bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus
Authors: Owen C. David , Tailford Louise E. , Monaco Serena , Šuligoj Tanja , Vaux Laura , Lallement Romane , Khedri Zahra , Yu Hai , Lecointe Karine , Walshaw John , Tribolo Sandra , Horrex Marc , Bell Andrew , Chen Xi , Taylor Gary L. , Varki Ajit , Angulo Jesus , Juge Nathalie 
Published: December 2017

AbstractRuminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut.
Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer
Authors: Liu David , Abbosh Philip , Keliher Daniel , Reardon Brendan , Miao Diana , Mouw Kent , Weiner-Taylor Amaro , Wankowicz Stephanie , Han Garam , Teo Min Yuen , Cipolla Catharine , Kim Jaegil , Iyer Gopa , Al-Ahmadie Hikmat , Dulaimi Essel , Chen David Y. T. , Alpaugh R. Katherine , Hoffman-Censits Jean , Garraway Levi A. , Getz Gad , Carter Scott L. , Bellmunt Joaquim , Plimack Elizabeth R. , Rosenberg Jonathan E. , Van Allen Eliezer M. 
Published: December 2017

AbstractDespite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts worse overall survival, and further observe alterations in cell-cycle and immune checkpoint regulation genes in post-treatment tumors. These results provide insight into the clinical and genomic dynamics of tumor evolution with cisplatin-based chemotherapy, suggest mechanisms of clinical resistance, and inform development of clinically relevant biomarkers and trials of combination therapies.
Generalized laws of thermodynamics in the presence of correlations
Authors: Bera Manabendra N. , Riera Arnau , Lewenstein Maciej , Winter Andreas 
Published: December 2017

AbstractThe laws of thermodynamics, despite their wide range of applicability, are known to break down when systems are correlated with their environments. Here we generalize thermodynamics to physical scenarios which allow presence of correlations, including those where strong correlations are present. We exploit the connection between information and physics, and introduce a consistent redefinition of heat dissipation by systematically accounting for the information flow from system to bath in terms of the conditional entropy. As a consequence, the formula for the Helmholtz free energy is accordingly modified. Such a remedy not only fixes the apparent violations of Landauer’s erasure principle and the second law due to anomalous heat flows, but also leads to a generally valid reformulation of the laws of thermodynamics. In this information-theoretic approach, correlations between system and environment store work potential. Thus, in this view, the apparent anomalous heat flows are the refrigeration processes driven by such potentials.
Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington’s Disease Model through the Application of Quantitative Systems Pharmacology
Authors: Pei Fen , Li Hongchun , Henderson Mark J. , Titus Steven A. , Jadhav Ajit , Simeonov Anton , Cobanoglu Murat Can , Mousavi Seyed H. , Shun Tongying , McDermott Lee , Iyer Prema , Fioravanti Michael , Carlisle Diane , Friedlander Robert M. , Bahar Ivet , Taylor D. Lansing , Lezon Timothy R. , Stern Andrew M. , Schurdak Mark E. 
Published: December 2017

AbstractQuantitative Systems Pharmacology (QSP) is a drug discovery approach that integrates computational and experimental methods in an iterative way to gain a comprehensive, unbiased understanding of disease processes to inform effective therapeutic strategies. We report the implementation of QSP to Huntington’s Disease, with the application of a chemogenomics platform to identify strategies to protect neuronal cells from mutant huntingtin induced death. Using the STHdh
Q111
cell model, we investigated the protective effects of small molecule probes having diverse canonical modes-of-action to infer pathways of neuronal cell protection connected to drug mechanism. Several mechanistically diverse protective probes were identified, most of which showed less than 50% efficacy. Specific combinations of these probes were synergistic in enhancing efficacy. Computational analysis of these probes revealed a convergence of pathways indicating activation of PKA. Analysis of phospho-PKA levels showed lower cytoplasmic levels in STHdh
Q111
cells compared to wild type STHdh
Q7
cells, and these levels were increased by several of the protective compounds. Pharmacological inhibition of PKA activity reduced protection supporting the hypothesis that protection may be working, in part, through activation of the PKA network. The systems-level studies described here can be broadly applied to any discovery strategy involving small molecule modulation of disease phenotype.
Estimation of land-surface evaporation at four forest sites across Japan with the new nonlinear complementary method
Authors: Ai Zhipin , Wang Qinxue , Yang Yonghui , Manevski Kiril , Zhao Xin , Eer Deni 
Published: December 2017

AbstractEvaporation from land surfaces is a critical component of the Earth water cycle and of water management strategies. The complementary method originally proposed by Bouchet, which describes a linear relation between actual evaporation (E), potential evaporation (Epo) and apparent potential evaporation (Epa) based on routinely measured weather data, is one of the various methods for evaporation calculation. This study evaluated the reformulated version of the original method, as proposed by Brutsaert, for forest land cover in Japan. The new complementary method is nonlinear and based on boundary conditions with strictly physical considerations. The only unknown parameter (αe) was for the first time determined for various forest covers located from north to south across Japan. The values of αe ranged from 0.94 to 1.10, with a mean value of 1.01. Furthermore, the calculated evaporation with the new method showed a good fit with the eddy-covariance measured values, with a determination coefficient of 0.78 and a mean bias of 4%. Evaluation results revealed that the new nonlinear complementary relation performs better than the original linear relation in describing the relationship between E/Epa and Epo/Epa, and also in depicting the asymmetry variation between Epa/Epo and E/Epo.
JAK/STAT and TGF-ß activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans
Authors: Kim Hunbeen , Jeong Jaeseong , Chatterjee Nivedita , Roca Carlos P. , Yoon Dahye , Kim Suhkmann , Kim Younghun , Choi Jinhee 
Published: December 2017

AbstractTitanium dioxide nanoparticles (TiO2NPs) are widely used nanoparticles, whose catalytic activity is mainly due to photoactivation. In this study, the toxicity of TiO2NPs was investigated on the nematode Caenorhabditis elegans, with and without UV activation. Comparative analyses across the four treatments revealed that UV-activated TiO2NPs led to significant reproductive toxicity through oxidative stress. To understand the underlying molecular mechanism, transcriptomics and metabolomics analyses were conducted, followed by whole-genome network-based pathway analyses. Differential expression analysis from microarray data revealed only 4 DEGs by exposure to TiO2NPs alone, compared to 3,625 and 3,286 DEGs by UV alone and UV-activated TiO2NPs, respectively. Pathway analyses suggested the possible involvement of the JAK/STAT and TGF-ß pathways in the phototoxicity of TiO2NPs, which correlated with the observation of increased gene expression of those pathways. Comparative analysis of C. elegans response across UV activation and TiO2NPs exposure was performed using loss-of-function mutants of genes in these pathways. Results indicated that the JAK/STAT pathway was specific to TiO2NPs, whereas the TGF-ß pathway was specific to UV. Interestingly, crosstalk between these pathways was confirmed by further mutant analysis. We consider that these findings will contribute to understand the molecular mechanisms of toxicity of TiO2NPs in the natural environment.
Milder degenerative effects of Carfilzomib vs. Bortezomib in the Drosophila model: a link to clinical adverse events
Authors: Tsakiri Eleni N. , Terpos Evangelos , Papanagnou Eleni-Dimitra , Kastritis Efstathios , Brieudes Vincent , Halabalaki Maria , Bagratuni Tina , Florea Bogdan I. , Overkleeft Herman S. , Scorrano Luca , Skaltsounis Alexios-Leandros , Dimopoulos Meletios A. , Trougakos Ioannis P. 
Published: December 2017

AbstractProteasome inhibitors, e.g. Bortezomib (BTZ) and Carfilzomib (CFZ), have demonstrated clinical efficacy against haematological cancers. Interestingly, several adverse effects are less common, compared to BTZ, in patients treated with CFZ. As the molecular details of these observations remain not well understood we assayed the pathophysiological effects of CFZ vs. BTZ in the Drosophila experimental model. Mass Spectrometry analyses showed that neither CFZ nor BTZ are hydrolysed in flies’ tissues, while at doses inducing similar inhibition of the rate limiting for protein breakdown chymotrypsin-like (CT-L) proteasomal activity, CFZ treatment resulted in less intense increase of oxidative stress or activation of antioxidant and proteostatic modules. Also, despite comparable cardiotoxicity likely due to disrupted mitochondrial function, CFZ did not affect developmental processes, showed minimal neuromuscular defects and reduced to a lesser extent flies’ healthspan. Studies in flies, human cancer cell lines and blood cells isolated from Multiple Myeloma patients treated with CFZ or BTZ revealed, that the increased BTZ toxicity likely relates to partial co-inhibition of the caspase-like (C-L) proteasomal activity Supportively, co-treating flies with CFZ and a C-L selective proteasome inhibitor exacerbated CFZ-mediated toxicity. Our findings provide a reasonable explanation for the differential adverse effects of CFZ and BTZ in the clinic.
Subthalamic nucleus detects unnatural android movement
Authors: Ikeda Takashi , Hirata Masayuki , Kasaki Masashi , Alimardani Maryam , Matsushita Kojiro , Yamamoto Tomoyuki , Nishio Shuichi , Ishiguro Hiroshi 
Published: December 2017

AbstractAn android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android’s slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.
Conditions and Regulation of Mixed Culture to Promote Shiraia bambusicola and Phoma sp. BZJ6 for Laccase Production
Authors: Du Wen , Sun Chunlong , Wang Jun , Xie Wenjun , Wang Baoqin , Liu Xuehong , Zhang Yumiao , Fan Yanhui 
Published: December 2017

AbstractMixing cultures induces the biosynthesis of laccase in mixed cells, produces signal molecules, and regulates the production of mixed-cell metabolites. The fungal strain, which promotes laccase production, has been isolated and screened from the host bamboos of endophytic fungi and identified as Phoma sp. BZJ6. When the culture medium is mainly composed of soluble starch, yeast extract, and Phoma sp., the laccase output can reach 4,680 U/L. Nitric oxide (NO) and reactive oxygen species (ROS) were found to promote the regulation of laccase synthesis. Plasma membrane NAD(P)H oxidase inhibitors and NO-specific quenchers can inhibit not only the accumulation of ROS induced and NO synthesis but also the biosynthesis of laccase. The results indicate that the accumulation of superoxide anion radical (O2−) and hydrogen peroxide (H2O2) induced by the mixed culture was partially dependent on NO. The mixed culture can also reduce the biomass, increase the synthesis of total phenolics and flavonoids, and enhance the activity of phenylalanine ammonia-lyase and chalcone isomerase. This phenomenon is probably the result of the activated phenylpropanoids–flavonoid pathway. Results confirmed that the mixture culture is advantageous for laccase production and revealed that NO, O2−, and H2O2 are necessary signal molecules to induce laccase synthesis.
Metabolomics reveals novel blood plasma biomarkers associated to the BRCA1-mutated phenotype of human breast cancer
Authors: Roig Bàrbara , Rodríguez-Balada Marta , Samino Sara , Lam Eric W.-F. , Guaita-Esteruelas Sandra , Gomes Ana R. , Correig Xavier , Borràs Joan , Yanes Oscar , Gumà Josep 
Published: December 2017

AbstractHereditary breast and ovarian cancer syndrome (HBOC) is partly due to the presence of mutations in the BRCA genes. Triple-negative (TN) breast cancer (BC) shares histological characteristics with germline BRCA1 mutation-associated tumours. We have investigated the metabolic profiles of human breast cancer (BC) cell lines carrying BRCA1 pathogenic mutations by non-targeted liquid chromatography coupled to mass spectrometry technology. Based on our in vitro results, we performed a targeted metabolomic analysis of plasma samples from TN HBOC patients taking into account their BRCA1 genotype. BRCA1 promoter hypermethylation and the BRCAness phenotype of BC cell lines were also studied. The purpose of this study was to determine the metabolic signature of HBOC syndrome and TNBC patients and to evaluate the potential contribution of the metabolites identified to the genetic diagnosis of breast cancer. The present results show the existence of a differential metabolic signature for BC cells based on the BRCA1 functionality. None of the studied BC cell lines presented hypermethylation of the BRCA1 promoter region. We provide evidence of the existence of free methylated nucleotides capable of distinguishing plasma samples from HBOC patients as BRCA1-mutated and BRCA1 non-mutated, suggesting that they might be considered as BRCA1-like biomarkers for TNBC and HBOC syndrome.
Active, passive, and electronic cigarette smoking is associated with asthma in adolescents
Authors: Kim So Young , Sim Songyong , Choi Hyo Geun 
Published: December 2017

AbstractThe present study investigated the associations of active, passive, and electronic cigarette (E-cigarette) smoking with asthma in Korean adolescents. We used the cross-sectional study of Korea Youth Risk Behavior Web-based Survey conducted in 2011, 2012 and 2013. Active smoking was classified into 4 groups (0 days, 1–5 days, 6–19 days, and ≥20 days a month). Passive smoking was also categorized into 4 groups (0 days, 1–2 days, 3–4 days, and ≥5 days a week). E-cigarette was defined as yes or no in the last 30 days. Age, sex, obesity, region of residence, economic level, and parental educational level were adjusted for as confounders. Smoking variables were adjusted for one another. Adjusted odd ratios (AORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression analysis with complex sampling. In total, 2.3% (4,890/216,056) of participants reported asthma in the past 12 months. Active smoking was significantly associated with asthma (AOR [95% CI] of smoking ≥20 days/month = 1.57 [1.38–1.77], P < 0.001). Passive smoking was also related with asthma (AOR [95% CI] of smoking ≥5 days/week = 1.40 [1.28–1.53], P < 0.001). E-cigarette showed positive relation with asthma, although the effects of past smoking history could not be excluded (AOR [95% CI] = 1.12 [1.01–1.26], P = 0.027).
Transcriptomic analysis of mitochondrial TFAM depletion changing cell morphology and proliferation
Authors: Lee Woo Rin , Na Heeju , Lee Seon Woo , Lim Won-Jun , Kim Namshin , Lee J. Eugene , Kang Changwon 
Published: December 2017

AbstractHuman mitochondrial transcription factor A (TFAM) has been implicated in promoting tumor growth and invasion. TFAM activates mitochondrial DNA (mtDNA) transcription, and affects nuclear gene expression through mitochondrial retrograde signaling. In this study, we investigated the effects of TFAM depletion on the morphology and transcriptome of MKN45 gastric cancer cells. Morphology alteration became visible at 12 h after TFAM knockdown: the proportion of growth-arrested polygonal cells versus oval-shaped cells increased, reaching a half-maximum at 24 h and a near-maximum at 36 h. TFAM knockdown upregulated four genes and downregulated six genes by more than threefold at 24 h and similarly at 48 h. Among them, the knockdown of CFAP65 (cilia and flagella associated protein 65) or PCK1 (cytoplasmic phosphoenolpyruvate carboxykinase) rescued the effects of TFAM depletion on cell morphology and proliferation. PCK1 was found to act downstream of CFAP65 in calcium-mediated retrograde signaling. Furthermore, mtDNA depletion by 2′,3′-dideoxycytidine was sufficient for induction of CFAP65 and PCK1 expression and inhibition of cell proliferation, but oxidative phosphorylation blockade or mitochondrial membrane potential depolarization was not. Thus, the TFAM–mtDNA–calcium–CFAP65–PCK1 axis participates in mitochondrial retrograde signaling, affecting tumor cell differentiation and proliferation.
Cardiac Depression in Pigs after Multiple Trauma – Characterization of Posttraumatic Structural and Functional Alterations
Authors: Kalbitz M. , Schwarz S. , Weber B. , Bosch B. , Pressmar J. , Hoenes F. M. , Braun C. K. , Horst K , Simon T. P. , Pfeifer R. , Störmann P. , Hummler H , Gebhard F. , Pape H. C. , Huber-Lang M. , Hildebrand F. ,   TREAT Research Group, Auner B. , Relja B. , Marzi I. , Marx G. , Haug A. , Egerer L. , Griensven M. v. , Tolba R. , Reiss K. , Uhlig S. , Teuben M. , Almahmoud K. , Kalbas Y. , Lüken H. , Almahmoud K. 
Published: December 2017

AbstractThe purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1β generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.
Electrophysiology of the rhythmic defecation program in nematode Heterorhabditis megidis
Authors: Kuznetsov Victor P. , Slivko-Koltchik Georgy A. , Voronov Dmitry A. , Panchin Yuri V. 
Published: December 2017

AbstractThe nervous system controls most rhythmic behaviors, with a remarkable exception. In Caenorhabditis elegans periodic defecation rhythm does not appear to involve the nervous system. Such oscillations are studied in detail with genetic and molecular biology tools. The small size of C. elegans cells impairs the use of standard electrophysiological methods. We studied a similar rhythmic pacemaker in the noticeably larger gut cells of Heterorhabditis megidis nematode. H. megidis defecation cycle is driven by a central pattern generator (CPG) associated with unusual all-or-none hyper-polarization “action potential”. The CPG cycle period depends on the membrane potential and CPG cycling also persisted in experiments where the membrane potential of gut cells was continuously clamped at steady voltage levels. The usual excitable tissue description does not include the endoderm or imply the generation of hyper-polarization spikes. The nematode gut cells activity calls for a reevaluation of the excitable cells definition.