bluuebunny/crossref_metadata_2025_split huggingface dataset:
CREATE-X a role for capecitabine in early-stage breast cancer: an analysis of available data
Authors: Zujewski Jo Anne , Rubinstein Lawrence 
Published: July 2017

AbstractBreast cancer patients with residual disease after neoadjuvant chemotherapy and surgery may benefit from additional anti-cancer therapies. Capecitabine, an oral antimetabolite and prodrug of 5-Flurouracil, has been approved for treating metastatic breast cancer. One randomized clinical trial (CREATE-X) of capecitabine versus no additional therapy has been conducted in women with early stage breast cancer who received standard chemotherapy pre-operative therapy and had residual invasive breast cancer at the time of surgery. Results from CREATE-X, showed that capecitabine had a statistically significant survival advantage compared with no additional therapy. This perspective provides a review and analysis of the available data from CREATEx in the context of results from other adjuvant trials of capecitabine in early stage breast cancer that had disease–free survival as a primary endpoint. We conclude that although the previously published studies of capecitabine in the adjuvant setting did not meet their primary endpoint, the data from these studies are consistent with the hypothesis that capecitabine may offer additional survival benefit in patients with chemo-refractory breast cancer at the time of surgery after receiving standard chemotherapy. In these patients, offering a course of adjuvant capecitabine or enrolling the patient in a clinical trial are appropriate therapeutic options. The patient should be informed about both the increased survival observed in the CREATEx trial and the expected toxicities from capecitabine chemotherapy.
A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA
Authors: Lake Blue B. , Codeluppi Simone , Yung Yun C. , Gao Derek , Chun Jerold , Kharchenko Peter V. , Linnarsson Sten , Zhang Kun 
Published: July 2017

AbstractSignificant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell’s transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.
A positive feedback loop mediated by Sigma X enhances expression of the streptococcal regulator ComR
Authors: Khan Rabia , Junges Roger , Åmdal Heidi A. , Chen Tsute , Morrison Donald A. , Petersen Fernanda C. 
Published: July 2017

AbstractNatural transformation is used by bacteria to take up DNA from their surroundings and incorporate it into their genomes. Streptococci do so during a transient period of competence, triggered by pheromones that they produce, secrete and sense under conditions influenced by the environment. In Streptococcus mutans, Streptococcus suis, and species of the bovis, salivarius and pyogenic groups of streptococci, the pheromone XIP is sensed by the intra-cellular regulator ComR, that in turn activates the transcription of comS, encoding the XIP precursor, and of sigX, encoding the only known alternative sigma factor in streptococci. Although induction of comR during competence has been known for more than fifteen years, the mechanism regulating its expression remains unidentified. By a combination of directional RNA-sequencing, optimal competence conditions, stepwise deletions and marker-less genome editing, we found that SigX is the missing link in overproduction of ComR. In the absence of comR induction, both sigX expression and transformation were significantly reduced. Placing comR and comS transcripts under the control of different regulators so as to form two interlocked positive feedback circuits may enable S. mutans to fine-tune the kinetics and magnitude of the competence response according to their need.
Superior non-specific motor learning in the blind
Authors: Morin-Parent Florence , de Beaumont Louis , Théoret Hugo , Lepage Jean-Francois 
Published: July 2017

AbstractIt is well established that blindness induces changes in cerebral function and structure, namely affecting the somatomotor regions. However, the behavioural significance of these changes on the motor system, and on motor learning in particular, remains elusive. In this study, we used a modified version of the serial reaction time task (SRTT) with auditory cues to assess sequence specific and non-specific motor learning in blind adults and sighted controls, and compare them with sighted controls performing the classic visual SRTT. Our results show that the auditory SRTT faithfully replicates the typical learning pattern obtained with the visual SRTT. On the auditory SRTT, blind individuals consistently showed faster reaction times than sighted controls, being at par with sighted individuals performing the visual SRTT. On the other hand, blind participants displayed a particular pattern of motor learning in comparison to both sighted groups; while controls improved prominently on sequence specific learning, blind individuals displayed comparable performance on both specific and non-specific learning, markedly outperforming the control groups on non-specific learning. These results show that blindness, in addition to causing long-term changes in cortical organisation, can also influence dynamic neuroplastic mechanisms in systems beyond those typically associated with compensatory sensory processing.
Observation of aggregation triggered by Resonance Energy Transfer (RET) induced intermolecular pairing force
Authors: Pan Xiaoyong , Wang Weizhi , Ke Lin , Zhang Nan 
Published: July 2017

AbstractIn this report, we showed the existence of RET induced intermolecular pairing force by comparing their fluorescence behaviors under room illumination vs standing in dark area for either PFluAnt solution or PFluAnt&PFOBT mixture. Their prominent emission attenuation under room illumination brought out the critical role of photo, i.e. RET induced intermolecular pairing force in induction of polymer aggregation. Constant UV-Vis absorption and fluorescence spectra in terms of both peak shapes and maximum wavelengths implied no chemical decomposition was involved. Recoverable fluorescence intensity, fluorescence lifetime as well as NMR spectra further exclude photo induced decomposition. The controllable on/off state of RET induced intermolecular pairing force was verified by the masking effect of outside PFluAnt solution which function as filter to block the excitation of inside PFluAnt and thus off the RET induced intermolecular pairing force. Theoretical calculation suggest that magnitude of RET induced intermolecular pairing force is on the same scale as that of van der Waals interaction. Although the absolute magnitude of RET induced intermolecular pairing force was not tunable, its effect can be magnified by intentionally turn it “on”, which was achieved by irradiance with 5 W desk lamp in this report.
Superhydrophobic Drag-Reduction Spherical Bearing Fabricated by Laser Ablation and PEI Regulated ZnO Nanowire Growth
Authors: Weng Rui , Zhang Haifeng , Tuo Yanjing , Wang Yang , Liu Xiaowei 
Published: July 2017

AbstractThe resistance of the bearing is a significant factor affecting the performance of the ball-disk rotor gyroscope. The micro and nano combined surface with low surface energy material modifications can be hydrophobic. This can reduce the drag when the bearing is lubricated by deionized water. Laser ablation method is utilized to form micron-scaled structures on the surface of the stainless steel rotor ball. And the nanostructures are formed by PEI (Polyetherimide) regulated ZnO nanowires growth. After low surface energy material modification, the water contact angle of processed surface was 163° and the sliding angle was less than 4°. The maximum rotational speed was enhanced by up to 82.77% at 1.5 W driving power. Experiments show that the superhydrophobic drag-reduction spherical bearing has good short-term reliability. At 5 V drive voltage, the bearing can extend the rotational speed of ball-disk rotor gyroscope to 35000 rpm, and maintain the normal operation for longer than 40 minutes. This is quite meaningful for short-term-work or one-time-use rotor gyroscopes.
Identification of a T cell gene expression clock obtained by exploiting a MZ twin design
Authors: Remondini Daniel , Intrator Nathan , Sala Claudia , Pierini Michela , Garagnani Paolo , Zironi Isabella , Franceschi Claudio , Salvioli Stefano , Castellani Gastone 
Published: July 2017

AbstractMany studies investigated age-related changes in gene expression of different tissues, with scarce agreement due to the high number of affecting factors. Similarly, no consensus has been reached on which genes change expression as a function of age and not because of environment. In this study we analysed gene expression of T lymphocytes from 27 healthy monozygotic twin couples, with ages ranging over whole adult lifespan (22 to 98 years). This unique experimental design allowed us to identify genes involved in normative aging, which expression changes independently from environmental factors. We obtained a transcriptomic signature with 125 genes, from which chronological age can be estimated. This signature has been tested in two datasets of same cell type hybridized over two different platforms, showing a significantly better performance compared to random signatures. Moreover, the same signature was applied on a dataset from a different cell type (human muscle). A lower performance was obtained, indicating the possibility that the signature is T cell-specific. As a whole our results suggest that this approach can be useful to identify age-modulated genes.
Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
Authors: Gamazon Eric R. , Konkashbaev Anuar , Derks Eske M. , Cox Nancy J. , Lee Younghee 
Published: July 2017

AbstractWe performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome.
Antifungal treatment of wild amphibian populations caused a transient reduction in the prevalence of the fungal pathogen, Batrachochytrium dendrobatidis
Authors: Geiger Corina C. , Bregnard Cindy , Maluenda Elodie , Voordouw Maarten J. , Schmidt Benedikt R. 
Published: July 2017

AbstractEmerging infectious diseases can drive host populations to extinction and are a major driver of biodiversity loss. Controlling diseases and mitigating their impacts is therefore a priority for conservation science and practice. Chytridiomycosis is a devastating disease of amphibians that is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), and for which there is an urgent need to develop mitigation methods. We treated tadpoles of the common midwife toad (Alytes obstetricans) with antifungal agents using a capture-treat-release approach in the field. Antifungal treatment during the spring reduced the prevalence of Bd in the cohort of tadpoles that had overwintered and reduced transmission of Bd from this cohort to the uninfected young-of-the-year cohort. Unfortunately, the mitigation was only transient, and the antifungal treatment was unable to prevent the rapid spread of Bd through the young-of-the year cohort. During the winter, Bd prevalence reached 100% in both the control and treated ponds. In the following spring, no effects of treatment were detectable anymore. We conclude that the sporadic application of antifungal agents in the present study was not sufficient for the long-term and large-scale control of Bd in this amphibian system.
Plasmodium berghei P47 is essential for ookinete protection from the Anopheles gambiae complement-like response
Authors: Ukegbu Chiamaka Valerie , Giorgalli Maria , Yassine Hassan , Ramirez Jose Luis , Taxiarchi Chrysanthi , Barillas-Mury Carolina , Christophides George K. , Vlachou Dina 
Published: July 2017

AbstractMalaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P. berghei P47 in Anopheles gambiae mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of P. berghei P47 in vivo and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.
PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
Authors: Luo Li-Da , Li Gang , Wang Yun 
Published: July 2017

AbstractSynapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines. On the contrary, loss of function of PLD1, including overexpression of the catalytically-inactive PLD1 (PLD1ci) or knocking down PLD1 by siRNAs, leads to reduction in the spine density and the spine area. Moreover, we found that PLD1 promotes the dendritic spine development via regulating the membrane level of N-cadherin. Further studies showed that the regulation of surface N-cadherin by PLD1 is related with the cleavage of N-cadherin by a member of the disintegrin and metalloprotease family-ADAM10. Taking together, our results indicate a positive role of PLD1 in synaptogenesis by inhibiting the ADAM10 mediated N-cadherin cleavage and provide new therapeutic clues for some neurological diseases.
3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7
Authors: Alam Sarfaraz , Khan Feroz 
Published: July 2017

AbstractGlobal prevalence of breast cancer and its rising frequency makes it a key area of research in drug discovery programs. The research article describes the development of field based 3D-QSAR model based on human breast cancer cell line MCF7 in vitro anticancer activity, which defines the molecular level understanding and regions of structure-activity relationship for triterpene maslinic acid and its analogs. The key features such as average shape, hydrophobic regions and electrostatic patterns of active compounds were mined and mapped to virtually screen potential analogs. Then, field points based descriptors were used to develop a 3D-QSAR model by aligning known active compounds onto identified pharmacophore template. The derived LOO validated PLS regression QSAR model showed acceptable r2 0.92 and q2 0.75. After screening through Lipinski’s rule of five filter for oral bioavailability, ADMET risk filter for drug like features, and synthetic accessibility for chemical synthesis, out of 593 hits, 39 were left top hits. Docking screening was performed through identified potential targets namely, AKR1B10, NR3C1, PTGS2, and HER2. Finally, compound P-902 was identified as best hit. This study, would be of great help in lead identification and optimization for early drug discovery.
Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence
Authors: Zhang Qiong , Nijampatnam Bhavitavya , Hua Zhang , Nguyen Thao , Zou Jing , Cai Xia , Michalek Suzanne M. , Velu Sadanandan E. , Wu Hui 
Published: July 2017

AbstractStreptococcus mutans employs a key virulence factor, three glucosyltransferase (GtfBCD) enzymes to establish cariogenic biofilms. Therefore, the inhibition of GtfBCD would provide anti-virulence therapeutics. Here a small molecule library of 500,000 small molecule compounds was screened in silico against the available crystal structure of the GtfC catalytic domain. Based on the predicted binding affinities and drug-like properties, small molecules were selected and evaluated for their ability to reduce S. mutans biofilms, as well as inhibit the activity of Gtfs. The most potent inhibitor was further characterized for Gtf binding using OctetRed instrument, which yielded low micromolar KD against GtfB and nanomolar KD against GtfC, demonstrating selectivity towards GtfC. Additionally, the lead compound did not affect the overall growth of S. mutans and commensal oral bacteria, and selectively inhibit the biofilm formation by S. mutans, indicative of its selectivity and non-bactericidal nature. The lead compound also effectively reduced cariogenicity in vivo in a rat model of dental caries. An analog that docked poorly in the GtfC catalytic domain failed to inhibit the activity of Gtfs and S. mutans biofilms, signifying the specificity of the lead compound. This report illustrates the validity and potential of structure-based design of anti-S. mutans virulence inhibitors.
Improved low-rank matrix recovery method for predicting miRNA-disease association
Authors: Peng Li , Peng Manman , Liao Bo , Huang Guohua , Liang Wei , Li Keqin 
Published: July 2017

AbstractMicroRNAs (miRNAs) performs crucial roles in various human diseases, but miRNA-related pathogenic mechanisms remain incompletely understood. Revealing the potential relationship between miRNAs and diseases is a critical problem in biomedical research. Considering limitation of existing computational approaches, we develop improved low-rank matrix recovery (ILRMR) for miRNA-disease association prediction. ILRMR is a global method that can simultaneously prioritize potential association for all diseases and does not require negative samples. ILRMR can also identify promising miRNAs for investigating diseases without any known related miRNA. By integrating miRNA-miRNA similarity information, disease-disease similarity information, and miRNA family information to matrix recovery, ILRMR performs better than other methods in cross validation and case studies.
Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI
Authors: Radinsky Olga , Edri Avishay , Brusilovsky Michael , Fedida-Metula Shlomit , Sobarzo Ariel , Gershoni-Yahalom Orly , Lutwama Julius , Dye John , Lobel Leslie , Porgador Angel 
Published: July 2017

AbstractEbolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors’ sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.
Comparative proteomic analysis of human embryonic stem cell-derived and primary human retinal pigment epithelium
Authors: Hongisto Heidi , Jylhä Antti , Nättinen Janika , Rieck Jochen , Ilmarinen Tanja , Veréb Zoltán , Aapola Ulla , Beuerman Roger , Petrovski Goran , Uusitalo Hannu , Skottman Heli 
Published: July 2017

AbstractHuman embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) provide an unlimited cell source for retinal cell replacement therapies. Clinical trials using hESC-RPE to treat diseases such as age-related macular degeneration (AMD) are currently underway. Human ESC-RPE cells have been thoroughly characterized at the gene level but their protein expression profile has not been studied at larger scale. In this study, proteomic analysis was used to compare hESC-RPE cells differentiated from two independent hESC lines, to primary human RPE (hRPE) using Isobaric tags for relative quantitation (iTRAQ). 1041 common proteins were present in both hESC-RPE cells and native hRPE with majority of the proteins similarly regulated. The hESC-RPE proteome reflected that of normal hRPE with a large number of metabolic, mitochondrial, cytoskeletal, and transport proteins expressed. No signs of increased stress, apoptosis, immune response, proliferation, or retinal degeneration related changes were noted in hESC-RPE, while important RPE specific proteins involved in key RPE functions such as visual cycle and phagocytosis, could be detected in the hESC-RPE. Overall, the results indicated that the proteome of the hESC-RPE cells closely resembled that of their native counterparts.