified with elements to work in coordination with genome engineering technologies-piggyBac, CRISPR/Cas9 or TALEN. Our findings show that piggyBac transposition is a more efficient approach than the classical BAC transgenesis, resulting in complete BAC integration with predictable end sequences, thereby permitting precise assessment of the integration site. Neither CRISPR/Cas9 nor TALEN increased BAC transgenesis. Therefore, an efficient generation of human SIRPA transgenic rats using piggyBac opens opportunities for expansion of humanized transgenic rat models in the future to advance biomedical research and therapeutic applications.
Functional characterization of a monoclonal antibody epitope using a lambda phage display-deep sequencing platform
Authors: Domina Maria , Lanza Cariccio Veronica , Benfatto Salvatore , Venza Mario , Venza Isabella , Borgogni Erica , Castellino Flora , Midiri Angelina , Galbo Roberta , Romeo Letizia , Biondo Carmelo , Masignani Vega , Teti Giuseppe , Felici Franco , Beninati Concetta 
Published: August 2016

AbstractWe have recently described a method, named PROFILER, for the identification of antigenic regions preferentially targeted by polyclonal antibody responses after vaccination. To test the ability of the technique to provide insights into the functional properties of monoclonal antibody (mAb) epitopes, we used here a well-characterized epitope of meningococcal factor H binding protein (fHbp), which is recognized by mAb 12C1. An fHbp library, engineered on a lambda phage vector enabling surface expression of polypeptides of widely different length, was subjected to massive parallel sequencing of the phage inserts after affinity selection with the 12C1 mAb. We detected dozens of unique antibody-selected sequences, the most enriched of which (designated as FrC) could largely recapitulate the ability of fHbp to bind mAb 12C1. Computational analysis of the cumulative enrichment of single amino acids in the antibody-selected fragments identified two overrepresented stretches of residues (H248-K254 and S140-G154), whose presence was subsequently found to be required for binding of FrC to mAb 12C1. Collectively, these results suggest that the PROFILER technology can rapidly and reliably identify, in the context of complex conformational epitopes, discrete “hot spots” with a crucial role in antigen-antibody interactions, thereby providing useful clues for the functional characterization of the epitope.