bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification and localization of oncogenic receptor tyrosine kinase variant transcripts using molecular inversion probes
Authors: van den Heuvel Corina N. A. M. , Das Arvid I. , de Bitter Tessa , Simmer Femke , Wurdinger Thomas , Molina-Vila Miguel Angel , Leenders William P. J. 
Published: April 2018

AbstractOncogenic membrane receptor tyrosine kinases such as MET and EGFR, or auto-active variants thereof, are important targets for cancer precision therapy. Targeted inhibition of these oncogenic receptors however invariably leads to resistance, resulting from acquisition of resistance-inducing mutations or from selective outgrowth of a priori resistant tumour cells. Most applied molecular protocols cannot distinguish between intracellular and intercellular heterogeneity of oncogene (variant) expression, which may lead to misinterpretation of the molecular make-up of a cancer and suboptimal application of targeted therapies. We here combined two related techniques to allow semiquantitative and localized in situ detection of specific transcript splice variants using single molecule molecular inversion probe (smMIP)-based next generation sequencing and padlock probe-based rolling circle amplification, respectively. We show highly specific padlock probe-based multiplex detection of MET, METΔ7-8 and METΔ14 transcripts, lacking exons 7–8 and exon 14 respectively, and of EGFR and the auto-active EGFRvIII, lacking exons 2–7. The combination of quantitative transcript variant detection with smMIPs and transcript localization using padlock probes can be used for detection of oncogenic transcripts on the single-cell level, allowing study of tumour heterogeneity. Visualization of tumour heterogeneity can shed light on the biology underlying drug resistance and potentially improve targeted therapeutics.
Near-Infrared Fluorescence Imaging Directly Visualizes Lymphatic Drainage Pathways and Connections between Superficial and Deep Lymphatic Systems in the Mouse Hindlimb
Authors: Nakajima Yukari , Asano Kimi , Mukai Kanae , Urai Tamae , Okuwa Mayumi , Sugama Junko , Nakatani Toshio 
Published: April 2018

AbstractSince lymphedema rarely develops in the mouse hindlimb, the underlying mechanisms remain unclear. We herein investigated the resolution of chronic hindlimb lymphedema in mice using a Near-Infrared Fluorescence (NIRF) imaging system. Nineteen 7–28-week-old BALB/c male and female mice were injected with two dyes for lymphography and dissection. Lymphadenectomy was performed on six male mice to completely obstruct lymph flow in the hindlimb. Edematous changes in both hindlimbs were compared until 60 days after surgery. The NIRF imaging system detected three lymphatic collecting systems in the mouse hindlimb: superficial lateral, superficial medial, and deep medial. It also showed connections between the superficial and deep lymphatic systems in the inguinal region. Lymphadenectomy of the iliac, inguinal, and popliteal lymph nodes caused edematous changes. However, lymph flow in these operated areas restarted within 60 days and the severity of lymphedema appeared to be low. NIRF imaging showed that the deep medial system and a connection between the superficial and deep lymphatic systems in the inguinal region drain lymph from the hindlimb. This is the one reasons why lymphedema does not develop in the mouse hindlimb. The stable obstruction of lymph flow in these three systems is desired to develop chronic lymphedema.
Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
Authors: Mørkholt Anne Skøttrup , Kastaniegaard Kenneth , Trabjerg Michael Sloth , Gopalasingam Gopana , Niganze Wanda , Larsen Agnete , Stensballe Allan , Nielsen Søren , Nieland John Dirk 
Published: April 2018

AbstractMultiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self-proteins. The involvement of autoantibodies in MS pathogenesis has been suggested to initiate and drive progression of inflammation; however, the etiology of MS remains unknown. The effect of etomoxir and interferon-β (IFN-β) was examined in an experimental-autoimmune-encephalomyelitis (EAE) model of MS. Moreover, the impact of etomoxir and IFN-β on recognition of brain proteins in serum from EAE rats was examined with the purpose of identifying the autoantibody reactivities involved in MS. Animals treated with etomoxir on day 1 exhibited a statistically significantly lower disease score than animals treated with IFN-β (on day 1 or 5) or placebo. Etomoxir treatment on day 5 resulted in a significantly lower disease score than IFN-β treatment on day 1. After disease induction antibodies was induced to a broad pallet of antigens in the brain. Surprisingly, by blocking CPT1 and therewith lipid metabolism several alterations in the antibody response was observed suggesting that autoantibodies play a role in the EAE animal model.
Comparison of the safety and efficacy of triple sequential therapy and transscleral cyclophotocoagulation for neovascular glaucoma in the angle-closure stage
Authors: Hong Ying , Hu Yuntao , Dou Hongliang , Wang Changguan , Zhang Chun , Ma Zhizhong 
Published: April 2018

AbstractTo compare the efficacy and safety of triple therapy combining intravitreal injection of anti-vascular endothelial growth factor, trabeculectomy, and pan-retinal photocoagulation via binocular indirect ophthalmoscopy, with that of transscleral cyclophotocoagulation (TCP) to treat neovascular glaucoma in the angle-closure stage. Eighteen triple therapy patients and 25 TCP patients between May 2014 and May 2016 were retrospectively analysed. Anterior chamber puncture and anti-VEGF intravitreal injection were performed on the first day of sequential therapy. Trabeculectomy was performed 3–5 d after injection; pan-retinal laser photocoagulation via binocular indirect ophthalmoscopy was initiated 5–7 d later. The IOP of the triple therapy group was lower than that of the TCP group (15.2 ± 2.2 vs. 20.0 ± 8.5 mmHg) and fewer anti-glaucoma drugs were used (0.5 ± 1.0 vs. 0.6 ± 1.0) after treatment. The success rates of the two groups were 89% and 60% respectively (P = 0.032). The visual function of 94% of triple therapy patients was preserved or improved compared to 64% of TCP patients with statistical significance (P = 0.028). No patient in the triple therapy group showed hypotony or eyeball atrophy. Compared to TCP, triple therapy shows higher success rate, fewer complications, and attributes to visual function preservation.
The orphan germinant receptor protein GerXAO (but not GerX3b) is essential for L-alanine induced germination in Clostridium botulinum Group II
Authors: Brunt Jason , Carter Andrew T. , Pye Hannah V. , Peck Michael W. 
Published: April 2018

AbstractClostridium botulinum is an anaerobic spore forming bacterium that produces the potent botulinum neurotoxin that causes a severe and fatal neuro-paralytic disease of humans and animals (botulism). C. botulinum Group II is a psychrotrophic saccharolytic bacterium that forms spores of moderate heat resistance and is a particular hazard in minimally heated chilled foods. Spore germination is a fundamental process that allows the spore to transition to a vegetative cell and typically involves a germinant receptor (GR) that responds to environmental signals. Analysis of C. botulinum Group II genomes shows they contain a single GR cluster (gerX3b), and an additional single gerA subunit (gerXAO). Spores of C. botulinum Group II strain Eklund 17B germinated in response to the addition of L-alanine, but did not germinate following the addition of exogenous Ca2+-DPA. Insertional inactivation experiments in this strain unexpectedly revealed that the orphan GR GerXAO is essential for L-alanine stimulated germination. GerX3bA and GerX3bC affected the germination rate but were unable to induce germination in the absence of GerXAO. No role could be identified for GerX3bB. This is the first study to identify the functional germination receptor of C. botulinum Group II.
Time-lapse 3D imaging by positron emission tomography of Cu mobilized in a soil column by the herbicide MCPA
Authors: Kulenkampff Johannes , Stoll Madeleine , Gründig Marion , Mansel Alexander , Lippmann-Pipke Johanna , Kersten Michael 
Published: April 2018

AbstractPhenoxyalkanoic acids like the 4-chloro-2-methylphenoxyacetic acid (MCPA) are the second highest used xenobiotic herbicides worldwide after glyphosate because of their apparently favorable environmental properties. Experimental batch equilibration data suggested a reduced Cu adsorption efficiency with the soil mineral goethite below pH 6 in presence of MCPA. This has been verified by advanced surface complexation adsorption modelling involving dissolved Cu-MCPA complexation constants. Positron emission tomography is a non-invasive molecular imaging method for time-resolved three-dimensional information commonly applied on non-retarded tracers in soil core scale experiments. Mineral surface reactive tracers like Cu-64 are too immobile for the relatively short observation times available with this advanced imaging technique. However, Cu-64 radiolabeled Cu-MCPA complex migration could be observed in as long as 10-cm artificial soil test columns where break-through occurred within a few days. For the first time, time-lapse movies of Cu migration in the opaque soil columns were recorded using this novel reactive transport process tomography approach.
Chemical shift extremum of 129Xe(aq) reveals details of hydrophobic solvation
Authors: Peuravaara Petri , Karjalainen Jouni , Zhu Jianfeng , Mareš Jiří , Lantto Perttu , Vaara Juha 
Published: April 2018

AbstractThe 129Xe chemical shift in an aqueous solution exhibits a non-monotonic temperature dependence, featuring a maximum at 311 K. This is in contrast to most liquids, where the monotonic decrease of the shift follows that of liquid density. In particular, the shift maximum in water occurs at a higher temperature than that of the maximum density. We replicate this behaviour qualitatively via a molecular dynamics simulation and computing the 129Xe chemical shift for snapshots of the simulation trajectory. We also construct a semianalytical model, in which the Xe atom occupies a cavity constituted by a spherical water shell, consisting of an even distribution of solvent molecules. The temperature dependence of the shift is seen to result from a product of the decreasing local water density and an increasing term corresponding to the energetics of the Xe-H2O collisions. The latter moves the chemical shift maximum up in temperature, as compared to the density maximum. In water, the computed temperature of the shift maximum is found to be sensitive to both the details of the binary chemical shift function and the coordination number. This work suggests that, material parameters allowing, the maximum should be exhibited by other liquids, too.
LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
Authors: Arunkumar Ganesan , Anand Shankar , Raksha Partha , Dhamodharan Shankar , Prasanna Srinivasa Rao Harikrishnan , Subbiah Shanmugam , Murugan Avaniyapuram Kannan , Munirajan Arasambattu Kannan 
Published: April 2018

AbstractLong non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3′-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome.
QM/MM free energy Simulations of an efficient Gluten Hydrolase (Kuma030) Implicate for a Reactant-State Based Protein-Design Strategy for General Acid/Base Catalysis
Authors: Wang Xia , Li Ruirui , Cui Wenchao , Li Qiang , Yao Jianzhuang 
Published: April 2018

AbstractIt is a grand attraction for contemporary biochemists to computationally design enzymes for novel chemical transformation or improved catalytic efficiency. Rosetta by Bakeret al. is no doubt the leading software in the protein design society. Generally, optimization of the transition state (TS) is part of the Rosetta’s protocol to enhance the catalytic efficiency of target enzymes, since TS stabilization is the determining factor for catalytic efficiency based on the TS theory (TST). However, it is confusing that optimization of the reactant state (RS) also results in significant improvement of catalytic efficiency in some cases, such as design of gluten hydrolase (Kuma030). Therefore, it is interesting to uncover underlying reason why a better binding in the RS leading to an increasedkcat. In this study, the combined quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy (PMF) simulations, pKacalculation, and the statistical analysis such as the ANOVA test were carried out to shed light on the interesting but elusive question. By integration of our computational results and general acid/base theory, we answered the question why optimization of RS stabilization leads to a better TS stabilization in the general acid/base catalysis. In addition, a new and simplified protein-design strategy is proposed for the general acid/base catalysis. The idea, that application of traditional well-defined enzyme mechanism to protein design strategy, would be a great help for methodology development of protein design.
Association between amniotic fluid evaluation and fetal biometry: a prospective French “Flash” study
Authors: Fuchs Florent , Aouinti Safa , Souaied Manel , Keller Valentin , Picot Marie-Christine , Fries Nicolas , Ayoubi Jean-Marc , Picone Olivier 
Published: April 2018

AbstractWe aimed to study the association between three different methods of assessing the amount of amniotic fluid (subjective method (SM), deepest vertical pocket (DVP) and amniotic fluid index (AFI)) and estimated fetal weight (EFW) (in percentile or Z-score) after adjustment on maternal-fetal parameters. We performed a nationwide cross-sectional study through the French network of obstetric sonographers using the “flash” study method and including low-risk singleton pregnancies from 18–40 weeks. Crude and adjusted odds ratio were computed after stratification upon 2nd and 3rd trimester of pregnancy. 1667 ultrasound scans performed by 65 operators were included. Only Z-score of EFW was significantly associated with SM in both trimesters. For DVP and AFI, Z-score of EFW and male fetal gender was significantly associated with them in 2nd trimester. In the 3rd trimester, both Z-score of EFW and large (LGA) or small for gestational age (SGA) fetus were significantly associated with AFI. and DVP. Overweight woman and class I obesity women were also significantly associated with DVP modification. In conclusion, all three methods of amniotic fluid evaluation are significantly associated to estimated fetal weight. DVP and AFI appeared equivalent except that maternal-fetal factors seemed to have a higher impact in DVP than AFI.
Magnetic Induction Spectroscopy for Permeability Imaging
Authors: Ma Lu , Soleimani Manuchehr 
Published: April 2018

AbstractThe structural health monitoring of ferromagnetic materials is essential for controlling product quality. This paper presents the first known characterisation, utilising magnetic induction spectroscopy, of the magnetic permeability of ferromagnetic materials, a property that can facilitate such monitoring. Magnetic induction coils are interrogated by a sweep of excitation frequencies in the range of 1–100 kHz, with amplitudes of induced voltages collected from both non-magnetic and ferromagnetic specimens, and their associated spectral permeability imaged. The reconstructed images show that magnetic permeability can be reconstructed using frequency difference imaging in the investigated frequency range. As such, the relative magnetic permeability of a ferromagnetic specimen can be reconstructed without needing a time difference measurement. This provides a robust imaging approach for the material characterisation of ferromagnetic specimens.
Understanding the ontogeny and succession of Bacillus velezensis and B. subtilis subsp. subtilis by focusing on kimchi fermentation
Authors: Cho Min Seok , Jin Yong Ju , Kang Bo Kyoung , Park Yu Kyoung , Kim ChangKug , Park Dong Suk 
Published: April 2018

AbstractBacillus subtilis and B. velezensis are frequently isolated from various niches, including fermented foods, water, and soil. Within the Bacillus subtilis group, B. velezensis and B. subtilis subsp. subtilis have received significant attention as biological resources for biotechnology-associated industries. Nevertheless, radical solutions are urgently needed to identify microbes during their ecological succession to accurately confirm their action at the species or subspecies level in diverse environments, such as fermented materials. Thus, in this study, previously published genome data of the B. subtilis group were compared to exploit species- or subspecies-specific genes for use as improved qPCR targets to detect B. velezensis and B. subtilis subsp. subtilis in kimchi samples. In silico analyses of the selected genes and designed primer sequences, in conjunction with SYBR Green real-time PCR, confirmed the robustness of this newly developed assay. Consequently, this study will allow for new insights into the ontogeny and succession of B. velezensis and B. subtilis subsp. subtilis in various niches. Interestingly, in white kimchi without red pepper powder, neither B. subtilis subsp. subtilis nor B. velezensis was detected.
In vitro acellular dissolution of mineral fibres: A comparative study
Authors: Gualtieri Alessandro F. , Pollastri Simone , Bursi Gandolfi Nicola , Gualtieri Magdalena Lassinantti 
Published: April 2018

AbstractThe study of the mechanisms by which mineral fibres promote adverse effects in both animals and humans is a hot topic of multidisciplinary research with many aspects that still need to be elucidated. Besides length and diameter, a key parameter that determines the toxicity/pathogenicity of a fibre is biopersistence, one component of which is biodurability. In this paper, biodurability of mineral fibres of social and economic importance (chrysotile, amphibole asbestos and fibrous erionite) has been determined for the first time in a systematic comparative way from in vitro acellular dissolution experiments. Dissolution was possible using the Gamble solution as simulated lung fluid (pH = 4 and at body temperature) so to reproduce the macrophage phagolysosome environment. The investigated mineral fibres display very different dissolution rates. For a 0.25 μm thick fibre, the calculated dissolution time of chrysotile is in the range 94–177 days, very short if compared to that of amphibole fibres (49–245 years), and fibrous erionite (181 years). Diffraction and SEM data on the dissolution products evidence that chrysotile rapidly undergoes amorphization with the formation of a nanophasic silica-rich fibrous metastable pseudomorph as first dissolution step whereas amphibole asbestos and fibrous erionite show minor signs of dissolution even after 9–12 months.
The positive effect of chick embryo and nutrient mixture on bone marrow- derived mesenchymal stem cells from aging rats
Authors: Ma Jia , Guo Yanru , Hu Jialei , Pan Yue , Qi Xia , Wang Huaxin , Jia Li 
Published: April 2018

AbstractThe aging of many mammalian tissues is associated with loss of functional adult stem cells, especially bone marrow-derived mesenchymal stem cells (BMSCs). This study was aimed to analyze the biological effect of chick embryo (CE) and nutrient mixture (NM) on the BMSCs of aging rats. The aging rat model was established to be induced by D-galactose (500 mg/kg/d) for 90 days. Meanwhile, aging rats were fed with CE and NM in different dose manner by intragastric administration. At the end of the experimental period, serum was collected from rats and used for BMSCs culture. Flow cytometric analysis was used to investigate the BMSCs surface markers. Alizarin Red and oil red O staining were performed to evaluate the multi-lineage differentiation of BMSCs. The results showed that CE plus NM increased the telomere length of BMSCs and promoted BMSCs proliferation. Moreover, CE plus NM administration promoted BMSCs differentiation into osteoblasts and suppressed differentiation into adipocytes. High-throughput sequencing analysis revealed that there were 326 genes were up-regulated and 59 genes were down-regulated in BMSCs of aging rats treated with CE plus NM. In conclusion, CE plus NM supplement had potential to delay aging through the recovery of BMSCs senescence and could be used as a safe effective approach for nutritional therapy of anti-aging.
Discovery of a jet-like structure with overionized plasma in the SNR IC 443
Authors: Greco Emanuele , Miceli Marco , Orlando Salvatore , Peres Giovanni , Troja Eleonora , Bocchino Fabrizio 
Published: April 2018

Context. IC 443 is a supernova remnant (SNR) located in a quite complex environment since it interacts with nearby clouds. Indications for the presence of overionized plasma have been found though the possible physical causes of overionization are still debated. Moreover, because of its peculiar position and proper motion, it is not clear if the pulsar wind nebula (PWN) within the remnant is the relic of the IC 443 progenitor star or just a rambling one seen in projection on the remnant.
Aims. Here we address the study of IC 443 plasma in order to clarify the relationship PWN-remnant, the presence of overionization and the origin of the latter.
Methods. We analyzed two XMM-Newton observations producing background-subtracted, vignetting-corrected and mosaicked images in two different energy bands and we performed a spatially resolved spectral analysis of the X-ray emission.
Results. We identified an elongated (jet-like) structure with Mg-rich plasma in overionization. The head of the jet is interacting with a molecular cloud and the jet is aligned with the position of the PWN at the instant of the supernova explosion. Interestingly, the direction of the jet of ejecta is somehow consistent with the direction of the PWN jet.
Conclusions. Our discovery of a jet of ejecta in IC 443 enlarge the sample of core-collapse SNRs with collimated ejecta structures. IC 443’s jet is the first one which shows overionized plasma, possibly associated with the adiabatic expansion of ejecta. The match between the jet’s direction and the original position of the PWN strongly supports the association between the neutron star and IC 443.