bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential molecular consequences of transgene integration: The R6/2 mouse example
Authors: Jacobsen Jessie C. , Erdin Serkan , Chiang Colby , Hanscom Carrie , Handley Renee R. , Barker Douglas D. , Stortchevoi Alex , Blumenthal Ian , Reid Suzanne J. , Snell Russell G. , MacDonald Marcy E. , Morton A. Jennifer , Ernst Carl , Gusella James F. , Talkowski Michael E. 
Published: January 2017

AbstractIntegration of exogenous DNA into a host genome represents an important route to generate animal and cellular models for exploration into human disease and therapeutic development. In most models, little is known concerning structural integrity of the transgene, precise site of integration, or its impact on the host genome. We previously used whole-genome and targeted sequencing approaches to reconstruct transgene structure and integration sites in models of Huntington’s disease, revealing complex structural rearrangements that can result from transgenesis. Here, we demonstrate in the R6/2 mouse, a widely used Huntington’s disease model, that integration of a rearranged transgene with coincident deletion of 5,444 bp of host genome within the gene Gm12695 has striking molecular consequences. Gm12695, the function of which is unknown, is normally expressed at negligible levels in mouse brain, but transgene integration has resulted in cortical expression of a partial fragment (exons 8–11) 3’ to the transgene integration site in R6/2. This transcript shows significant expression among the extensive network of differentially expressed genes associated with this model, including synaptic transmission, cell signalling and transcription. These data illustrate the value of sequence-level resolution of transgene insertions and transcription analysis to inform phenotypic characterization of transgenic models utilized in therapeutic research.
A 10-year observation of PM2.5-bound nickel in Xi’an, China: Effects of source control on its trend and associated health risks
Authors: Xu Hongmei , Ho Steven Sai Hang , Cao Junji , Guinot Benjamin , Kan Haidong , Shen Zhenxing , Ho Kin Fai , Liu Suixin , Zhao Zhuzi , Li Jianjun , Zhang Ningning , Zhu Chongshu , Zhang Qian , Huang Rujin 
Published: January 2017

AbstractThis study presents the first long term (10-year period, 2004–2013) datasets of PM2.5-bound nickel (Ni) concentration obtained from the daily sample in urban of Xi’an, Northwestern China. The Ni concentration trend, pollution sources, and the potential health risks associated to Ni were investigated. The Ni concentrations increased from 2004 to 2008, but then decreased due to coal consumption reduction, energy structure reconstruction, tighter emission rules and the improvement of the industrial and motor vehicle waste control techniques. With the comparison of distributions between workday and non-workday periods, the effectiveness of local and regional air pollution control policies and contributions of hypothetical Ni sources (industrial and automobile exhausts) were evaluated, demonstrating the health benefits to the populations during the ten years. Mean Ni cancer risk was higher than the threshold value of 10−6, suggesting that carcinogenic Ni still was a concern to the residents. Our findings conclude that there are still needs to establish more strict strategies and guidelines for atmospheric Ni in our living area, assisting to balance the relationship between economic growth and environmental conservation in China.
Identification of Key Residues for Urate Specific Transport in Human Glucose Transporter 9 (hSLC2A9)
Authors: Long Wentong , Panigrahi Rashmi , Panwar Pankaj , Wong Kenneth , O′Neill Debbie , Chen Xing-Zhen , Lemieux M. Joanne , Cheeseman Chris I. 
Published: January 2017

AbstractHuman glucose transporter 9 (hSLC2A9) is critical in human urate homeostasis, for which very small deviations can lead to chronic or acute metabolic disorders. Human SLC2A9 is unique in that it transports hexoses as well as the organic anion, urate. This ability is in contrast to other homologous sugar transporters such as glucose transporters 1 and 5 (SLC2A1 & SLC2A5) and the xylose transporter (XylE), despite the fact that these transporters have similar protein structures. Ourin silicosubstrate docking study has revealed that urate and fructose bind within the same binding pocket in hSLC2A9, yet with distinct orientations, and allowed us to identify novel residues for urate binding. Our functional studies confirmed that N429 is a key residue for both urate binding and transport. We have shown that cysteine residues, C181, C301 and C459 in hSLC2A9 are also essential elements for mediating urate transport. Additional data from chimæric protein analysis illustrated that transmembrane helix 7 of hSLC2A9 is necessary for urate transport but not sufficient to allow urate transport to be induced in glucose transporter 5 (hSLC2A5). These data indicate that urate transport in hSLC2A9 involves several structural elements rather than just a unique substrate binding pocket.
The aliphatic amidase AmiE is involved in regulation of Pseudomonas aeruginosa virulence
Authors: Clamens Thomas , Rosay Thibaut , Crépin Alexandre , Grandjean Teddy , Kentache Takfarinas , Hardouin Julie , Bortolotti Perrine , Neidig Anke , Mooij Marlies , Hillion Mélanie , Vieillard Julien , Cosette Pascal , Overhage Joerg , O’Gara Fergal , Bouffartigues Emeline , Dufour Alain , Chevalier Sylvie , Guery Benoit , Cornelis Pierre , Feuilloley Marc G. J. , Lesouhaitier Olivier 
Published: January 2017

AbstractWe have previously shown that the eukaryotic C-type natriuretic peptide hormone (CNP) regulates Pseudomonas aeruginosa virulence and biofilm formation after binding on the AmiC sensor, triggering the amiE transcription. Herein, the involvement of the aliphatic amidase AmiE in P. aeruginosa virulence regulation has been investigated. The proteome analysis of an AmiE over-producing strain (AmiE+) revealed an expression change for 138 proteins, including some that are involved in motility, synthesis of quorum sensing compounds and virulence regulation. We observed that the AmiE+ strain produced less biofilm compared to the wild type, and over-produced rhamnolipids. In the same line, AmiE is involved in P. aeruginosa motilities (swarming and twitching) and production of the quorum sensing molecules N-acyl homoserine lactones and Pseudomonas Quinolone Signal (PQS). We observed that AmiE overproduction reduced levels of HCN and pyocyanin causing a decreased virulence in different hosts (i.e. Dictyostelium discoideum and Caenorhabditis elegans). This phenotype was further confirmed in a mouse model of acute lung infection, in which AmiE overproduction resulted in an almost fully virulence decrease. Taken together, our data suggest that, in addition to its role in bacterial secondary metabolism, AmiE is involved in P. aeruginosa virulence regulation by modulating pilus synthesis and cell-to-cell communication.
SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma
Authors: Luo Yanzhang , Mok Tin Seak , Lin Xiuxian , Zhang Wanling , Cui Yizhi , Guo Jiahui , Chen Xing , Zhang Tao , Wang Tong 
Published: January 2017

AbstractNasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC.
Catalytic behavior of metal catalysts in high-temperature RWGS reaction: In-situ FT-IR experiments and first-principles calculations
Authors: Choi Sungjun , Sang Byoung-In , Hong Jongsup , Yoon Kyung Joong , Son Ji-Won , Lee Jong-Ho , Kim Byung-Kook , Kim Hyoungchul 
Published: January 2017

AbstractHigh-temperature chemical reactions are ubiquitous in (electro) chemical applications designed to meet the growing demands of environmental and energy protection. However, the fundamental understanding and optimization of such reactions are great challenges because they are hampered by the spontaneous, dynamic, and high-temperature conditions. Here, we investigated the roles of metal catalysts (Pd, Ni, Cu, and Ag) in the high-temperature reverse water-gas shift (RWGS) reaction using in-situ surface analyses and density functional theory (DFT) calculations. Catalysts were prepared by the deposition-precipitation method with urea hydrolysis and freeze-drying. Most metals show a maximum catalytic activity during the RWGS reaction (reaching the thermodynamic conversion limit) with formate groups as an intermediate adsorbed species, while Ag metal has limited activity with the carbonate species on its surface. According to DFT calculations, such carbonate groups result from the suppressed dissociation and adsorption of hydrogen on the Ag surface, which is in good agreement with the experimental RWGS results.
Alignment Solution for CT Image Reconstruction using Fixed Point and Virtual Rotation Axis
Authors: Jun Kyungtaek , Yoon Seokhwan 
Published: January 2017

AbstractSince X-ray tomography is now widely adopted in many different areas, it becomes more crucial to find a robust routine of handling tomographic data to get better quality of reconstructions. Though there are several existing techniques, it seems helpful to have a more automated method to remove the possible errors that hinder clearer image reconstruction. Here, we proposed an alternative method and new algorithm using the sinogram and the fixed point. An advanced physical concept of Center of Attenuation (CA) was also introduced to figure out how this fixed point is applied to the reconstruction of image having errors we categorized in this article. Our technique showed a promising performance in restoring images having translation and vertical tilt errors.
Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain
Authors: Torres-Pérez Jose Vicente , Sántha Péter , Varga Angelika , Szucs Peter , Sousa-Valente Joao , Gaal Botond , Sivadó Miklós , Andreou Anna P , Beattie Sara , Nagy Bence , Matesz Klara , C. Arthur J. Simon , Jancsó Gábor , Nagy Istvan 
Published: January 2017

AbstractTranscriptional changes in superficial spinal dorsal horn neurons (SSDHN) are essential in the development and maintenance of prolonged pain. Epigenetic mechanisms including post-translational modifications in histones are pivotal in regulating transcription. Here, we report that phosphorylation of serine 10 (S10) in histone 3 (H3) specifically occurs in a group of rat SSDHN following the activation of nociceptive primary sensory neurons by burn injury, capsaicin application or sustained electrical activation of nociceptive primary sensory nerve fibres. In contrast, brief thermal or mechanical nociceptive stimuli, which fail to induce tissue injury or inflammation, do not produce the same effect. Blocking N-methyl-D-aspartate receptors or activation of extracellular signal-regulated kinases 1 and 2, or blocking or deleting the mitogen- and stress-activated kinases 1 and 2 (MSK1/2), which phosphorylate S10 in H3, inhibit up-regulation in phosphorylated S10 in H3 (p-S10H3) as well as fos transcription, a down-stream effect of p-S10H3. Deleting MSK1/2 also inhibits the development of carrageenan-induced inflammatory heat hyperalgesia in mice. We propose that p-S10H3 is a novel marker for nociceptive processing in SSDHN with high relevance to transcriptional changes and the development of prolonged pain.
Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium
Authors: Fan Hanlu , Du Xiaohong , Zhang Jingyuan , Zheng Han , Lu Xiaohui , Wu Qihui , Li Haifeng , Wang Han , Shi Yi , Gao George , Zhou Zhuan , Tan Dun-Xian , Li Xiangdong 
Published: January 2017

AbstractThe Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs.
Safety and Efficacy of Single-Stage Surgical Treatment for Congenital Scoliosis Associated with Intraspinal Mass
Authors: Zhang Bo-bo , Tao Hui-ren , Wu Tai-lin , Wang Lin , Duan Chun-guang , Zhang Tao , Li Tao , Yang Wei-zhou , Liu Ming , Ma Jun 
Published: January 2017

AbstractFor congenital scoliosis associated with intraspinal anomaly, surgical treatment is often advocated. However, the safety and efficacy of single-stage intraspinal mass resection and scoliosis correction remain unclear. The purpose of this study was to retrospectively evaluate the feasibility and risk factors of single-stage surgical treatment for congenital scoliosis associated with intraspinal mass. Patients’ clinical records were reviewed for demographic and radiographic data, operating time, intraoperative blood loss, perioperative complications, and postoperative pathologic results. Two female and 5 male patients with an average age of 19.14 ± 7.52 years (range, 11–31 years) were evaluated. Patients were followed for a minimum of 24 months after initial surgical treatment, with an average of 49.71 ± 32.90 months (range, 27–99 months). Spinal curvature was corrected from an average of 69.57 ± 20.44° to 29.14 ± 9.87°, demonstrating a mean correction rate of 55.05% ± 18.75%. No obvious loss of correction was observed at the final follow-up. Complications included transient neurologic deficit, cerebrospinal fluid leakage, and intraspinal mass recurrence in 1 patient each. There was no paralysis or permanent nerve damage. In conclusion, simultaneous intraspinal mass resection and scoliosis correction appears to be safe and effective.
Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression
Authors: Bobko Andrey A. , Eubank Timothy D. , Driesschaert Benoit , Dhimitruka Ilirian , Evans Jason , Mohammad Rahman , Tchekneva Elena E. , Dikov Mikhail M. , Khramtsov Valery V. 
Published: January 2017

AbstractNoninvasivein vivoassessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique forin vivoconcurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi],pO2, pHeand tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression.
Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin
Authors: Marín-Menéndez Alejandro , Montis Costanza , Díaz-Calvo Teresa , Carta Davide , Hatzixanthis Kostas , Morris Christopher J. , McArthur Michael , Berti Debora 
Published: January 2017

AbstractAntimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.
Optimal Down Regulation of mRNA Translation
Authors: Zarai Yoram , Margaliot Michael , Tuller Tamir 
Published: January 2017

AbstractDown regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results.
Survival rate of eukaryotic cells following electrophoretic nanoinjection
Authors: Simonis Matthias , Hübner Wolfgang , Wilking Alice , Huser Thomas , Hennig Simon 
Published: January 2017

AbstractInsertion of foreign molecules such as functionalized fluorescent probes, antibodies, or plasmid DNA to living cells requires overcoming the plasma membrane barrier without harming the cell during the staining process. Many techniques such as electroporation, lipofection or microinjection have been developed to overcome the cellular plasma membrane, but they all result in reduced cell viability. A novel approach is the injection of cells with a nanopipette and using electrophoretic forces for the delivery of molecules. The tip size of these pipettes is approximately ten times smaller than typical microinjection pipettes and rather than pressure pulses as delivery method, moderate DC electric fields are used to drive charged molecules out of the tip. Here, we show that this approach leads to a significantly higher survival rate of nanoinjected cells and that injection with nanopipettes has a significantly lower impact on the proliferation behavior of injected cells. Thus, we propose that injection with nanopipettes using electrophoretic delivery is an excellent alternative when working with valuable and rare living cells, such as primary cells or stem cells.
ApoA-IV improves insulin sensitivity and glucose uptake in mouse adipocytes via PI3K-Akt Signaling
Authors: Li Xiaoming , Wang Fei , Xu Min , Howles Philip , Tso Patrick 
Published: January 2017

AbstractInsulin resistance is a risk factor for type 2 diabetes mellitus. We investigated the effect of ApoA-IV on glucose uptake in the adipose and muscle tissues of mice and cultured 3T3-L1 adipocytes. We found that treatment with ApoA-IV lowered fasting blood glucose in both WT and diabetic KKAy mice by increasing glucose uptake in cardiac muscle, white adipose tissue, and brown adipose tissue through a mechanism that was partially insulin independent. Cell culture experiments showed that ApoA-IV improved glucose uptake in adipocytes in the absence of insulin by upregulating GLUT4 translocation by PI3K mediated activation of Akt signaling pathways. Considering our previous finding that ApoA-IV treatment enhanced pancreatic insulin secretion, these results suggests that ApoA-IV acts directly upon adipose tissue to improve glucose uptake and indirectly via insulin signaling. Our findings warrant future studies to identify the receptor for ApoA-IV and the downstream targets of PI3K-Akt signaling that regulate glucose uptake in adipocytes as potential therapeutic targets for treating insulin resistance.