bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular insights into antibiotic resistance - how a binding protein traps albicidin
Authors: Rostock Lida , Driller Ronja , Grätz Stefan , Kerwat Dennis , von Eckardstein Leonard , Petras Daniel , Kunert Maria , Alings Claudia , Schmitt Franz-Josef , Friedrich Thomas , Wahl Markus C. , Loll Bernhard , Mainz Andi , Süssmuth Roderich D. 
Published: July 2018

AbstractThe worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs.
Synthetic microbe communities provide internal reference standards for metagenome sequencing and analysis
Authors: Hardwick Simon A. , Chen Wendy Y. , Wong Ted , Kanakamedala Bindu S. , Deveson Ira W. , Ongley Sarah E. , Santini Nadia S. , Marcellin Esteban , Smith Martin A. , Nielsen Lars K. , Lovelock Catherine E. , Neilan Brett A. , Mercer Tim R. 
Published: July 2018

AbstractThe complexity of microbial communities, combined with technical biases in next-generation sequencing, pose a challenge to metagenomic analysis. Here, we develop a set of internal DNA standards, termed “sequins” (sequencing spike-ins), that together constitute a synthetic community of artificial microbial genomes. Sequins are added to environmental DNA samples prior to library preparation, and undergo concurrent sequencing with the accompanying sample. We validate the performance of sequins by comparison to mock microbial communities, and demonstrate their use in the analysis of real metagenome samples. We show how sequins can be used to measure fold change differences in the size and structure of accompanying microbial communities, and perform quantitative normalization between samples. We further illustrate how sequins can be used to benchmark and optimize new methods, including nanopore long-read sequencing technology. We provide metagenome sequins, along with associated data sets, protocols, and an accompanying software toolkit, as reference standards to aid in metagenomic studies.
An atmospheric chronology for the glacial-deglacial Eastern Equatorial Pacific
Authors: Zhao Ning , Keigwin Lloyd D. 
Published: July 2018

AbstractPaleoclimate reconstructions are only as good as their chronology. In particular, different chronological assumptions for marine sediment cores can lead to different reconstructions of ocean ventilation age and atmosphere−ocean carbon exchange history. Here we build the first high-resolution chronology that is free of the dating uncertainties common in marine sediment records, based on radiocarbon dating twigs found with computed tomography scans in two cores from the Eastern Equatorial Pacific (EEP). With this accurate chronology, we show that the ventilation ages of the EEP thermocline and intermediate waters were similar to today during the Last Glacial Maximum and deglaciation, in contradiction with previous studies. Our results suggest that the glacial respired carbon pool in the EEP was not significantly older than today, and that the deglacial strengthening of the equatorial Pacific carbon source was probably driven by low-latitude processes rather than an increased subsurface supply of upwelled carbon from high-latitude oceans.
NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer
Authors: Ludlow Andrew T. , Wong Mandy Sze , Robin Jerome D. , Batten Kimberly , Yuan Laura , Lai Tsung-Po , Dahlson Nicole , Zhang Lu , Mender Ilgen , Tedone Enzo , Sayed Mohammed E. , Wright Woodring E. , Shay Jerry W. 
Published: July 2018

AbstractAlternative splicing is dysregulated in cancer and the reactivation of telomerase involves the splicing of TERT transcripts to produce full-length (FL) TERT. Knowledge about the splicing factors that enhance or silence FL hTERT is lacking. We identified splicing factors that reduced telomerase activity and shortened telomeres using a siRNA minigene reporter screen and a lung cancer cell bioinformatics approach. A lead candidate, NOVA1, when knocked down resulted in a shift in hTERT splicing to non-catalytic isoforms, reduced telomerase activity, and progressive telomere shortening. NOVA1 knockdown also significantly altered cancer cell growth in vitro and in xenografts. Genome engineering experiments reveal that NOVA1 promotes the inclusion of exons in the reverse transcriptase domain of hTERT resulting in the production of FL hTERT transcripts. Utilizing hTERT splicing as a model splicing event in cancer may provide new insights into potentially targetable dysregulated splicing factors in cancer.
Breast cancer diagnosed during pregnancy is associated with enrichment of non-silent mutations, mismatch repair deficiency signature and mucin mutations
Authors: Nguyen Bastien , Venet David , Azim Hatem A. , Brown David , Desmedt Christine , Lambertini Matteo , Majjaj Samira , Pruneri Giancarlo , Peccatori Fedro , Piccart Martine , Rothé Françoise , Sotiriou Christos 
Published: July 2018

AbstractBreast cancer diagnosed during pregnancy (BCP) is a rare and highly challenging disease. To investigate the impact of pregnancy on the biology of breast cancer, we conducted a comparative analysis of a cohort of BCP patients and non-pregnant control patients by integrating gene expression, copy number alterations and whole genome sequencing data. We showed that BCP exhibit unique molecular characteristics including an enrichment of non-silent mutations, a higher frequency of mutations in mucin gene family and an enrichment of mismatch repair deficiency mutational signature. This provides important insights into the biology of BCP and suggests that these features may be implicated in promoting tumor progression during pregnancy. In addition, it provides an unprecedented resource for further understanding the biology of breast cancer in young women and how pregnancy could modulate tumor biology.
Unsupervised phase mapping of X-ray diffraction data by nonnegative matrix factorization integrated with custom clustering
Authors: Stanev Valentin , Vesselinov Velimir V. , Kusne A. Gilad , Antoszewski Graham , Takeuchi Ichiro , Alexandrov Boian S. 
Published: July 2018

AbstractAnalyzing large X-ray diffraction (XRD) datasets is a key step in high-throughput mapping of the compositional phase diagrams of combinatorial materials libraries. Optimizing and automating this task can help accelerate the process of discovery of materials with novel and desirable properties. Here, we report a new method for pattern analysis and phase extraction of XRD datasets. The method expands the Nonnegative Matrix Factorization method, which has been used previously to analyze such datasets, by combining it with custom clustering and cross-correlation algorithms. This new method is capable of robust determination of the number of basis patterns present in the data which, in turn, enables straightforward identification of any possible peak-shifted patterns. Peak-shifting arises due to continuous change in the lattice constants as a function of composition and is ubiquitous in XRD datasets from composition spread libraries. Successful identification of the peak-shifted patterns allows proper quantification and classification of the basis XRD patterns, which is necessary in order to decipher the contribution of each unique single-phase structure to the multi-phase regions. The process can be utilized to determine accurately the compositional phase diagram of a system under study. The presented method is applied to one synthetic and one experimental dataset and demonstrates robust accuracy and identification abilities.
Study on the Aging Mechanism of Boron Potassium Nitrate (BKNO3) for Sustainable Efficiency in Pyrotechnic Mechanical Devices
Authors: Lee Junwoo , Kim Taewan , Ryu Seung Un , Choi Kyoungwon , Ahn Gil Hwan , Paik Jong Gyu , Ryu Byungtae , Park Taiho , Won Yong Sun 
Published: July 2018

AbstractThe aging of propellants in PMDs is considered to be one of the primary factors affecting the performance of PMDs. Thus, studies on the aging mechanism of propellants, which have not yet been addressed extensively, pose a solution to securing the sustainable operation of PMDs. We characterized one of the most commonly used commercial propellants (boron potassium nitrate (BKNO3)) and investigated its aging mechanism rigorously. Based on thermal analyses, we demonstrate that the decomposition of laminac, a polymer binder, is the fastest spontaneous reaction. However, it will not self-initiate at a storage temperature as high as 120 °C. The effect of the humidity level was examined by characterizing BKNO3 samples prepared. The heat of reaction and the reaction rate decreased by 18% and 67% over 16 weeks of aging, respectively. This is attributed to the oxide shells on the surface of boron particles. The formation of oxide shells could be confirmed using X-ray photoelectron spectroscopy and transmission electron microscopy–energy dispersive spectroscopy. In conclusion, surface oxide formation with the aging of BKNO3 will decrease its propulsive efficiency; oxidation reduces the potential energy of the system and the resulting oxide decreases the reaction rate.
Enhanced Defluoridation Using Novel Millisphere Nanocomposite of La-Doped Li-Al Layered Double Hydroxides Supported by Polymeric Anion Exchanger
Authors: Cai Jianguo , Zhang Yanyang , Qian Yue , Shan Chao , Pan Bingcai 
Published: July 2018

AbstractA novel nanocomposite bead LaLiAl-LDH@201 was fabricated by doping a small amount of La into nanocrystalline Li/Al layered double hydroxides (LDHs) pre-confined inside polystyrene anion exchanger D201 (LiAl-LDH@201). A systematic characterisation of the resultant LaLiAl-LDH@201 (XRD, SEM-EDS, TEM-EDS, and XPS) evidenced the successful incorporation of La into the Li/Al LDHs, with their interlayer distance expanded to allow more exchangeable sites for fluoride uptake. The resultant LaLiAl-LDH@201 showed high and stable defluoridation performance over a wide range of pH from 4 to 9. The superior uptake capacity and affinity for fluoride of LaLiAl-LDH@201 over LiAl-LDH@201 were driven by both the increased anion exchange capacity of the embedded LDHs and the specific La-F interaction evidenced via XPS and TEM-EDS characterisation. Fixed-bed column test confirmed that the working capacity of LaLiAl-LDH@201 for defluoridation of authentic fluoride-rich groundwater was nearly twice that of LiAl-LDH@201. The fluoride-loaded LaLiAl-LDH@201 could be conveniently regenerated in situ by using NaOH + NaCl binary solution, achieving desorption efficiency above 98%. Moreover, negligible capacity loss, La leaching, or structure alteration was observed after five adsorption-regeneration cycles, indicating the high stability of LaLiAl-LDH@201. Therefore, the novel millisphere nanocomposite LaLiAl-LDH@201 was promising for efficient defluoridation from water and wastewater.
Confronting species aesthetics with ecological functions in coral reef fish
Authors: Tribot Anne-Sophie , Carabeux Quentin , Deter Julie , Claverie Thomas , Villéger Sébastien , Mouquet Nicolas 
Published: July 2018

AbstractThe biodiversity crisis has spurred scientists to assess all facets of biodiversity so that stakeholders can establish protection programs. However, species that are perceived as beautiful receive more attention than less attractive species. This dynamic could have tremendous consequences on people’s willingness to preserve biodiversity. Coral reefs might be particularly affected by this issue as they are key ecosystems that provide many services, such as aesthetic and cultural benefits attracting millions of tourists each year. Here we show the results of an online photographic questionnaire completed by 8,000 participants whereby preferences were assessed for a set of 116 reef fishes. Based on these preferences, we compared the functional richness, i.e. the amount of functional space filled, by groups of fishes based on their perceived attractiveness. We present evidence indicating that the least attractive coral reef fishes have a much higher functional richness than the most attractive species. Our results highlight the extent to which species aesthetic values’ may be disconnected from their ecological values and could be misleading for conservation purposes. There is thus an urgent need to increase the attention of scientists and the general public towards less attractive species to better appreciate and protect the species that crucially support functional diversity in endangered ecosystems.
Development of an inducible anti-VEGF rAAV gene therapy strategy for the treatment of wet AMD
Authors: Reid Christopher A. , Nettesheim Emily R. , Connor Thomas B. , Lipinski Daniel M. 
Published: July 2018

AbstractVascular endothelial growth factor (VEGF) is a key mediator in the development and progression of choroidal neovascularization (CNV) in patients with wet age-related macular degeneration (AMD). As a consequence, current treatment strategies typically focus on the administration of anti-VEGF agents, such as Aflibercept (Eylea), that inhibit VEGF function. While this approach is largely successful at counteracting CNV progression, the treatment can require repetitive (i.e. monthly) intravitreal injections of the anti-VEGF agent throughout the patient’s lifetime, imposing a substantial financial and medical burden on the patient. Moreover, repetitive injection of anti-VEGF agents over a period of years may encourage progression of retinal and choroidal atrophy in patients with AMD, leading to a decrease in visual acuity. Herein, we have developed a single-injection recombinant adeno-associated virus (rAAV)-based gene therapy treatment for wet AMD that prevents CNV formation through inducible over-expression of Eylea. First, we demonstrate that by incorporating riboswitch elements into the rAAV expression cassette allows protein expression levels to be modulated in vivo through oral supplementation on an activating ligand (e.g. tetracycline). We subsequently utilized this technology to modulate the intraocular concentration of Eylea following rAAV delivery, leading to nearly complete (p = 0.0008) inhibition of clinically significant CNV lesions in an established mouse model of wet AMD. The results shown in this study pave the way for the development of a personalized gene therapy strategy for the treatment of wet AMD that is substantially less invasive and more clinically adaptable than the current treatment paradigm of repetitive bolus injections of anti-VEGF agents.
Spatial segregation of home ranges between neighbouring colonies in a diurnal raptor
Authors: Cecere Jacopo G. , Bondì Salvatore , Podofillini Stefano , Imperio Simona , Griggio Matteo , Fulco Egidio , Curcio Andrea , Ménard Delphine , Mellone Ugo , Saino Nicola , Serra Lorenzo , Sarà Maurizio , Rubolini Diego 
Published: July 2018

AbstractEnhancement of information transfer has been proposed as a key driver of the evolution of coloniality. Transfer of information on location of food resources implies that individuals from the same colony share foraging areas and that each colony can be associated to a specific foraging area. In colonial breeding vertebrates, colony-specific foraging areas are often spatially segregated, mitigating intercolony intraspecific competition. By means of simultaneous GPS tracking of lesser kestrels (Falco naumanni) from neighbouring colonies, we showed a clear segregation of space use between individuals from different colonies. Foraging birds from different neighbouring colonies had home ranges that were significantly more segregated in space than expected by chance. This was the case both between large and between small neighbouring colonies. To our knowledge, the lesser kestrel is the only terrestrial species where evidence of spatial segregation of home ranges between conspecifics from neighbouring colonies has been demonstrated. The observed spatial segregation pattern is consistent with the occurrence of public information transfer about foraging areas and with the avoidance of overexploited areas located between neighbouring colonies. Our findings support the idea that spatial segregation of exploited areas may be widespread among colonial avian taxa, irrespective of colony size.
Tigecycline as a dual inhibitor of retinoblastoma and angiogenesis via inducing mitochondrial dysfunctions and oxidative damage
Authors: Xiong Ying , Liu Wei , Huang Qian , Wang Jierong , Wang Yanjun , Li Huijuan , Fu Xuedong 
Published: July 2018

AbstractRetinoblastoma is the most common intraocular malignancy in children with poor prognosis. The progression of retinoblastoma is dependent on a robust angiogenic response. Targeting both retinoblastoma cells and angiogenesis may therefore provide an alternative therapeutic strategy in retinoblastoma. Here, we demonstrated the inhibitory effects of tigecycline, a FDA-approved antibiotic, in retinoblastoma and angiogenesis in vitro and in vivo. We showed that tigecycline significantly inhibited growth and induced caspase-dependent apoptosis of multiple retinoblastoma cell lines. Tigecycline also effectively inhibited angiogenesis through suppressing capillary network formation, migration, proliferation and survival of human retinal microvascular endothelial cell (HREC). Mechanistically, tigecycline acts on both retinoblastoma cells and HREC via inhibiting mitochondrial protein translation, resulting in mitochondrial dysfunction, energy crisis, and oxidative damage. Importantly, we demonstrated the in vivo efficacy of tigecycline in inhibiting retinoblastoma and angiogenesis, and inducing oxidative stress on xenograft mouse model. In addition, ATP levels and growth rates were largely affected in retinoblastoma ρ0 cells that lacked mitochondrial respiration. Our work provides systematic pre-clinical evidence for repurposing tigecycline from its traditional use for retinoblastoma treatment. Our work demonstrates the essential roles of mitochondrial metabolism in both retinoblastoma and its angiogenesis.
Estimation of the cancer risk induced by therapies targeting stem cell replication and treatment recommendations
Authors: Meyer-Hermann Michael 
Published: July 2018

AbstractRejuvenation of stem cell activity might increase life expectancy by prolonging functionality of organs. Higher stem cell replication rates also bear the risk of cancer. The extent of this risk is not known. While it is difficult to evaluate this cancer risk in experiments, it can be estimated using a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model recapitulates the observation that treatments targeting stem cell replication can induce a substantial delay of organ failure. The model predicts that the cancer risk is minor under particular conditions. It depends on the assumed implications for cell damage repair during treatment. The benefit of rejuvenation therapy and its impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of systemic treatments. In recent years, the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. In this context, the model predicts that the treatment schedule is critical for success and that schedules successful in animal experiments are not transferable to humans. Guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of stem cell rejuvenation treatment protocols and the identification of critical parameters for cancer risk.
Developmental auditory exposure shapes responses of catecholaminergic neurons to socially-modulated song
Authors: Barr Helena J. , Woolley Sarah C. 
Published: July 2018

AbstractDevelopmental sensory experience is critical to the tuning of sensory systems and can shape perceptual abilities and their neural substrates. Neuromodulators, including catecholamines, contribute to sensory plasticity in both older and younger individuals and provide a mechanism for translating sensory experience into changes in brain and behavior. Less well known, however, is whether developmental sensory experience has lasting effects on the neuromodulatory neurons themselves. Here, we used female zebra finches to investigate the degree to which developmental auditory experience can have lasting effects on the density and sensory responsiveness of catecholamine-synthesizing neuron populations. We found that hearing courtship, but not non-courtship, song increased expression of the activity-dependent immediate early gene cFOS in dopamine neurons of the caudal ventral tegmental area (VTA) and this increase was dependent on whether females heard adult song during development. Developmental song exposure also affected the density of dopamine producing neurons in the rostral VTA. In contrast, song-evoked responses in noradrenergic neurons of the Locus Coeruleus were not affected by either developmental song exposure or the social context of the stimulus. These data highlight the lasting effects that developmental auditory experience can have in shaping both the density and sensory responsiveness of dopamine neuron populations.
PLVAP and GKN3 Are Two Critical Host Cell Receptors Which Facilitate Japanese Encephalitis Virus Entry Into Neurons
Authors: Mukherjee Sriparna , Sengupta Nabonita , Chaudhuri Ankur , Akbar Irshad , Singh Noopur , Chakraborty Sibani , Suryawanshi Amol Ratnakar , Bhattacharyya Arindam , Basu Anirban 
Published: July 2018

AbstractJapanese Encephalitis Virus (JEV), a globally important pathogen, belongs to the family Flaviviridae, is transmitted between vertebrate hosts by mosquitoes, principally by Culex tritaeniorhynchus. The E-glycoprotein of the virus mediates its attachment to the host cell receptors. In this study, we cloned and purified JEV E-glycoprotein in pET28a vector using E. coli BL21 (DE3) cells. A pull down assay was performed using plasma membrane fraction of BALB/c mouse brain and E-glycoprotein as a bait protein. 2-Dimensional Gel Electrophoresis based separation of the interacting proteins was analyzed by mass spectrometry. Among all the identified partners of E-glycoprotein, PLVAP (Plasmalemma vesicle associated protein) and GKN3 (Gastrokine3) showed significant up-regulation in both JEV infected mouse brain and neuro2a cells. In-silico studies also predicted significant interaction of these receptors with E-glycoprotein. Additionally, overexperssion and silencing of these receptors resulted in increase and reduction in viral load respectively, suggesting them as two critical cellular receptors governing JEV entry and propagation in neurons. In support, we observed significant expression of PLVAP but not GKN3 in post-mortem autopsied human brain tissue. Our results establish two novel receptor proteins in neurons in case of JEV infection, thus providing potential targets for antiviral research.