bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switchable genome editing via genetic code expansion
Authors: Suzuki Toru , Asami Maki , Patel Sanjay G. , Luk Louis Y. P. , Tsai Yu-Hsuan , Perry Anthony C. F. 
Published: June 2018

AbstractMultiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges.
The Association between Daytime Napping Characteristics and Bone Mineral Density in Elderly Thai Women without Osteoporosis
Authors: Saetung Sunee , Reutrakul Sirimon , Chailurkit La-or , Rajatanavin Rajata , Ongphiphadhanakul Boonsong , Nimitphong Hataikarn 
Published: June 2018

AbstractLow bone mass is more prevalent with increasing age. Studies have found associations between sleep duration, sleep quality and obstructive sleep apnea and bone mineral density (BMD). However, less is known about the relationship between daytime napping and BMD. We aimed to investigate the association between daytime napping and BMD in elderly Thai women. Demographic data, lifestyle information and sleep characteristics were obtained by interviewing 387 elderly women. Weight and height were measured. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay. BMD was measured by dual-energy X-ray absorptiometry (DXA). Higher BMI and having type 2 diabetes (T2DM) were correlated with higher lumbar spine 2–4 (L2-4) BMD, while younger age, higher BMI and higher serum 25(OH)D level were correlated with higher femoral neck (FN) and total hip (TH) BMD. After adjusting for age, age at menopause, BMI, 25(OH)D level and T2DM, a higher frequency of weekly daytime napping was associated with lower FN and TH BMD but not at L2-4 BMD. Additionally, longer daytime napping duration was negatively associated with BMD at TH. In summary higher frequency and longer duration of daytime napping are associated with lower femoral BMD in elderly women. Mechanisms underlying these associations should be further explored.
Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1
Authors: Rexen Ulven Elisabeth , Trauelsen Mette , Brvar Matjaz , Lückmann Michael , Bielefeldt Line Ø. , Jensen Lisa K. I. , Schwartz Thue W. , Frimurer Thomas M. 
Published: June 2018

AbstractThe succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.
Dual role of HDAC10 in lysosomal exocytosis and DNA repair promotes neuroblastoma chemoresistance
Authors: Ridinger Johannes , Koeneke Emily , Kolbinger Fiona R. , Koerholz Katharina , Mahboobi Siavosh , Hellweg Lars , Gunkel Nikolas , Miller Aubry K. , Peterziel Heike , Schmezer Peter , Hamacher-Brady Anne , Witt Olaf , Oehme Ina 
Published: June 2018

AbstractDrug resistance is a leading cause for treatment failure in many cancers, including neuroblastoma, the most common solid extracranial childhood malignancy. Previous studies from our lab indicate that histone deacetylase 10 (HDAC10) is important for the homeostasis of lysosomes, i.e. acidic vesicular organelles involved in the degradation of various biomolecules. Here, we show that depleting or inhibiting HDAC10 results in accumulation of lysosomes in chemotherapy-resistant neuroblastoma cell lines, as well as in the intracellular accumulation of the weakly basic chemotherapeutic doxorubicin within lysosomes. Interference with HDAC10 does not block doxorubicin efflux from cells via P-glycoprotein inhibition, but rather via inhibition of lysosomal exocytosis. In particular, intracellular doxorubicin does not remain trapped in lysosomes but also accumulates in the nucleus, where it promotes neuroblastoma cell death. Our data suggest that lysosomal exocytosis under doxorubicin treatment is important for cell survival and that inhibition of HDAC10 further induces DNA double-strand breaks (DSBs), providing additional mechanisms that sensitize neuroblastoma cells to doxorubicin. Taken together, we demonstrate that HDAC10 inhibition in combination with doxorubicin kills neuroblastoma, but not non-malignant cells, both by impeding drug efflux and enhancing DNA damage, providing a novel opportunity to target chemotherapy resistance.
Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences
Authors: Li Han , Sun Fengzhu 
Published: June 2018

AbstractPredicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.
Estimation of chimpanzee age based on DNA methylation
Authors: Ito Hideyuki , Udono Toshifumi , Hirata Satoshi , Inoue-Murayama Miho 
Published: June 2018

AbstractIn wild animal conservation, knowing the age of an individual animal is extremely beneficial. However, estimating the age is difficult for many species. Recently, epigenetics-based methods of estimating age have been reported. These studies were predominantly on humans with few reports on other animals, especially wild animals. In the present study, a chimpanzee (Pan troglodytes) age prediction model was developed based on the ELOVL2, CCDC102B, and ZNF423 genes that may also have application in human age prediction. Pyrosequencing was used to measure methylation in 20 chimpanzee blood samples and correlation between age and methylation status was calculated. Age and methylation of sites in ELOVL2 and CCDC102B were significantly correlated and an age prediction model was created using these genes. In the regression equation using only ELOVL2, the highest correlation coefficient was 0.741, with a mean absolute deviation (MAD) of 5.41, compared with the combination of ELOVL2 and CCDC102B, where the highest correlation coefficient was 0.742 and the MAD was 5.41. Although larger MADs were observed in chimpanzees than in humans based on these genes, the results indicate the feasibility of estimating chimpanzee age using DNA methylation, and can have implications in understanding the ecology of chimpanzees and chimpanzee conservation.
Detection of the Cell Cycle-Regulated Negative Feedback Phosphorylation of Mitogen-Activated Protein Kinases in Breast Carcinoma using Nanofluidic Proteomics
Authors: Urasaki Yasuyo , Fiscus Ronald R. , Le Thuc T. 
Published: June 2018

AbstractMitogen-activated protein kinases (MAPKs) play an important role in the regulation of cell proliferation, oncogenic transformation, and drug resistance. This study examined the capability of nanofluidic proteomics to identify aberrations in the MAPK signaling cascade, monitor its drug response, and guide the rational design of intervention strategies. Specifically, the protein post-translational modification (PTM) profiles of MEK1, MEK2, and ERK1/2 were measured in breast carcinoma and breast cancer cell lines. Nanofluidic proteomics revealed hyper-phosphorylation of MAPKs in breast carcinoma and breast cancer cells treated with kinase inhibitors that interfere with cell cycle regulation, such as dinaciclib, an inhibitor of cyclin-dependent kinases, and rigosertib, an inhibitor of polo-like kinase 1. A pMEK1 (Thr286) phosphor-isoform, which serves as a biomarker of cell cycle-regulated negative feedback phosphorylation in breast cancer cells, was detected in breast carcinoma. Inhibition of the MAPK pathway with dabrafenib, a B-Raf inhibitor, or trametinib, a MEK1/2 inhibitor, suppressed both the positively regulated phosphorylation of MAPKs and the negatively regulated phosphorylation of MEK1. Interestingly, the combinations of dabrafenib and rigosertib or trametinib and rigosertib permitted the suppression of positively regulated MAPK phosphorylation together with the promotion of negatively regulated MEK1 phosphorylation. The effectiveness of protein PTM-guided drug combinations for inhibition of the MAPK pathway remains to be experimentally tested. Via protein PTM profiling, nanofluidic proteomics provides a robust means to detect anomalies in the MAPK signaling cascade, monitor its drug response, and guide the possible design of drug combinations for MAPK pathway-focused targeting.
Coherent backscattering in quasi-ballistic ultra-high mobility GaAs/AlGaAs 2DES
Authors: Samaraweera R. L. , Liu H.-C. , Gunawardana B. , Kriisa A. , Reichl C. , Wegscheider W. , Mani R. G. 
Published: June 2018

AbstractA small and narrow negative-magnetoresistance (MR) effect that appears about null magnetic field over the interval −0.025 ≤ B ≤ 0.025 T in magnetotransport studies of the GaAs/AlGaAs 2D system with μ ≈ 107cm2/Vs is experimentally examined as a function of the sample temperature, T. The temperature dependent magnetoresistance data were fit using the Hikami et al. theory, without including the spin-orbit correction, to extract the inelastic length, li, which decreases rapidly with increasing temperature. It turns out that li < le, where le is the elastic length, for all T. Thus, we measured the single particle lifetime, τs, and the single particle mean free path ls = vFτs. A comparison between li and ls indicates that li > ls. The results suggest that the observed small and narrow magnetoresistance effect about null magnetic field could be a manifestation of coherent backscattering due to small angle scattering from remote ionized donors in the high mobility GaAs/AlGaAs 2DES.
ChemDIS-Mixture: an online tool for analyzing potential interaction effects of chemical mixtures
Authors: Tung Chun-Wei , Wang Chia-Chi , Wang Shan-Shan , Lin Pinpin 
Published: June 2018

AbstractThe assessment of bioactivity and toxicity for mixtures remains a challenging work. Although several computational models have been developed to accelerate the evaluation of chemical-chemical interaction, a specific biological endpoint should be defined before applying the models that usually relies on clinical and experimental data. The development of computational methods is desirable for identifying potential biological endpoints of mixture interactions. To facilitate the identification of potential effects of mixture interactions, a novel online system named ChemDIS-Mixture is proposed to analyze the shared target proteins, and common enriched functions, pathways, and diseases affected by multiple chemicals. Venn diagram tools have been implemented for easy analysis and visualization of interaction targets and effects. Case studies have been provided to demonstrate the capability of ChemDIS-Mixture for identifying potential effects of mixture interactions in clinical studies. ChemDIS-Mixture provides useful functions for the identification of potential effects of coexposure to multiple chemicals. ChemDIS-Mixture is freely accessible at http://cwtung.kmu.edu.tw/chemdis/mixture.
Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets
Authors: Wei Hao , Malcor Jean-Daniel M. , Harper Matthew T. 
Published: June 2018

AbstractPlatelets protect the vascular system during damage or inflammation, but platelet activation can result in pathological thrombosis. Activated platelets release a variety of extracellular vesicles (EVs). EVs shed from the plasma membrane often expose phosphatidylserine (PS). These EVs are pro-thrombotic and increased in number in many cardiovascular and metabolic diseases. The mechanisms by which PS-exposing EVs are shed from activated platelets are not well characterised. Cholesterol-rich lipid rafts provide a platform for coordinating signalling through receptors and Ca2+channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca2+-triggered release of PS-exposing EVs. Although calpain activity was required for release of PS-exposing, calpain-dependent cleavage of talin was not affected by cholesterol depletion. P2Y12and TPα, receptors for ADP and thromboxane A2, respectively, have been reported to be in platelet lipid rafts. However, the P2Y12antagonist, AR-C69931MX, or the cyclooxygenase inhibitor, aspirin, had no effect on A23187-induced release of PS-exposing EVs. Together, these data show that lipid rafts are required for release of PS-exposing EVs from platelets.
Female Japanese quail visually differentiate testosterone-dependent male attractiveness for mating preferences
Authors: Hiyama Gen , Mizushima Shusei , Matsuzaki Mei , Tobari Yasuko , Choi Jae-Hoon , Ono Takashi , Tsudzuki Masaoki , Makino Satoshi , Tamiya Gen , Tsukahara Naoki , Sugita Shoei , Sasanami Tomohiro 
Published: June 2018

AbstractBiased mating due to female preferences towards certain traits in males is a major mechanism driving sexual selection, and may constitute an important evolutionary force in organisms with sexual reproduction. In birds, although the role of male ornamentation, plumage coloration, genetic dissimilarity, and body size have on mate selection by females have been examined extensively, few studies have clarified exactly how these characteristics affect female mate preferences. Here, we show that testosterone (T)-dependent male attractiveness enhances female preference for males of a polygamous species, the Japanese quail. A significant positive correlation between female mating preference and circulating T in the male was observed. The cheek feathers of attractive males contained higher levels of melanin and were more brightly colored. The ability of females to distinguish attractive males from other males was negated when the light source was covered with a sharp cut filter (cutoff; < 640 nm). When females were maintained under short-day conditions, the expression of retinal red-sensitive opsin decreased dramatically and they became insensitive to male attractiveness. Our results showed that female preference in quail is strongly stimulated by male feather coloration in a T-dependent manner and that female birds develop a keen sense for this coloration due to upregulation of retinal red-sensitive opsin under breeding conditions.
High level of IgG4 as a biomarker for a new subset of inflammatory bowel disease
Authors: Wang Zhujun , Zhu Min , Luo Chengxin , zhen Yu , Mu Jingxi , Zhang Wenyan , Ouyang Qin , Zhang Hu 
Published: June 2018

AbstractThe roles of B and plasma cells in the pathogenesis of inflammatory bowel disease (IBD) are largely unrevealed. Data on the characteristics of IgG4 in patients with IBD are scarce. In this case-control study, serum IgG4 levels were comparable between patients with IBD and healthy individuals, whereas patients with IBD had dramatically higher mucosal IgG4 counts than healthy individuals. In patients with UC, mucosal IgG4 counts were positively correlated with serum IgG4 levels, serum IgG4/IgG ratios, and the Mayo Index; serum IgG4 levels and IgG4/IgG ratios were associated with a history of intestinal surgery and medications. A significant mucosal IgG4 count was found in 33.3% of patients with IBD, whereas, elevated serum IgG4 levels were found in only 9.9% of patients with IBD. Lesions were more severe and extensive in IBD patients with high levels of serum and mucosal IgG4. High levels of serum and mucosal IgG4 decreased after treatment with glucocorticoids or other immunosuppressants. High IgG4 level may be a biomarker for a new subset of IBD. More studies are warranted to explore this new subset of IBD for personalized therapy in the future.
Elimination of all redundant climbing fiber synapses requires granule cells in the postnatal cerebellum
Authors: Bailly Yannick , Rabacchi Sylvia , Sherrard Rachel M. , Rodeau Jean-Luc , Demais Valérie , Lohof Ann M. , Mariani Jean 
Published: June 2018

AbstractDifferent afferent synapse populations interact to control the specificity of connections during neuronal circuit maturation. The elimination of all but one climbing-fiber onto each Purkinje cell during the development of the cerebellar cortex is a particularly well studied example of synaptic refinement. The suppression of granule cell precursors by X irradiation during postnatal days 4 to 7 prevents this synaptic refinement, indicating a critical role for granule cells. Several studies of cerebellar development have suggested that synapse elimination has a first phase which is granule cell-independent and a second phase which is granule cell-dependent. In this study, we show that sufficiently-strong irradiation restricted to postnatal days 5 or 6 completely abolishes climbing fiber synaptic refinement, leaving the olivo-cerebellar circuit in its immature configuration in the adult, with up to 5 climbing fibers innervating the Purkinje cell in some cases. This implies that the putative early phase of climbing fiber synapse elimination can be blocked by irradiation-induced granule cell loss if this loss is sufficiently large, and thus indicates that the entire process of climbing fiber synapse elimination requires the presence of an adequate number of granule cells. The specific critical period for this effect appears to be directly related to the timing of Purkinje cell and granule cell development in different cerebellar lobules, indicating a close, spatiotemporal synchrony between granule-cell development and olivo-cerebellar synaptic maturation.
The Use of Monoclonal Antibodies to Human Platelet Membrane Glycoprotein IIb-IIIa to Quantitate Platelet Deposition on Artificial Surfaces
Authors: Mulvihill Juliette N , Huisman Han G , Cazenave Jean-Pierre , van Mourik Jan A , van Aken Willem G 
Published: June 2018

SummaryA new technique is described to quantitate platelet deposition in vitro on artifical surfaces, based on a surface phase radioimmunoassay using the monoclonal antibody 6C9, directed specifically against the membrane glycoprotein complex IIb-IIIa of human platelets. Results correlate in linear fashion with those obtained using 111Indium labeled platelets. The method offers particular advantages for the measurement of platelet deposition in whole blood, since platelet separation, washing and labeling procedures are eliminated, together with the ensuing possible selection of platelet populations. In vitro perfusion is performed in glass capillaries of precisely defined diameter (0.80 or 0.56 mm i.d.). Blood flow is laminar and accurately controlled over wall shear rates ranging from venous to capillary (50-4,000 s-1). Using glass capillaries precoated with purified human albumin or fibrinogen or bovine collagen, platelet deposition from suspensions of washed human platelets in Tyrode's-albumin buffer in the presence of a 40% hematocrit is (platelets/mm2): 11,000 (albumin), 78,000 (fibrinogen) and 306,000 (collagen) after 5 min perfusion at 2,000 s-1. In heparin, citrate or hirudin anticoagulated whole blood, surfaces are passivated, probably by albumin adsorption from plasma (platelets/mm2): 400 (albumin), 3,600 (fibrinogen) and 48,000 (collagen) after 5 min perfusion in the presence of 13 mM citrate.
Effet du Bromure de 2-Amino-Ethylisothiouronium (AET) sur l’Hémocoagulation
Authors: Praga C , Jean G , Ferrone S 
Published: June 2018

RésuméL’AET en solution aqueuse et à un pH physiologique se transforme en MEG.Les groupes –SH de ce produit agissent sur plusieurs facteurs procoagulants et anticoagulants. La réaction prothrombine-thrombine paraît particulièrement inhibée tandis que la réaction fibrinogène tllrombir→ fibrine ne l’est que faiblement. La transformation de la prothrombine en thrombine est influencée par le temps de contact du plasma avec L’AET et par la concentration d’AET. Les antithrombines semblent progressivement inhibées par des doses croissantes d’AET. L’augmentation de la constante « Am » du thromboélastogramme fait envisager une action de l’AET sur le LLF (Laki-Lorand factor). Le temps de lyse du caillot est allongé par des doses importantes d’AET.Enfin FAET ne modifie pas la rétraction du caillot et l’adhésivité plaquettaire.
The Plasminogen Content of Thrombi
Authors: Ogston D , Ogston C. M , Fullerton H. W 
Published: June 2018

Summary1. The plasminogen content of serum and plasma does not differ. The serum remaining after the production of an in vitro artificial thrombus has a plasminogen content similar to the original plasma. Direct measurement of the plasminogen content of artificial thrombi confirms that little plasminogen is adsorbed onto fibrin during the process of clotting.2. The lysis of pre-formed artificial thrombi by urokinase is substantially increased in the presence of plasma. This is not due to free plasmin in the medium surrounding the thrombus.3. Partially purified plasminogen is adsorbed onto artificial thrombi endowing them with the capacity to lyse on the addition of urokinase. In contrast plasminogen from plasma or serum is not adsorbed onto thrombi.4. We suggest that the lysis of a thrombus results from diffusion of circulating plasminogen into the thrombus and its interaction with activator on the surface of the fibrin fibrils with consequent plasmin formation.
Comparative Research on the Fibrinolytic Action of Different Nicotinic Acid Derivatives Following Their Prolonged Administration into Rabbits
Authors: de Nicola P , Gibelli A , Turazza G 
Published: June 2018

SummarySix different nicotinic acid derivatives were given intravenously into rabbits for 28 days. The dosage was calculated on the basis of equivalents of nicotinic acid. Fibrinolytic activity in plasma was studied by means of the fibrin plate method (heated plates; euglobulinic precipitate, with and without the addition of activator). Plasmin and plasminogen activities were evaluated. The most significant results concern the differences in duration, intensity and type (plasmin and/or plasminogen increase) of effect of the different nicotinic acid derivatives.