bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soil protist communities form a dynamic hub in the soil microbiome
Authors: Xiong Wu , Jousset Alexandre , Guo Sai , Karlsson Ida , Zhao Qingyun , Wu Huasong , Kowalchuk George A , Shen Qirong , Li Rong , Geisen Stefan 
Published: October 2017

Abstract
Soil microbes are essential for soil fertility. However, most studies focus on bacterial and/or fungal communities, while the top-down drivers of this microbiome composition, protists, remain poorly understood. Here, we investigated how soil amendments affect protist communities and inferred potential interactions with bacteria and fungi. Specific fertilization treatments impacted both the structure and function of protist communities. Organic fertilizer amendment strongly reduced the relative abundance of plant pathogenic protists and increased bacterivorous and omnivorous protists. The addition of individual biocontrol bacteria and fungi further altered the soil protist community composition, and eventually function. Network analysis integrating protist, bacterial and fungal community data, placed protists as a central hub in the soil microbiome, linking diverse bacterial and fungal populations. Given their dynamic response to soil management practices and key position in linking soil microbial networks, protists may provide the leverage between soil management and the enhancement of bacterial and fungal microbiota at the service of improved soil health.
Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New Modulation Possibilities
Authors: Mortier Jérémie , Prévost Julien R. C. , Sydow Dominique , Teuchert Sabine , Omieczynski Christian , Bermudez Marcel , Frédérick Raphaël , Wolber Gerhard 
Published: October 2017

AbstractMetalloenzyme arginase is a therapeutically relevant target associated with tumor growth. To fight cancer immunosuppression, arginase activity can be modulated by small chemical inhibitors binding to its catalytic center. To better understand molecular mechanisms of arginase inhibition, a careful computer-aided mechanistic structural investigation of this enzyme was conducted. Using molecular dynamics (MD) simulations in the microsecond range, key regions of the protein active site were identified and their flexibility was evaluated and compared. A cavity opening phenomenon was observed, involving three loops directly interacting with all known ligands, while metal coordinating regions remained motionless. A novel dynamic 3D pharmacophore analysis method termed dynophores has been developed that allows for the construction of a single 3D-model comprising all ligand-enzyme interactions occurring throughout a complete MD trajectory. This new technique for the in silico study of intermolecular interactions allows for loop flexibility analysis coupled with movements and conformational changes of bound ligands. Presented MD studies highlight the plasticity of the size of the arginase active site, leading to the hypothesis that larger ligands can enter the cavity of arginase. Experimental testing of a targeted fragment library substituted by different aliphatic groups validates this hypothesis, paving the way for the design of arginase inhibitors with novel binding patterns.
Induced seismicity closed-form traffic light system for actuarial decision-making during deep fluid injections
Authors: Mignan A. , Broccardo M. , Wiemer S. , Giardini D. 
Published: October 2017

AbstractThe rise in the frequency of anthropogenic earthquakes due to deep fluid injections is posing serious economic, societal, and legal challenges to many geo-energy and waste-disposal projects. Existing tools to assess such problems are still inherently heuristic and mostly based on expert elicitation (so-called clinical judgment). We propose, as a complementary approach, an adaptive traffic light system (ATLS) that is function of a statistical model of induced seismicity. It offers an actuarial judgement of the risk, which is based on a mapping between earthquake magnitude and risk. Using data from six underground reservoir stimulation experiments, mostly from Enhanced Geothermal Systems, we illustrate how such a data-driven adaptive forecasting system could guarantee a risk-based safety target. The proposed model, which includes a linear relationship between seismicity rate and flow rate, as well as a normal diffusion process for post-injection, is first confirmed to be representative of the data. Being integrable, the model yields a closed-form ATLS solution that is both transparent and robust. Although simulations verify that the safety target is consistently ensured when the ATLS is applied, the model from which simulations are generated is validated on a limited dataset, hence still requiring further tests in additional fluid injection environments.
Prediction of Treatment Response for Combined Chemo- and Radiation Therapy for Non-Small Cell Lung Cancer Patients Using a Bio-Mathematical Model
Authors: Geng Changran , Paganetti Harald , Grassberger Clemens 
Published: October 2017

AbstractThe goal of this work was to develop a mathematical model to predict Kaplan–Meier survival curves for chemotherapy combined with radiation in Non-Small Cell Lung Cancer patients for use in clinical trial design. The Gompertz model was used to describe tumor growth, radiation effect was simulated by the linear-quadratic model with an α/β-ratio of 10, and chemotherapy effect was based on the log-cell kill model. To account for repopulation during treatment, we considered two independent methods: 1) kickoff-repopulation using exponential growth with a decreased volume doubling time, or 2) Gompertz-repopulation using the gradually accelerating growth rate with tumor shrinkage. The input parameters were independently estimated by fitting to the SEER database for untreated tumors, RTOG-8808 for radiation only, and RTOG-9410 for sequential chemo-radiation. Applying the model, the benefit from concurrent chemo-radiation comparing to sequential for stage III patients was predicted to be a 6.6% and 6.2% improvement in overall survival for 3 and 5-years respectively, comparing well to the 5.3% and 4.5% observed in RTOG-9410. In summary, a mathematical model was developed to model tumor growth over extended periods of time, and can be used for the optimization of combined chemo-radiation scheduling and sequencing.
Motifs in the tau protein that control binding to microtubules and aggregation determine pathological effects
Authors: Lathuilière Aurélien , Valdés Pamela , Papin Stéphanie , Cacquevel Matthias , Maclachlan Catherine , Knott Graham W. , Muhs Andreas , Paganetti Paolo , Schneider Bernard L. 
Published: October 2017

AbstractTau pathology is associated with cognitive decline in Alzheimer’s disease, and missense tau mutations cause frontotemporal dementia. Hyperphosphorylation and misfolding of tau are considered critical steps leading to tauopathies. Here, we determine how motifs controlling conformational changes in the microtubule-binding domain determine tau pathology in vivo. Human tau was overexpressed in the adult mouse forebrain to compare variants carrying residues that modulate tau propensity to acquire a β-sheet conformation. The P301S mutation linked to frontotemporal dementia causes tau aggregation and rapidly progressing motor deficits. By comparison, wild-type tau becomes heavily hyperphosphorylated, and induces behavioral impairments that do not progress over time. However, the behavioral defects caused by wild-type tau can be suppressed when β-sheet breaking proline residues are introduced in the microtubule-binding domain of tau. This modification facilitates tau interaction with microtubules, as shown by lower levels of phosphorylation, and by the enhanced protective effects of mutated tau against the severing of the cytoskeleton in neurons exposed to vinblastine. Altogether, motifs that are critical for tau conformation determine interaction with microtubules and subsequent pathological modifications, including phosphorylation and aggregation.
Development and validation of a risk prediction model for work disability: multicohort study
Authors: Airaksinen Jaakko , Jokela Markus , Virtanen Marianna , Oksanen Tuula , Pentti Jaana , Vahtera Jussi , Koskenvuo Markku , Kawachi Ichiro , Batty G. David , Kivimäki Mika 
Published: October 2017

AbstractWork disability affects quality of life, earnings, and opportunities to contribute to society. Work characteristics, lifestyle and sociodemographic factors have been associated with the risk of work disability, but few multifactorial algorithms exist to identify individuals at risk of future work disability. We developed and validated a parsimonious multifactorial score for the prediction of work disability using individual-level data from 65,775 public-sector employees (development cohort) and 13,527 employed adults from a general population sample (validation cohort), both linked to records of work disability. Candidate predictors for work disability included sociodemographic (3 items), health status and lifestyle (38 items), and work-related (43 items) variables. A parsimonious model, explaining > 99% of the variance of the full model, comprised 8 predictors: age, self-rated health, number of sickness absences in previous year, socioeconomic position, chronic illnesses, sleep problems, body mass index, and smoking. Discriminative ability of a score including these predictors was high: C-index 0.84 in the development and 0.83 in the validation cohort. The corresponding C-indices for a score constructed from work-related predictors (age, sex, socioeconomic position, job strain) were 0.79 and 0.78, respectively. It is possible to identify reliably individuals at high risk of work disability by using a rapidly-administered prediction score.
Network analysis of EMT and MET micro-RNA regulation in breast cancer
Authors: Drago-García Diana , Espinal-Enríquez Jesús , Hernández-Lemus Enrique 
Published: October 2017

AbstractOver the last years, microRNAs (miRs) have shown to be crucial for breast tumour establishment and progression. To understand the influence that miRs have over transcriptional regulation in breast cancer, we constructed mutual information networks from 86 TCGA matched breast invasive carcinoma and control tissue RNA-Seq and miRNA-Seq sequencing data. We show that miRs are determinant for tumour and control data network structure. In tumour data network, miR-200, miR-199 and neighbour miRs seem to cooperate on the regulation of the acquisition of epithelial and mesenchymal traits by the biological processes: Epithelial-Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET). Despite structural differences between tumour and control networks, we found a conserved set of associations between miR-200 family members and genes such as VIM, ZEB-1/2 and TWIST-1/2. Further, a large number of miRs observed in tumour network mapped to a specific chromosomal location in DLK1-DIO3 (Chr14q32); some of those miRs have also been associated with EMT and MET regulation. Pathways related to EMT and TGF-beta reinforce the relevance of miR-200, miR-199 and DLK1-DIO3 cluster in breast cancer. With this approach, we stress that miR inclusion in gene regulatory network construction improves our understanding of the regulatory mechanisms underlying breast cancer biology.
Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries
Authors: Guan Xue Li , Mäser Pascal 
Published: October 2017

AbstractTrypanosomatids are parasitic protozoa which cause a spectrum of diseases, including trypanosomiasis and leishmaniasis, affecting millions of humans and animals worldwide. The surface of most protozoan parasites is heavily decorated with lipids and lipid-anchored molecules, forming protective barriers and acting as virulence factors during infection. Sphingolipids (SP) are major components of eukaryotic biomembranes, which play important roles in structural integrity, energy homeostasis and signaling. However, the precise chemical composition of SP in pathogens as well as their biochemical pathways and functions remain poorly characterized. Here, we present the first system-scale analyses of SP found in a panel of 7 trypanosomatids, including Leishmania donovani, Trypanosoma brucei and Trypanosoma cruzi. We characterized the structure of aminoethylphosphonate-containing ceramides, which are found exclusively in stercorarian Trypanosoma. Employing the sensitive and semi-quantitative sphingolipidomics approach that we developed, we report the detection of over 300 molecular species of SP, and identified unique metabolic signatures which serve as discriminants of the pathogens based on their taxonomy and lifecycle stages. The deep sphingolipidome presented here is an important biochemical and technological resource for future works to dissect SP metabolism and functions in these medically and agriculturally relevant systems.
Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice
Authors: Watabe Takahisa , Xu Ming , Watanabe Miho , Nabekura Junichi , Higuchi Taiga , Hori Karin , Sato Mitsuo P. , Nin Fumiaki , Hibino Hiroshi , Ogawa Kaoru , Masuda Masatsugu , Tanaka Kenji F. 
Published: October 2017

AbstractIdentification of the causal effects of specific proteins on recurrent and partially reversible hearing loss has been difficult because of the lack of an animal model that provides reversible gene knockdown. We have developed the transgenic mouse line Actin-tTS::Nkcc1tetO/tetO for manipulatable expression of the cochlear K+ circulation protein, NKCC1. Nkcc1 transcription was blocked by the binding of a tetracycline-dependent transcriptional silencer to the tetracycline operator sequences inserted upstream of the Nkcc1 translation initiation site. Administration of the tetracycline derivative doxycycline reversibly regulated Nkcc1 knockdown. Progeny from pregnant/lactating mothers fed doxycycline-free chow from embryonic day 0 showed strong suppression of Nkcc1 expression (~90% downregulation) and Nkcc1 null phenotypes at postnatal day 35 (P35). P35 transgenic mice from mothers fed doxycycline-free chow starting at P0 (delivery) showed weaker suppression of Nkcc1 expression (~70% downregulation) and less hearing loss with mild cochlear structural changes. Treatment of these mice at P35 with doxycycline for 2 weeks reactivated Nkcc1 transcription to control levels and improved hearing level at high frequency; i.e., these doxycycline-treated mice exhibited partially reversible hearing loss. Thus, development of the Actin-tTS::Nkcc1tetO/tetO transgenic mouse line provides a mouse model for the study of variable hearing loss through reversible knockdown of Nkcc1.
Electrochemical Magnetization Switching and Energy Storage in Manganese Oxide filled Carbon Nanotubes
Authors: Ottmann Alexander , Scholz Maik , Haft Marcel , Thauer Elisa , Schneider Philip , Gellesch Markus , Nowka Christian , Wurmehl Sabine , Hampel Silke , Klingeler Rüdiger 
Published: October 2017

AbstractThe ferrimagnetic and high-capacity electrode material Mn3O4 is encapsulated inside multi-walled carbon nanotubes (CNT). We show that the rigid hollow cavities of the CNT enforce size-controlled nanoparticles which are electrochemically active inside the CNT. The ferrimagnetic Mn3O4 filling is switched by electrochemical conversion reaction to antiferromagnetic MnO. The conversion reaction is further exploited for electrochemical energy storage. Our studies confirm that the theoretical reversible capacity of the Mn3O4 filling is fully accessible. Upon reversible cycling, the Mn3O4@CNT nanocomposite reaches a maximum discharge capacity of 461 mA h g−1 at 100 mA g−1 with a capacity retention of 90% after 50 cycles. We attribute the good cycling stability to the hybrid nature of the nanocomposite: (1) Carbon encasements ensure electrical contact to the active material by forming a stable conductive network which is unaffected by potential cracks of the encapsulate. (2) The CNT shells resist strong volume changes of the encapsulate in response to electrochemical cycling, which in conventional (i.e., non-nanocomposite) Mn3O4 hinders the application in energy storage devices. Our results demonstrate that Mn3O4 nanostructures can be successfully grown inside CNT and the resulting nanocomposite can be reversibly converted and exploited for lithium-ion batteries.
Altered behavioral and amygdala habituation in high-functioning adults with autism spectrum disorder: an fMRI study
Authors: Tam Friederike I. , King Joseph A. , Geisler Daniel , Korb Franziska M. , Sareng Juliane , Ritschel Franziska , Steding Julius , Albertowski Katja U. , Roessner Veit , Ehrlich Stefan 
Published: October 2017

AbstractHabituation to repeatedly presented stimuli is an important adaptive property of the nervous system. Autism spectrum disorder (ASD) has been associated with reduced neural habituation, for example in the amygdala, which may be related to social impairments. The main focus of this study was to investigate habituation effects on the level of behavioral responses as well as amygdala responses in adults with ASD during a working memory task flanked by task-irrelevant face stimuli. Twenty-two patients with high-functioning autism and 24 healthy controls (HC) were included in this functional magnetic resonance imaging (fMRI) study. We employed an established habituation index to investigate habituation effects. Suggestive of altered habituation, the habituation index showed a decrement of reaction time over the course of the experiment in the HC but not in the ASD group. Similarly, an expected pattern of habituation was evident in amygdala activation in HC but absent in ASD participants. These results provide evidence that habituation may be altered not only on a neural, but also on a behavioral level in ASD. While more research is needed to develop a better understanding of the underlying mechanisms, the current findings support the possibility that deficient habituation may be a biomarker of ASD.
Using quartz sand to enhance the removal efficiency of M. aeruginosa by inorganic coagulant and achieve satisfactory settling efficiency
Authors: Pei Haiyan , Jin Yan , Xu Hangzhou , Ma Chunxia , Sun Jiongming , Li Hongmin 
Published: October 2017

AbstractIn this study, low-cost and non-polluting quartz sand was respectively mixed with AlCl3, FeCl3 and PAFC to synergistically remove Microcystis aeruginosa. Results showed that quartz sand could markedly increase the algae removal efficiency and decrease the coagulant doses. The increase of removal efficiency with AlCl3 and FeCl3 was only due to the enhancement of floc density by the quartz sand. However, the removal efficiency with PAFC was increased not only by the enhanced floc density, but also by the enlarged floc size. Flocs from 50 mg/L sand addition were larger than that with other sand doses, which was on account of the appropriate enhancement of collision efficiency at this dose. After coagulation, the extracellular organic matter (EOM) and microcystins (MCs) in system with quartz sand was remarkably reduced. That’s because quartz sand can enhance the coagulation so as to improve capping the EOM and MCs in flocs during coagulation process. Owing to 200 mg/L quartz sand could damage the cell’s membrane during coagulation proces, algal cells in the system lysed two days earlier than with 50 mg/L sand during flocs storage. In addition, cells with PAFC incurred relatively moderate cellular oxidative damage and could remain intact for longer time.
Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells
Authors: Wang Guangli , Zeng Yao , Chen Shaoying , Li Deling , Li Wei , Zhou Yanchun , Singer Robert H. , Gu Wei 
Published: October 2017

AbstractTFPI-2 has recently been recognized as a tumor suppressor, which not only plays a fundamental role in modulation of ECM integrity, but also involves the regulation of many oncogenes. In this study, we investigated the potential mechanism of TFPI-2 in the suppression of breast cancer growth and invasion. We showed that, with either over-expression of TFPI-2 or after treatment with exogenous rTFPI-2, breast cancer cells exhibited reduced proliferation and invasion. We demonstrated that in addition to being secreted, TFPI-2 was also distributed throughout the cytoplasm and nucleus. Nuclear localization of TFPI-2 contributed to inhibition of MMP-2 mRNA expression, which could be reversed after the nuclear localization signal was deleted. In the nucleus, interaction of TFPI-2 with Ap-2α attenuated the binding of AP-2α to the MMP-2 promoter, therefore reducing the transcriptional activity of the gene. Our results suggest that one of the mechanisms by which TFPI-2 inhibits breast cancer cell invasion could be via the regulation of MMP-2 gene transcription.
Magnetic field topology and chemical spot distributions of the Ap star HD 119419
Authors: Rusomarov N. , Kochukhov O. , Lundin A. 
Published: October 2017

Context.Analysis of high-resolution spectropolarimetric time-series observations of early-type magnetic stars is currently the most advanced method of obtaining detailed information on their surface magnetic field topologies and horizontal spot distributions.Aims.In this study we analyse a new set of high-quality full Stokes vector observations of the magnetic Ap star HD 119419 – a member of the 14 Myr old Lower Cen-Cru association – for the purpose of studying the surface field topology and mapping the chemical abundance spots.Methods.We made use of the circular and linear polarisation data collected for HD 119419 with the HARPSpol instrument at the ESO 3.6-m telescope. These observations were analysed with a multi-line magnetic diagnostic technique and modelled in detail with a Magnetic Doppler imaging (MDI) code.Results.We present a new set of high-precision mean longitudinal magnetic field measurements and derive a revised stellar rotational period by comparing our measurements with the literature data. We also redetermine the basic stellar atmospheric parameters. Our four Stokes parameter magnetic inversions reveal a moderately complex surface field topology with a mean field strength of 18 kG and a maximum local strength of 24 kG. A poloidal dipolar component dominates the magnetic energy spectrum of the surface field in HD 119419. However, significant contributions of the higher-order spherical harmonic components are also present. We show that the dipole plus quadrupole part of the reconstructed field geometry is incapable of reproducing the observed amplitudes and shapes of the StokesQandUprofiles. The chemical abundance distributions of Fe, Cr, Ti, and Nd, derived self-consistently with the magnetic field geometry, are characterised by large abundance gradients and a lack of clear correlation with the magnetic field structure.Conclusions.This full Stokes vector analysis of HD 119419 extends the modern hot-star magnetic mapping investigations to an open cluster Ap star with a well-determined age. Further, MDI studies of cluster members will allow us to study the field topologies and chemical abundance spots as a function of stellar age.