bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Highly Sensitive Biosensors of RAF Dimerization in Cells
Authors: Miyamoto Kyoko , Sawa Masaaki 
Published: January 2019

AbstractThe BRAF inhibitors dabrafenib and vemurafenib induce remarkable clinical responses in patients with BRAF-mutated melanomas. However, adverse events, including the emergence of secondary tumors and drug resistance, have been reported. Studies have revealed that undesirable RAF dimerization induced by inhibitors promotes these adverse effects. Here, we developed highly sensitive biosensors of RAF dimerization in cells utilizing the split enhanced click beetle luciferase (Emerald Luc, ELuc) complementation technique. We demonstrated that our biosensor system works effectively for high-throughput screens in the microplate format. A comprehensive analysis of commercially available RAF inhibitors performed using this assay system revealed that the inhibitors exhibit various potencies in inducing the dimerization of RAF isoforms, and their dimerization potencies do not always correlate with the RAF enzyme inhibition. This sensitive assay system will become a powerful tool to discover next-generation BRAF inhibitors with safer profiles.
Identification of Thermus aquaticus DNA polymerase variants with increased mismatch discrimination and reverse transcriptase activity from a smart enzyme mutant library
Authors: Raghunathan Govindan , Marx Andreas 
Published: January 2019

AbstractDNA polymerases the key enzymes for several biotechnological applications. Obviously, nature has not evolved these enzymes to be compatible with applications in biotechnology. Thus, engineering of a natural scaffold of DNA polymerases may lead to enzymes improved for several applications. Here, we investigated a two-step approach for the design and construction of a combinatorial library of mutants of KlenTaq DNA polymerase. First, we selected amino acid sites for saturation mutagenesis that interact with the primer/template strands or are evolutionarily conserved. From this library, we identified mutations that little interfere with DNA polymerase activity. Next, these functionally active mutants were combined randomly to construct a second library with enriched sequence diversity. We reasoned that the combination of mutants that have minuscule effect on enzyme activity and thermostability, will result in entities that have an increased mutation load but still retain activity. Besides activity and thermostability, we screened the library for entities with two distinct properties. Indeed, we identified two different KlenTaq DNA polymerase variants that either exhibit increased mismatch extension discrimination or increased reverse transcription PCR activity, respectively.
Close social relationships correlate with human gut microbiota composition
Authors: Dill-McFarland Kimberly A. , Tang Zheng-Zheng , Kemis Julia H. , Kerby Robert L. , Chen Guanhua , Palloni Alberto , Sorenson Thomas , Rey Federico E. , Herd Pamela 
Published: January 2019

AbstractSocial relationships shape human health and mortality via behavioral, psychosocial, and physiological mechanisms, including inflammatory and immune responses. Though not tested in human studies, recent primate studies indicate that the gut microbiome may also be a biological mechanism linking relationships to health. Integrating microbiota data into the 60-year-old Wisconsin Longitudinal Study, we found that socialness with family and friends is associated with differences in the human fecal microbiota. Analysis of spouse (N = 94) and sibling pairs (N = 83) further revealed that spouses have more similar microbiota and more bacterial taxa in common than siblings, with no observed differences between sibling and unrelated pairs. These differences held even after accounting for dietary factors. The differences between unrelated individuals and married couples was driven entirely by couples who reported close relationships; there were no differences in similarity between couples reporting somewhat close relationships and unrelated individuals. Moreover, married individuals harbor microbial communities of greater diversity and richness relative to those living alone, with the greatest diversity among couples reporting close relationships, which is notable given decades of research documenting the health benefits of marriage. These results suggest that human interactions, especially sustained, close marital relationships, influence the gut microbiota.
Role of ceramide synthase 2 in G-CSF signaling and G-CSF-R translocation into detergent-resistant membranes
Authors: Kurz Jennifer , Barthelmes Julia , Blum Leonard , Ulshöfer Thomas , Wegner Marthe-Susanna , Ferreirós Nerea , Roser Luise , Geisslinger Gerd , Grösch Sabine , Schiffmann Susanne 
Published: January 2019

AbstractCeramides are sphingolipids with defined acyl chain lengths, which are produced by corresponding ceramide synthases (CerS1-6). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), the ablation of CerS2 suppresses EAE-pathology by reducing neutrophil migration into the central nervous system. This migration is induced by granulocyte-colony stimulating factor (G-CSF) signaling. G-CSF signaling leads to a signal cascade including the phosphorylation of Lyn kinase and STAT3. This in turn regulates expression of the neutrophil surface receptor chemokine receptor 2 (CXCR2) and causes translocation of the receptor into detergent-resistant membranes (DRMs). In this study we investigated the role of ceramides in G-CSF signaling. We found, that G-CSF treatment of wild type bone marrow cells (BMCs) leads to translocation of G-CSF-receptor (G-CSF-R) into DRMs. G-CSF also induces downregulation of ceramides in WT and CerS2 null BMCs, as well as upregulation of very long chain lactosylceramides. However, in CerS2 null BMCs, G-CSF failed to induce translocation of G-CSF-R into DRMs, leading to reduced phosphorylation of Lyn and reduced CXCR2 expression. Interestingly, G-CSF signaling in CerS6 null BMCs was not affected. In conclusion, very long chain ceramides are important for G-CSF signaling and translocation of G-CSF-R into DRMs.
Impact of short-term extreme temperature events on physiological performance of Salicornia ramosissima J. Woods under optimal and sub-optimal saline conditions
Authors: Pérez-Romero Jesús Alberto , Barcia-Piedras Jose-Maria , Redondo-Gómez Susana , Mateos-Naranjo Enrique 
Published: January 2019

AbstractIncreasing extreme temperature climatic events could exert an important effect on plant photosynthetic performance, which could be modulated by the co-occurrence with other environmental factors, such as salinity, in estuarine ecosystems. Therefore, a mesocosm experiment was designed to assess the impact of temperature events for three days (13/5 °C, 25/13 °C and 40/28 °C) in combination with two NaCl concentrations (171 and 1050 mM NaCl) on the physiological performance of Salicornia ramosissima. Extreme temperature events had a negative impact on S. ramosissima photosynthetic efficiency, this effect being more marked with cold wave at both salinities, compared with heat wave, even in presence of NaCl excess. This differential thermotolerance in the photosynthetic apparatus was ascribed to the greater integrity and functioning of its photosynthetic pathway at high temperature, as indicated by constant gs,Vc,max values at optimal salinity and the higher values of those parameters and gm recorded in combination with NaCl excess. Moreover, S. ramosissima was able to upregulate the energy sink capacity of its photochemical apparatus at elevated temperature and salinity by a greater energy excess dissipation capacity. This could have contributed to reducing the risk of oxidative stress, along with the recorded higher capacity for antioxidant enzyme activity modulation under these conditions.
Separate multisensory integration processes for ownership and localization of body parts
Authors: Matsumiya Kazumichi 
Published: January 2019

AbstractThe experiences that body parts are owned and localized in space are two key aspects of body awareness. Although initial work assumed that the perceived location of one’s body part can be used as a behavioral measure to assess the feeling of owning a body part, recent studies call into question the relationship between localization and ownership of body parts. Yet, little is known about the processes underlying these two aspects of body-part awareness. Here, I applied a statistically optimal cue combination paradigm to a perceptual illusion in which ownership over an artificial hand is experienced, and found that variances predicted by a model of optimal cue combination are similar to those observed in localization of the participant’s hand, but systematically diverge from those observed in ownership of the artificial hand. These findings provide strong evidence for separate processes between ownership and localization of body parts, and indicate a need to revise current models of body part ownership. Results from this study suggest that the neural substrates for perceptual identification of one’s body parts—such as body ownership—are distinct from those underlying spatial localization of the body parts, thus implying a functional distinction between “who” and “where” in the processing of body part information.
Virulence Characteristics and an Action Mode of Antibiotic Resistance in Multidrug-Resistant Pseudomonas aeruginosa
Authors: Hwang Wontae , Yoon Sang Sun 
Published: January 2019

AbstractPseudomonas aeruginosa displays intrinsic resistance to many antibiotics and known to acquire actively genetic mutations for further resistance. In this study, we attempted to understand genomic and transcriptomic landscapes of P. aeruginosa clinical isolates that are highly resistant to multiple antibiotics. We also aimed to reveal a mode of antibiotic resistance by elucidating transcriptional response of genes conferring antibiotic resistance. To this end, we sequenced the whole genomes and profiled genome-wide RNA transcripts of three different multi-drug resistant (MDR) clinical isolates that are phylogenetically distant from one another. Multi-layered genome comparisons with genomes of antibiotic-susceptible P. aeruginosa strains and 70 other antibiotic-resistance strains revealed both well-characterized conserved gene mutations and distinct distribution of antibiotic-resistant genes (ARGs) among strains. Transcriptions of genes involved in quorum sensing and type VI secretion systems were invariably downregulated in the MDR strains. Virulence-associated phenotypes were further examined and results indicate that our MDR strains are clearly avirulent. Transcriptions of 64 genes, logically selected to be related with antibiotic resistance in MDR strains, were active under normal growth conditions and remained unchanged during antibiotic treatment. These results propose that antibiotic resistance is achieved by a “constitutive” response scheme, where ARGs are actively expressed even in the absence of antibiotic stress, rather than a “reactive” response. Bacterial responses explored at the transcriptomic level in conjunction with their genome repertoires provided novel insights into (i) the virulence-associated phenotypes and (ii) a mode of antibiotic resistance in MDR P. aeruginosa strains.
The association between intraoperative urine output and postoperative acute kidney injury differs between partial and radical nephrectomy
Authors: Hur Min , Park Sun-Kyung , Yoo Seokha , Choi Sheung-Nyoung , Jeong Chang Wook , Kim Won Ho , Kim Jin-Tae , Kwak Cheol , Bahk Jae-Hyon 
Published: January 2019

AbstractWe sought to investigate the association between intraoperative urine output and postoperative acute kidney injury (AKI) in patients undergoing radical and partial nephrectomy. We retrospectively reviewed data of 742 patients. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. The relationship between intraoperative urine output and the risk of AKI was evaluated by multivariable logistic regression analysis in radical and partial nephrectomy, separately. Minimum P-value approach was used to find the optimal threshold of intraoperative oliguria associated with the risk of AKI. The incidence of AKI was 14.4% (67/466) after partial nephrectomy and 57.6% (159/276) after radical nephrectomy. For partial nephrectomy, multivariable analysis showed that renal ischemic time, operation time, open surgery and intraoperative transfusion were significantly associated with AKI. For radical nephrectomy, history of hypertension, baseline glomerular filtration rate and intraoperative mean urine output were significantly associated with AKI. Intraoperative mean urine output during radical nephrectomy was associated with AKI after radical nephrectomy, while not after partial nephrectomy. Mean urine output <1.0 mL/kg/h was determined to be an optimal cutoff of AKI after radical nephrectomy. Intraoperative oliguria may have different clinical implication for AKI between partial and radical nephrectomy.
Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)
Authors: Espín-Pérez Almudena , Hebels Dennie G. A. J. , Kiviranta Hannu , Rantakokko Panu , Georgiadis Panagiotis , Botsivali Maria , Bergdahl Ingvar A. , Palli Domenico , Späth Florentin , Johansson Anders , Chadeau-Hyam Marc , Kyrtopoulos Soterios A. , Kleinjans Jos C. S. , de Kok Theo M. C. M. 
Published: January 2019

AbstractPCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.
Determination of Ultrastructural Properties of Human Carotid Atherosclerotic Plaques by Scanning Acoustic Microscopy, Micro-Computer Tomography, Scanning Electron Microscopy and Energy Dispersive X-Ray Spectroscopy
Authors: Bilen Bukem , Sener Leyla Turker , Albeniz Isil , Sezen Meltem , Unlu Mehmet Burcin , Ugurlucan Murat 
Published: January 2019

AbstractMicrocalcification is the precursor of vulnerability of plaques in humans. Visualization of such small structures in vivo with high spatial resolution is an unsolved issue. The goal of this study is to evaluate the potential of scanning acoustic microscopy (SAM) in the determination of atherosclerotic plaques with calcifications by validating this technique with micro-computer tomography (micro-CT), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The fibrocalcific plaques were obtained from 12 different patients and initially examined with micro-CT. The images exhibited calcifications within these plaques. For imaging with SAM, approximately 5 μm thick slices were prepared. Sound speed values within calcified regions were measured to be greater than the ones in collagen-rich regions. These fibrocalcific plaques were also examined with SEM and EDS revealing collagen and calcium deposition within these samples. The consistency of the results obtained by all of the modalities involved in our study is an indication of the potential of SAM as a clinical tool for the diagnosis of vulnerable plaques.
How Quantum Mechanics can consistently describe the use of itself
Authors: Lazarovici Dustin , Hubert Mario 
Published: January 2019

AbstractWe discuss the no-go theorem of Frauchiger and Renner based on an “extended Wigner’s friend” thought experiment which is supposed to show that any single-world interpretation of quantum mechanics leads to inconsistent predictions if it is applicable on all scales. We show that no such inconsistency occurs if one considers a complete description of the physical situation. We then discuss implications of the thought experiment that have not been clearly addressed in the original paper, including a tension between relativity and nonlocal effects predicted by quantum mechanics. Our discussion applies in particular to Bohmian mechanics.
Toxicity of diatom-derived polyunsaturated aldehyde mixtures on sea urchin Paracentrotus lividus development
Authors: Ruocco Nadia , Annunziata Concetta , Ianora Adrianna , Libralato Giovanni , Manfra Loredana , Costantini Susan , Costantini Maria 
Published: January 2019

AbstractDiatom-derived polyunsaturated aldehydes (PUAs), decadienal, heptadienal and octadienal, derive from the oxidation of fatty acids and have cytotoxic and anticancer effects. PUAs, tested separately, induce malformations in sea urchin Paracentrotus lividus embryos. Decadienal induces the worst malformations and lowest survival rates. Interestingly, decadienal, heptadienal and octadienal place in motion several genes to counteract their negative effects. To date, no studies are available reporting on the effects of PUA mixtures on marine invertebrates. Here we test binary and ternary mixtures on embryonic development of P. lividus. Our findings demonstrate that mixtures of PUAs act (i) at morphological level in synergistic way, being much more severe compared to individual PUAs; (ii) at molecular level also reveal an additive effect, affecting almost all fifty genes, previously tested using individual PUAs. This study is relevant from an ecological point of view since diatoms are a major food source for both pelagic and benthic organisms. This work opens new perspectives for understanding the molecular mechanisms that marine organisms use in reacting to environmental natural toxin mixtures such as diatom PUAs.
Sonic hedgehog signaling is negatively regulated in reactive astrocytes after forebrain stab injury
Authors: Allahyari R. Vivian , Clark K. Lyles , Shepard Katherine A. , Garcia A. Denise R. 
Published: January 2019

AbstractFollowing injury to the central nervous system, astrocytes perform critical and complex functions that both promote and antagonize neural repair. Understanding the molecular signaling pathways that coordinate their diverse functional properties is key to developing effective therapeutic strategies. In the healthy, adult CNS, Sonic hedgehog (Shh) signaling is active in mature, differentiated astrocytes. Shh has been shown to undergo injury-induced upregulation and promote neural repair. Here, we investigated whether Shh signaling mediates astrocyte response to injury. Surprisingly, we found that following an acute, focal injury, reactive astrocytes exhibit a pronounced reduction in Shh activity in a spatiotemporally-defined manner. Shh signaling is lost in reactive astrocytes at the lesion site, but persists in mild to moderately reactive astrocytes in distal tissues. Nevertheless, local pharmacological activation of the Shh pathway in astrocytes mitigates inflammation, consistent with a neuroprotective role for Shh signaling after injury. Interestingly, we find that Shh signaling is restored to baseline levels two weeks after injury, a time during which acute inflammation has largely subsided and lesions have matured. Taken together, these data suggest that endogenous Shh signaling in astrocytes is dynamically regulated in a context dependent manner. In addition, exogenous activation of the Shh pathway promotes neuroprotection mediated by reactive astrocytes.
Paenibacillus polymyxa biofilm polysaccharides antagonise Fusarium graminearum
Authors: Timmusk Salme , Copolovici Dana , Copolovici Lucian , Teder Tiiu , Nevo Eviatar , Behers Lawrence 
Published: January 2019

AbstractFusarium Head Blight (FHB) caused by Fusarium graminearum pathogens constitutes a major threat to agricultural production because it frequently reduces the yield and quality of the crop. The disease severity is predicted to increase in various regions owing to climate change. Integrated management where biocontrol plays an important role has been suggested in order to fight FHB. P. polymyxa A26 is known to be an effective antagonist against F. graminearum. Deeper understanding of the mode of action of P. polymyxa A26 is needed to develop strategies for its application under natural settings in order to effectively overcome the pathogenic effects. This study aims to re-evaluate a former study and reveal whether compounds other than non-ribosomal antibiotic lipopeptides could be responsible for the antagonistic effect, despite what is often reported. Wheat seedlings were grown to maturity and the spikes infected with the pathogen under greenhouse conditions. The development of FHB infection, quantified via the disease incidence severity and 100-kernel weight, was strongly correlated (r > 0.78, p < 0.01) with the content of the polysaccharide component D-glucuronic acid in the biofilm. Furthermore, while increased inoculum density from 106 to 108 cells/ml did not affect wild type performance, a significant increase was observed with the P. polymyxa mutant deficient in nonribosomal lipopeptide synthesis. Our results show that P. polymyxa A26 biofilm extracellular polysaccharides are capable of antagonizing F. graminearum and that the uronate content of the polysaccharides is of critical importance in the antagonism.
Complementary Proteomics, Genomics approaches identifies potential pathogenicity/virulence factors in Tilletia indica induced under the influence of host factor
Authors: Pandey Vishakha , Gupta Atul Kumar , Singh Manoj , Pandey Dinesh , Kumar Anil 
Published: January 2019

AbstractKarnal bunt disease of wheat is incited by quarantine fungal pathogenT.indica. Till date, there is little information on the pathogenic mechanisms involved in Karnal bunt. In order to understand the molecular mechanisms of disease pathogenesis, highly aggressiveT.indicaTiK isolate was cultured in the presence of host factor extracted from developing spikes of wheat variety WH-542. Modulation in protein profile of mycelial proteins and secretome from TiK cultured in the absence and presence of host factor was analyzed by 2-DE. Fifteen and twenty nine protein spots were up-regulated/differentially regulated in the proteome of mycelial and secreted proteins, respectively and identified using MALDI-TOF/TOF. Identified proteins are involved in suppression of host defense responses, lignin degradation of plant cell wall, penetration, adhesion of pathogen to host tissues, pathogen mediated reactive oxygen species generation, hydrolytic enzymes, detoxification of host generated reactive oxygen species. Further, integration of proteomic and genomic analysis has led to candidate pathogenicity/virulence factors identification. They were functionally annotated by sequence as well as structure based analysis. In this study, complementation of proteomics and genomics approaches resulted in novel pathogenicity/virulence factor(s) identification inT.indica.