bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-class I PI3-kinase inhibitor BKM120 induces MEK1/2-dependent mitotic catastrophe in non-Hodgkin lymphoma leading to apoptosis or polyploidy determined by Bax/Bak and p53
Authors: Müller Anja , Gillissen Bernd , Richter Antje , Richter Anja , Chumduri Cindrilla , Daniel Peter T. , Scholz Christian W. 
Published: March 2018

AbstractConstitutive signaling of PI3K/Akt/mTOR plays a prominent role in malignant transformation and progression of B-cell non-Hodgkin lymphomas (B-NHL) underscoring the need for PI3K targeted therapies. The pan-class I PI3-kinase inhibitor BKM120 has shown preclinical activity in distinct malignancies and is currently tested in clinical trials. Intratumor heterogeneity is an intrinsic property of cancers that contributes to drug resistance and tumor recurrence. Here, we demonstrate that inhibition of PI3-kinases by BKM120 attenuates growth and survival of B-NHL cell lines by inducing mitotic arrest with subsequent induction of intrinsic apoptosis. BKM120-mediated downregulation of Cyclin A and activation of the CDK1/Cyclin B1 complex facilitates mitotic entry. In addition, concomitant BKM120-mediated upregulation of Cyclin B1 expression attenuates completion of mitosis, which results in mitotic catastrophe and apoptotic cell death. In Bax and Bak deficient B-NHL, which are resistant to BKM120-induced apoptosis, BKM120-induced mitotic catastrophe results in polyploidy. Upon re-expression of wt p53 in these p53 mutated cells, BKM120-induced polyploidy is strongly reduced demonstrating that the genetic status of the cells determines the outcome of a BKM120-mediated pathway inhibition. Mitotic catastrophe and unfavorable induction of polyploidy can be prevented in this setting by additional inhibition of MEK1/2 signaling. Combining MEK1/2 inhibitors with BKM120 enhances the anti-tumor effects of BKM120, prevents prognostic unfavorable polyploidy and might be a potential strategy for the treatment of B-NHL.
Biomedical findings from NASA’s Project Mercury: a case series
Authors: Carpentier William R. , Charles John B. , Shelhamer Mark , Hackler Amanda S. , Johnson Tracy L. , Domingo Catherine M. M. , Sutton Jeffrey P. , Scott Graham B. I. , Wotring Virginia E. 
Published: March 2018

AbstractThe United States first sent humans into space during six flights of Project Mercury from May 1961 to May 1963. These flights were brief, with durations ranging from about 15 min to just over 34 h. A primary purpose of the project was to determine if humans could perform meaningful tasks while in space. This was supported by a series of biomedical measurements on each astronaut before, during (when feasible), and after flight to document the effects of exposure to the spaceflight environment. While almost all of the data presented here have been published in technical reports, this is the first integrated summary of the main results. One unexpected finding emerges: the major physiological changes associated with these short-term spaceflights are correlated more strongly with time spent by the astronaut in a spacesuit than with time spent in space per se. Thus, exposure to the direct stressors of short-duration (up to 34 h) spaceflight was not the dominant factor influencing human health and performance. This is relevant to current spaceflight programs and especially to upcoming commercial flights in which time spent in space (as on a suborbital flight) will be minor compared to the time spent in associated preparation, ascent, and return.
Large-scale computational drug repositioning to find treatments for rare diseases
Authors: Govindaraj Rajiv Gandhi , Naderi Misagh , Singha Manali , Lemoine Jeffrey , Brylinski Michal 
Published: March 2018

AbstractRare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning. In order to find new targets for known drugs ultimately leading to drug repositioning, we recently developedeMatchSite, a new computer program to compare drug-binding sites. In this study,eMatchSite is combined with virtual screening to systematically explore opportunities to reposition known drugs to proteins associated with rare diseases. The effectiveness of this integrated approach is demonstrated for a kinase inhibitor, which is a confirmed candidate for repositioning to synapsin Ia. The resulting dataset comprises 31,142 putative drug-target complexes linked to 980 orphan diseases. The modeling accuracy is evaluated against the structural data recently released for tyrosine-protein kinase HCK. To illustrate how potential therapeutics for rare diseases can be identified, we discuss a possibility to repurpose a steroidal aromatase inhibitor to treat Niemann-Pick disease type C. Overall, the exhaustive exploration of the drug repositioning space exposes new opportunities to combat orphan diseases with existing drugs. DrugBank/Orphanet repositioning data are freely available to research community athttps://osf.io/qdjup/.
Thermally Tunable Ultra-wideband Metamaterial Absorbers based on Three-dimensional Water-substrate construction
Authors: Shen Yang , Zhang Jieqiu , Pang Yongqiang , Zheng Lin , Wang Jiafu , Ma Hua , Qu Shaobo 
Published: March 2018

AbstractDistilled water has frequency dispersive characteristic and high value of imaginary part in permittivity, which can be seen as a good candidate of broadband metamaterial absorbers(MAs) in microwave. Here, an interesting idea based on the combination of water-substrate and metallic metamaterial in the three-dimensional construction is proposed, which can achieve outstanding broadband absorption. As a proof, the distilled water is filled into the dielectric reservoir as ultra-thin water-substrate, and then the water-substrates are arranged on the metal backplane periodically as three-dimensional water-substrate array(TWA). Simulation shows that the TWA achieves broadband absorption with the efficiency more than 90% from 8.3 to 21.0 GHz. Then, the trigonal metallic fishbone structure is introduced here between the water-substrate and the dielectric reservoir periodically as three-dimensional water-substrate metamaterial absorber(TWMA). The proposed TWMA could achieve ultra-broadband absorption from 2.6 to 16.8 GHz, which has increase by 64.8% in relative absorption bandwidth. Meanwhile, due to the participation of distilled water, the thermally tunable property also deserves to be discussed here. In view of the outstanding performance, it is worth to expect a wide range of applications to emerge inspired from the proposed construction.
Freely suspended perforated polymer nanomembranes for protein separations
Authors: Schuster Christian , Rodler Agnes , Tscheliessnig Rupert , Jungbauer Alois 
Published: March 2018

AbstractSelective removal of nanometer-sized compounds such as proteins from fluids is an often challenging task in many scientific and industrial areas. Addressing such tasks with highly efficient and selective membranes is desirable since commonly used chromatographic approaches are expensive and difficult to scale up. Nanomembranes, molecularly thin separation layers, have been predicted and shown to possess outstanding properties but in spite ultra-fast diffusion times and high-resolution separation, to date they generally lack either of two crucial characteristics: compatibility with biological fluids and low-cost production. Here we report the fast and easy fabrication of highly crosslinked polymer membranes based on a thermoset resin (poly[(o-cresyl glycidyl ether)-co-formaldehyde (PCGF) cured with branched polyethyleneimine (PEI)) with nanoscale perforations of 25 nm diameter. During spin casting, microphase separation of a polylactide-co-glycolide induces the formation of nanometer sized domains that serve as templates for perforations which penetrate the 80 nm thick membranes. Ultrathin perforated nanomembranes can be freely suspended on the cm scale, exhibit high mechanical strength, low surface energies and a sharp permeability cutoff at a hydrodynamic diameter of 10 nm suitable for protein separations.
Prevalence of the single-nucleotide polymorphism rs11554137 (IDH1105GGT) in brain tumors of a cohort of Italian patients
Authors: Acquaviva Giorgia , Visani Michela , de Biase Dario , Marucci Gianluca , Franceschi Enrico , Tosoni Alicia , Brandes Alba A. , Rhoden Kerry J. , Pession Annalisa , Tallini Giovanni 
Published: March 2018

AbstractIDH mutational status is required for proper diagnosis according to the WHO criteria revised in 2016. The single nucleotide polymorphism (SNP) rs11554137 (IDH1105GGT) at codon 105 of IDH1 has been reported in patients with several tumor types, including those with glioma. The aim of this study is to investigate the prevalence of IDH1105GGT in a cohort of brain tumors, and its association with clinicopathologic features and IDH1 and IDH2 missense mutations. Exon 4 of IDH1 and IDH2 was analyzed in a series of brain tumors classified according to current WHO criteria. DNA from control individuals was analyzed to infer the prevalence of IDH1105GGT in the reference population. Analysis was performed using next generation sequencing. IDH1105GGT was three times more frequent in patients with tumors (44/293 cases, 15.0%) vs. population controls (6/109, 5.5%) (p = 0.0102). IDH1105GGT was more frequent in grade III tumors (26.1%) compared to grade II (10.9%, p = 0.038) and grade IV tumors (13.7%, p = 0.041). IDH1
105GGT
was more frequent in grade II and III tumors without an IDH tumor missense mutation (43.8%) than in those with (11.5%, p = 0.005). The IDH1105GGT SNP likely represents an important genetic marker, worthy of additional investigation to better understand the clinical and biological features of IDH-WT infiltrating gliomas.
Sharing of photobionts in sympatric populations of Thamnolia and Cetraria lichens: evidence from high-throughput sequencing
Authors: Onuț-Brännström Ioana , Benjamin Mitchell , Scofield Douglas G. , Heiðmarsson Starri , Andersson Martin G. I. , Lindström Eva S. , Johannesson Hanna 
Published: March 2018

AbstractIn this study, we explored the diversity of green algal symbionts (photobionts) in sympatric populations of the cosmopolitan lichen-forming fungi Thamnolia and Cetraria. We sequenced with both Sanger and Ion Torrent High-Throughput Sequencing technologies the photobiont ITS-region of 30 lichen thalli from two islands: Iceland and Öland. While Sanger recovered just one photobiont genotype from each thallus, the Ion Torrent data recovered 10–18 OTUs for each pool of 5 lichen thalli, suggesting that individual lichens can contain heterogeneous photobiont populations. Both methods showed evidence for photobiont sharing between Thamnolia and Cetraria on Iceland. In contrast, our data suggest that on Öland the two mycobionts associate with distinct photobiont communities, with few shared OTUs revealed by Ion Torrent sequencing. Furthermore, by comparing our sequences with public data, we identified closely related photobionts from geographically distant localities. Taken together, we suggest that the photobiont composition in Thamnolia and Cetraria results from both photobiont-mycobiont codispersal and local acquisition during mycobiont establishment and/or lichen growth. We hypothesize that this is a successful strategy for lichens to be flexible in the use of the most adapted photobiont for the environment.
Thermal conductivity reduction in silicon fishbone nanowires
Authors: Maire Jeremie , Anufriev Roman , Hori Takuma , Shiomi Junichiro , Volz Sebastian , Nomura Masahiro 
Published: March 2018

AbstractSemiconductor nanowires are potential building blocks for future thermoelectrics because of their low thermal conductivity. Recent theoretical works suggest that thermal conductivity of nanowires can be further reduced by additional constrictions, pillars or wings. Here, we experimentally study heat conduction in silicon nanowires with periodic wings, called fishbone nanowires. We find that like in pristine nanowires, the nanowire cross-section controls thermal conductivity of fishbone nanowires. However, the periodic wings further reduce the thermal conductivity. Whereas an increase in the wing width only slightly affects the thermal conductivity, an increase in the wing depth clearly reduces thermal conductivity, and this reduction is stronger in the structures with narrower nanowires. Our experimental data is supported by the Callaway-Holland model, finite element modelling and phonon transport simulations.
Development and validation of the Canine Reward Responsiveness Scale –Examining individual differences in reward responsiveness of the domestic dog
Authors: Gerencsér Linda , Bunford Nóra , Moesta Alexandra , Miklósi Ádám 
Published: March 2018

AbstractAlthough there is ample data indicating that reward processing plays an important role in human psychopathologies and pharmaco- and psychotherapy treatment response, the corresponding animal-model research needs to be extended to models whose motivational and social dispositions are better generalizable than those of the traditional models. Accordingly, our aim was to develop and assess the reliability and validity of an owner-report rating scale of reward responsiveness in domestic dogs (N = 2149) and then to examine individual differences in reward responsiveness. Responsiveness was categorisable by reward type (ball/toy and food) and exhibited individual variability manifesting in age- and breed-related differences. Rating scale scores were associated with behavioural observation of reward processing, indicating evidence of convergent validity. Ball/toy and food reward responsiveness were associated with owner-rated hyperactivity-impulsivity‚ inattention and with differences in training, indicating evidence of concurrent validity. Extreme (vs. average) reward responsiveness was also predicted by dogs’ hyperactivity-impulsivity and inattention‚ and extreme responsiveness was associated with increased likelihood of physical health and/or social problems. These findings are informative with regard to the dog as an animal model for various human behavioural and cognitive functions‚ and also for the dog in its own right as they are relevant to training and welfare.
Direct coupling of detergent purified human mGlu5 receptor to the heterotrimeric G proteins Gq and Gs
Authors: Nasrallah Chady , Rottier Karine , Marcellin Romain , Compan Vincent , Font Joan , Llebaria Amadeu , Pin Jean-Philippe , Banères Jean-Louis , Lebon Guillaume 
Published: March 2018

AbstractThe metabotropic glutamate (mGlu) receptors are class C G protein-coupled receptors (GPCRs) that modulate synaptic activity and plasticity throughout the mammalian brain. Signal transduction is initiated by glutamate binding to the venus flytrap domains (VFT), which initiates a conformational change that is transmitted to the conserved heptahelical domains (7TM) and results ultimately in the activation of intracellular G proteins. While both mGlu1 and mGlu5 activate Gαq G-proteins, they also increase intracellular cAMP concentration through an unknown mechanism. To study directly the G protein coupling properties of the human mGlu5 receptor homodimer, we purified the full-length receptor, which required careful optimisation of the expression, N-glycosylation and purification. We successfully purified functional mGlu5 that activated the heterotrimeric G protein Gq. The high-affinity agonist-PAM VU0424465 also activated the purified receptor in the absence of an orthosteric agonist. In addition, it was found that purified mGlu5 was capable of activating the G protein Gs either upon stimulation with VU0424465 or glutamate, although the later induced a much weaker response. Our findings provide important mechanistic insights into mGlu5 G protein-dependent activity and selectivity.
Bio-derived three-dimensional hierarchical carbon-graphene-TiO2 as electrode for supercapacitors
Authors: Jiang Lili , Ren Zhifeng , Chen Shuo , Zhang Qinyong , Lu Xiong , Zhang Hongping , Wan Guojiang 
Published: March 2018

AbstractThis paper reports a novel loofah-derived hierarchical scaffold to obtain three-dimensional biocarbon-graphene-TiO2 (BC-G-TiO2) composite materials as electrodes for supercapacitors. The loofah scaffold was first loaded with G and TiO2 by immersing, squeezing, and loosening into the mixed solution of graphene oxide and titania, and then carbonized at 900 °C to form the BC-G-TiO2 composite. The synergistic effects of the naturally hierarchical biocarbon structure, graphene, and TiO2 nanoparticles on the electrochemical properties are analyzed. The biocarbon provides a high interconnection and an easy accessibility surface for the electrolyte. Graphene bridged the BC and TiO2 nanoparticles, improved the conductivity of the BC-G-TiO2 composite, and increased the electron transfer efficiency. TiO2 nanoparticles also contributed to the pesudocapacitance and electrochemical stability.
Selection of reference genes for miRNA qRT-PCR under abiotic stress in grapevine
Authors: Luo Meng , Gao Zhen , Li Hui , Li Qin , Zhang Caixi , Xu Wenping , Song Shiren , Ma Chao , Wang Shiping 
Published: March 2018

AbstractGrapevine is among the fruit crops with high economic value, and because of the economic losses caused by abiotic stresses, the stress resistance ofVitis viniferahas become an increasingly important research area. Among the mechanisms responding to environmental stresses, the role of miRNA has received much attention recently. qRT-PCR is a powerful method for miRNA quantitation, but the accuracy of the method strongly depends on the appropriate reference genes. To determine the most suitable reference genes for grapevine miRNA qRT-PCR, 15 genes were chosen as candidate reference genes. After eliminating 6 candidate reference genes with unsatisfactory amplification efficiency, the expression stability of the remaining candidate reference genes under salinity, cold and drought was analysed using four algorithms, geNorm, NormFinder, deltaCt and Bestkeeper. The results indicated thatU6 snRNAwas the most suitable reference gene under salinity and cold stresses; whereasmiR168was the best for drought stress. The best reference gene sets for salinity, cold and drought stresses weremiR160e + miR164a,miR160e + miR168andACT + UBQ + GAPDH, respectively. The selected reference genes or gene sets were verified usingmiR319ormiR408as the target gene.
Macular Choroidal Small-Vessel Layer, Sattler’s Layer and Haller’s Layer Thicknesses: The Beijing Eye Study
Authors: Zhao Jing , Wang Ya Xing , Zhang Qi , Wei Wen Bin , Xu Liang , Jonas Jost B. 
Published: March 2018

AbstractTo study macular choroidal layer thickness, 3187 study participants from the population-based Beijing Eye Study underwent spectral-domain optical coherence tomography with enhanced depth imaging for thickness measurements of the macular small-vessel layer, including the choriocapillaris, medium-sized choroidal vessel layer (Sattler’s layer) and large choroidal vessel layer (Haller’s layer). In multivariate analysis, greater thickness of all three choroidal layers was associated (all P < 0.05) with higher prevalence of age-related macular degeneration (AMD) (except for geographic atrophy), while it was not significantly (all P > 0.05) associated with the prevalence of open-angle glaucoma or diabetic retinopathy. There was a tendency (0.07 > P > 0.02) toward thinner choroidal layers in chronic angle-closure glaucoma. The ratio of small-vessel layer thickness to total choroidal thickness increased (P < 0.001; multivariate analysis) with older age and longer axial length, while the ratios of Sattler’s layer and Haller’s layer thickness to total choroidal thickness decreased. A higher ratio of small-vessel layer thickness to total choroidal thickness was significantly associated with a lower prevalence of AMD (early type, intermediate type, late geographic type). Axial elongation-associated and aging-associated choroidal thinning affected Haller’s and Sattler’s layers more markedly than the small-vessel layer. Non-exudative and exudative AMD, except for geographic atrophy, was associated with slightly increased choroidal thickness.
The role of combining medroxyprogesterone 17-acetate with human menopausal gonadotropin in mouse ovarian follicular development
Authors: Wen Xiaowei , Xie Jun , Zhou Lixia , Fan Yong , Yu Baofeng , Chen Qiuju , Fu Yonglun , Yan Zheng , Guo Haiyan , Lyu Qifeng , Kuang Yanping , Chai Weiran 
Published: March 2018

AbstractMedroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However, the molecular mechanism of MPA + hMG treatment in follicular development is poorly described. Here we performed a study to investigate the impact of MPA + hMG on ovarian stimulation utilizing a mouse model in vivo. Forty female BALB/C mice were randomly divided into four groups of 10 each and treated during ciestrus stage and continued for 5 days: control group, MPA group, hMG group, and MPA + hMG group. Morphological and molecular biology methods were used for detecting serum hormones and ovarian function. MPA + hMG group exhibited increasing follicle stimulating hormone (FSH), antral follicle, FSH receptor (FSHR) and phosphorylated mammal target of rapamycin (p-mTOR), and decreasing luteinizing hormone (LH), estradiol (E2), progesterone (P), corpus luteum, phosphoinositide 3-kinase (PI3K), Akt and mTOR compared with control group. In contrast, MPA + hMG group showed reduced FSH, LH, E2, P, corpus luteum, LH receptor (LHR), and activated PI3K,/Akt/mTOR pathway compared with hMG group (P < 0.05). Collectively, these data definitively established that MPA plus hMG may modulate the hormone, hormone receptor and PI3K/Akt/mTOR signaling pathway to influence follicular development in the mouse ovary. Our study provides overwhelming support for MPA + hMG as an effective treatment for infertility in women.
Chemical composition and hepatoprotective effect of free phenolic extract from barley during malting process
Authors: Quan Meiping , Li Qin , Zhao Pei , Tian Chengrui 
Published: March 2018

AbstractIn this study, No.Ganpi4 of barley was steeped and malted to investigate the changes of phenolic compounds during malting process. The free phenolic extract from raw barley (FPEB) was analyzed by HPLC and predominant compounds were (+)-catechin, protocatechuate and quercetin. The FPEB was evaluated for hepatoprotective effect in vivo and in vitro. Intragastric administration of FPEB (100, 200 and 400 mg/kg/bw) to mice significantly weakened the effects of hepatic damage induced by CCl4 toxicity on serum markers, including serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total-bilirubin, total cholesterol and total triglycerides. FPEB administration also increased the hepatic levels of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. Histopathological examinations further confirmed that FPEB could protect the liver from CCl4-induced damage. In vitro, the experimental results demonstrated that FPEB could reduce BRL hepatocyte apoptosis and damage induced by CCl4. These results suggest that FPEB exerts an effective protection for hepatic injury, and barley has the potential as a functional food to prevent hepatic injury.