bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer
Authors: Shinde Aparna , Wilmanski Tomasz , Chen Hao , Teegarden Dorothy , Wendt Michael K. 
Published: May 2018

AbstractBackground: Overcoming systemic dormancy and initiating secondary tumor grow under unique microenvironmental conditions is a major rate-limiting step in metastatic progression. Disseminated tumor cells encounter major changes in nutrient supplies and oxidative stresses compared to the primary tumor and must demonstrate significant metabolic plasticity to adapt to specific metastatic sites. Recent studies suggest that differential utilization of pyruvate sits as a critical node in determining the organotropism of metastatic breast cancer. Pyruvate carboxylase (PC) is key enzyme that converts pyruvate into oxaloacetate for utilization in gluconeogenesis and replenishment of the TCA cycle.Methods: Patient survival was analyzed with respect to gene copy number alterations and differential mRNA expression levels of PC. Expression of PC was analyzed in the MCF-10A, D2-HAN and the 4T1 breast cancer progression series under in vitro and in vivo growth conditions. PC expression was depleted via shRNAs and the impact on in vitro cell growth, mammary fat pad tumor growth, and pulmonary and non-pulmonary metastasis was assessed by bioluminescent imaging. Changes in glycolytic capacity, oxygen consumption and response to oxidative stress were quantified upon PC depletion.Results: Genomic copy number increases in PC were observed in 16-30% of metastatic breast cancer patients. High expression of PC mRNA was associated with decreased patient survival in the MCTI and METABRIC patient datasets. Enhanced expression of PC was not recapitulated in breast cancer progression models when analyzed under glucose-rich in vitro culture conditions. In contrast, PC expression was dramatically enhanced upon glucose deprivation and in vivo in pulmonary metastases. Depletion of PC led to a dramatic decrease in 4T1 pulmonary metastasis but did not affect orthotopic primary tumor growth. Tail vein inoculations confirmed the role of PC in facilitating pulmonary, but not extra-pulmonary tumor initiation. PC-depleted cells demonstrated a decrease in glycolytic capacity and oxygen consumption rates and an enhanced sensitivity to oxidative stress.Conclusions: Our studies indicate that PC is specifically required for the growth of breast cancer that has disseminated to the lungs. Overall, these findings point to the potential of targeting PC for the treatment of pulmonary metastatic breast cancer.
MTL functional connectivity predicts stimulation-induced theta power
Authors: Solomon E. A. , Gross R. , Lega B. , Sperling M. R. , Worrell G. , Sheth S. A. , Zaghloul K. A. , Jobst B. C. , Stein J. M. , Das S. , Gorniak R. , Inman C. , Seger S. , Kragel J. E. , Rizzuto D. S. , Kahana M. J. 
Published: May 2018

Abstract/SummaryFocal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked changes in theta (5-8 Hz) power, but only when stimulation was applied in or adjacent to white matter. Furthermore, these power changes aligned with control-theoretic predictions of how exogenous stimulation flows through complex networks, such as a dispersal of induced activity when functional hubs are targeted. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, but that access to structural connections is necessary to observe such effects.
The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease
Authors: Noronha Alberto , Modamio Jennifer , Jarosz Yohan , Sompairac Nicolas , Gonzàlez German Preciat , Daníelsdóttir Anna Dröfn , Krecke Max , Merten Diane , Haraldsdóttir Hulda S. , Heinken Almut , Heirendt Laurent , Magnúsdóttir Stefanía , Ravcheev Dmitry A. , Sahoo Swagatika , Gawron Piotr , Guerard Elisabeth , Fiscioni Lucia , Garcia Beatriz , Prendergast Mabel , Puente Alberto , Rodrigues Mariana , Roy Akansha , Rouquaya Mouss , Wiltgen Luca , Alise Žagare Alise , John Elisabeth , Krueger Maren , Kuperstein Inna , Zinovyev Andrei , Schneider Reinhard , Fleming Ronan M.T. , Thiele Ines 
Published: May 2018

AbstractA multitude of factors contribute to complex diseases and can be measured with “omics” methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH,http://vmh.life)database encapsulating current knowledge of human metabolism within five interlinked resources “Human metabolism”, “Gut microbiome”, “Disease”, “Nutrition”, and “ReconMaps”. The VMH captures 5,180 unique metabolites, 17,730 unique reactions, 3,288 human genes, 255 Mendelian diseases, 818 microbes, 632,685 microbial genes, and 8,790 food items. The VMH’s unique features are i) the hosting the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; ii) seven human metabolic maps for data visualization; iii) a nutrition designer; iv) a user-friendly webpage and application-programming interface to access its content; and v) user feedback option for community engagement. We demonstrate with four examples the VMH’s utility. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community.
Estimating Optimal Lysogenic Propensity for Viruses in Stressed Environments
Authors: Thakkar Devang , Saini Supreet 
Published: May 2018

Abstract.Having infected a bacterial cell, a temperate phage has to make a choice between (a) integrating itself into the bacterial genome, i.e.lysogeny, and (b) using the bacterial machinery to create multiple copies of itself and lysing the cell in the process, i.e.lysis. In order to maximize its long-term growth rate, phages need to ensure that they do not wipe off their bacterial hosts. Temperate phages have been observed to exhibit lysogenic propensities dependent on theMoI(Multiplicity of Infection), among other factors. We propose a model to estimate the propensity of lysogeny opted for by the phages in order to maximize coexistence. One possible approach to do so is to adopt a strategy that would help to attain and maintain an approximately equal proportion of phages with respect to their host. We find that the optimal fraction of phages opting for lysogeny follows a sigmoidal relationship with theMoIand is comparable to results obtained experimentally. We further assess the impact of phage and bacterial environmental stresses on the lysogenic propensity. Our results indicate that the optimal value of lysogenic propensity is greatly dependent on the intensity of these stresses.
Systems Biology Inferring edge function in protein-protein interaction networks
Authors: Esposito Daniel , Cursons Joseph , Davis Melissa 
Published: May 2018

AbstractMotivation: Post-translational modifications (PTMs) regulate many key cellular processes. Numerous studies have linked the topology of protein-protein interaction (PPI) networks to many biological phenomena such as key regulatory processes and disease. However, these methods fail to give insight in the functional nature of these interactions. On the other hand, pathways are commonly used to gain biological insight into the function of PPIs in the context of cascading interactions, sacrificing the coverage of networks for rich functional annotations on each PPI. We present a machine learning approach that uses Gene Ontology, InterPro and Pfam annotations to infer the edge functions in PPI networks, allowing us to combine the high coverage of networks with the information richness of pathways.Results: An ensemble method with a combination Logistic Regression and Random Forest classifiers trained on a high-quality set of annotated interactions, with a total of 18 unique labels, achieves high a average F1 score 0.88 despite not taking advantage of multi-label dependencies. When applied to the human interactome, our method confidently classifies 62% of interactions at a probability of 0.7 or higher.Availability: Software and data are available at https://github.com/DavisLaboratory/pyPPIContact:davis.m@wehi.edu.auSupplementary information: Supplementary data are available at Bioinformatics online.
Genome-wide analysis of genetic predisposition to Alzheimer’s disease and related sex-disparities
Authors: Nazarian Alireza , Yashin Anatoliy I. , Kulminski Alexander M. 
Published: May 2018

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained.MethodsWe investigated the genetic architecture of AD in four publicly available independent datasets through genome-wide association, transcriptome-wide association, and gene-based analyses. To explore differences in the genetic basis of AD between males and females, analyses were performed on three samples in each dataset: males and females combined, only males, or only females.ResultsOur genome-wide association analyses corroborated the associations of several previously detected AD loci and revealed novel significant associations of 54 single-nucleotide polymorphisms (SNPs) at a p-value of < 5E-06. In addition, 23 genes located outside the chromosome 19q13 region showed suggestive associations with AD at a false discovery rate of 0.05 in transcriptome-wide association and gene-based analyses. Most of the newly detected AD-associated SNPs and genes were sex specific, indicating sex disparities in the genetic basis of AD.ConclusionsOur findings, particularly the newly discovered sex-specific genetic contributors, provide novel insight into the genetic architecture of AD and can advance our understanding of its pathogenesis.
Understanding psychophysiological interaction and its relations to beta series correlation
Authors: Di Xin , Zhang Zhiguo , Biswal Bharat B 
Published: May 2018

AbstractPsychophysiological interaction (PPI) was proposed 20 years ago for study of task modulated connectivity on functional MRI (fMRI) data. A few modifications have since been made, but there remain misunderstandings on the method, as well as on its relations to a similar method named beta series correlation (BSC). Here, we explain what PPI measures and its relations to BSC. We first clarify that the interpretation of a regressor in a general linear model depends on not only itself but also on how other effects are modeled. In terms of PPI, it always reflects differences in connectivity between conditions, when the physiological variable is included as a covariate. Secondly, when there are multiple conditions, we explain how PPI models calculated from direct contrast between conditions could generate identical results as contrasting separate PPIs of each condition (a.k.a. “generalized” PPI). Thirdly, we explicit the deconvolution process that is used for PPI calculation, and how is it related to the trial-by-trial modeling for BSC, and illustrate the relations between PPI and those based upon BSC. In particular, when context sensitive changes in effective connectivity are present, they manifest as changes in correlations of observed trial-by-trial activations or functional connectivity. Therefore, BSC and PPI can detect similar connectivity differences. Lastly, we report empirical analyses using PPI and BSC on fMRI data of an event-related stop signal task to illustrate our points.
Differential integration of transcriptome and proteome identifies pan-cancer prognostic biomarkers
Authors: Schwartz Gregory W. , Petrovic Jelena , Zhou Yeqiao , Faryabi Robert B. 
Published: May 2018

AbstractHigh-throughput analysis of the transcriptome and proteome individually are used to interrogate complex oncogenic processes in cancer. However, an outstanding challenge is how to combine these complementary, yet partially disparate data sources to accurately identify tumor-specific gene-programs and clinical biomarkers. Here, we introduceinteGREATfor robust and scalable differential integration of high-throughput measurements. WithinteGREAT, each data source is represented as a co-expression network, which is analyzed to characterize the local and global structure of each node across networks.inteGREATscores the degree by which the topology of each gene in both transcriptome and proteome networks are conserved within a tumor type, yet different from other normal or malignant cells. We demonstrated the high performance ofinteGREATbased on several analyses: deconvolving synthetic networks, rediscovering known diagnostic biomarkers, establishing relationships between tumor lineages, and elucidating putative prognostic biomarkers which we experimentally validated. Furthermore, we introduce the application of a clumpiness measure to quantitatively describe tumor lineage similarity. Together,inteGREATnot only infers functional and clinical insights from the integration of transcriptomic and proteomic data sources in cancer, but also can be readily applied to other heterogeneous high-throughput data sources.inteGREATis open source and available to download fromhttps://github.com/faryabib/inteGREAT.
Reduced prefrontal synaptic connectivity and disturbed oscillatory population dynamics in the CNTNAP2 model of autism
Authors: Lazaro Maria T. , Taxidis Jiannis , Shuman Tristan , Bachmutsky Iris , Ikrar Taruna , Santos Rommel , Marcello Giuseppe M. , Mylavarapu Apoorva , Chandra Swasty , Foreman Allison , Goli Rachna , Tran Duy , Sharma Nikhil , Azhdam Michelle , Dong Hongmei , Peñagarikano Olga , Masmanidis Sotiris , Rácz Bence , Xu Xiangmin , Geschwind Daniel H. , Golshani Peyman 
Published: May 2018

ABSTRACTLoss of function mutations in CNTNAP2 cause a syndromic form of autism spectrum disorder (ASD) in humans and produce social deficits, repetitive behaviors, and seizures in mice. Yet, the functional effects of these mutations at the cellular and circuit level remain elusive. Using laser scanning photostimulation, whole-cell recordings, and electron microscopy, we found a dramatic decrease in functional excitatory and inhibitory synaptic inputs in L2/3 medial prefrontal cortex (mPFC) of Cntnap2 knock-out (KO) mice. In accordance with decreased synaptic input, KO mice displayed reduced spine and synapse densities, despite normal intrinsic excitability and dendritic complexity. To determine how this decrease in synaptic inputs alters coordination of neuronal firing patterns in vivo, we recorded mPFC local field potentials (LFP) and unit spiking in head-fixed mice during locomotion and rest. In KO mice, LFP power was not significantly altered at all tested frequencies, but inhibitory neurons showed delayed phase-firing and reduced phase-locking to delta and theta oscillations during locomotion. Excitatory neurons showed similar changes but only to delta oscillations. These findings suggest that profound ASD-related alterations in synaptic inputs can yield perturbed temporal coordination of cortical ensembles.
TRAIL (CD253) Sensitizes Human Airway Epithelial Cells to Toxin-Induced Cell Death
Authors: Rong Yinghui , Westfall Jennifer , Ehrbar Dylan , LaRocca Timothy , Mantis Nicholas J. 
Published: May 2018

ABSTRACTInhalation of ricin toxin is associated with the onset of acute respiratory distress syndrome (ARDS), characterized by hemorrhage, inflammatory exudates, and tissue edema, as well as the near complete destruction of the lung epithelium. Here we report that the Calu-3 human airway epithelial cell line is relatively impervious to the effects of ricin, with little evidence of cell death even upon exposure to microgram amounts of toxin. However, the addition of exogenous soluble TNF-Related Apoptosis Inducing Ligand (TRAIL; CD253) dramatically sensitized Calu-3 cells to ricin-induced apoptosis. Calu-3 cell killing in response to ricin and TRAIL was reduced upon the addition of caspase-8 and caspase-3/7 inhibitors, but not caspase 9 inhibitors, consistent with involvement of extrinsic apoptotic pathways in cell death. We employed nCounter Technology to define the transcriptional response of Calu-3 cells to ricin, TRAIL, and the combination of ricin plus TRAIL. An array of genes associated with inflammation-and cell death were significantly up regulated upon treatment with ricin toxin, and further amplified upon addition of TRAIL. Of particular note was IL-6, whose expression in Calu-3 cells increased 300-fold upon ricin treatment and more than 750-fold upon ricin and TRAIL treatment. IL-6 secretion by Calu-3 cells was confirmed by cytometric bead array. Based on these finding, we speculate that the severe airway epithelial cell damage observed in animal models following ricin exposure is a result of a positive feedback loop driven by pro-inflammatory cytokines like TRAIL and IL-6.
Impact of exogenous nitrogen on cyanobacterial abundance and community in oil-contaminated sediment mesocosms
Authors: Sun Kaikai , Qi Minbo , Zhu Panpan , Wang Haixia , Lu Zhenmei 
Published: May 2018

ABSTRACTHigh concentrations of crude oil are toxic to cyanobacteria but can facilitate the emergence of cyanobacterial aggregation at an appropriate concentration range; however, the exact inducing factor has never been clearly elucidated. We hypothesized that increasing exposure to elevated concentrations of nitrogen would inhibit the accumulation of cyanobacteria in oil-contaminated sediments. To test this hypothesis, we simulated an oil spill in estuarine sediment microcosms with and without the removal of nitrogen limitation by supplementation of exogenous nitrogen. An integrated MiSeq sequencing of 16S rRNA gene analysis along with metatranscriptome sequence was performed to achieve a comprehensive study of cyanobacterial blooms. The number of cyanobacterial sequences increased over time in both oil-contaminated and non-oil-contaminated sediments at different time points after 42 days of incubation. And, supplementation with a nitrogen resource could accelerate cyanobacterial blooms under uncontaminated microcosms but delay the bloom phenomenon and reduce the cyanobacterial abundance to a great degree when exposed to oil. Our results clearly illustrated that nitrogen limitation was a vital driver of the increased abundance of cyanobacteria in oil-contaminated mesocosms. In addition, the abundance and compositions of blooming cyanobacteria varied significantly among the different treatment groups, andOscillatoriamay play a potential and non-negligible role in oil-contaminated mesocosms.
Histophilus somniSurvives in Bovine Macrophages by Interfering with Phagosome-Lysosome Fusion, but Requires IbpA for Optimal Serum Resistance
Authors: Pan Yu , Tagawa Yuichi , Champion Anna , Sandal Indra , Inzana Thomas J. 
Published: May 2018

ABSTRACTHistophilus somnisurvives intracellularly in professional phagocytic cells, but the mechanism of intracellular survival is not understood. The Fic motif within the DR1/DR2 IbpA fibrillar network protein ofH. somniis cytotoxic to epithelial and phagocytic cells, which may interfere with the bactericidal activity of these cells. To determine the contribution of IbpA and Fic on resistance to host defenses, strains and mutants that lack all of or a small region ofibpAor DR1/DR2 were tested for survival in bovine monocytic cells and for serum susceptibility. A mutant lacking IbpA, but not DR1/DR2, was more susceptible to killing by antiserum than the parent.H. somnistrains expressing IbpA replicated in bovine monocytes for at least 72 hours, and were toxic for these cells. Virulent strain 2336 with transposon insertions or deletions within IbpA remained toxic for bovine monocytes. However, strain 2336 mutants lacking all ofibpAor both DR1/DR2 were not toxic to the monocytes, but survived within the monocytes for at least 72 hours. Examination of intracellular trafficking ofH. somniwith monoclonal antibodies to early and late phagosomal markers indicated that early phagosomal marker EEA-1 colocalized with both disease isolate strain 2336 and serum-sensitve mucosal isolate strain 129Pt, but only strain 2336 did not co-localize with late lysosomal marker LAMP-2 and prevented acidification of phagosomes. These results indicate that virulent isolates ofH. somniare capable of surviving within phagocytic cells through interference of phagosome-lysosome maturation. Therefore,H. somnimay be considered a permissive intracellular pathogen.
Bacterial community shift in nutrient-treated oil-bearing sandstones from the subsurface strata of an onshore oil reservoir and its potential use in Microbial Enhanced Oil Recovery
Authors: Phetcharat Thanachai , Dawkrajai Pinan , Chitov Thararat , Wongpornchai Pisanu , Saenton Schradh , Mhuantong Wuttichai , Kanokratana Pattanop , Champreda Verawat , Bovonsombut Sakunnee 
Published: May 2018

AbstractMicrobial Enhanced Oil Recovery (MEOR) is a promising strategy to improve recovery of residual oil in reservoirs, which can be performed by promoting specific indigenous microorganisms. In this study, bacterial communities and the effects of elemental nutrient treatment of oil-bearing sandstone cores originated from six oil wells of an onshore reservoir was determined by tagged 16S rRNA gene amplicon sequencing, using Ion Torrent Metagenomic Sequencing Analysis. A total number of sequences were taxonomically classified into 43 phyla, 320 families, and 584 genera, with the dominant bacterial populations being related to Deinococcus-Thermus, and Betaproteobacteria. The nutrient treatment resulted in markedly increase in the relative abundance of Gammaproteobacteria. Thermus, Acinetobacter, and Pseudomonas were the most abundant genera. To our knowledge, this is the first report on the effect of elemental nutrients on alteration of bacteria communities attached to the oil-bearing rock. It provides comprehensive data on bacterial, physical, and chemical structures within a reservoir and demonstrates how these parameters can be co-analyzed to serve as a basis for designing a MEOR process. It also provides a model of how a bacterial community in reservoirs’ strata can be altered by nutrient treatment to enhance the efficiency of MEOR applications.
Concentration-dependent reduction of planktonic- and biofilm-stateVibrio alginolyticusby the bacteriophage pVa-21
Authors: Kim Sang Guen , Giri Sib Sankar , Jun Jin Woo , Yun Saekil , Kim Hyoun Joong , Kim Sang Wha , Kang Jeong Woo , Han Se Jin , Jeong Dalsang , Park Se Chang 
Published: May 2018

AbstractThere is an increasing emergence of antibiotic-resistantVibrio alginolyticus, a zoonotic pathogen that causes mass mortality in aquatic animals as well as human infection; therefore, there is a demand for alternatives to antibiotics for treatment and prevention of infections caused by this pathogen. One possibility is through the exploitation of bacteriophages. In the present study, the bacteriophage pVa-21 belonging toMyoviridae, was isolated and characterized as a candidate biocontrol agent againstV. alginolyticus. Its morphology, host range and infectivity, growth characteristics, planktonic or biofilm lytic property, stability under various conditions, and genome were investigated. Its latent period and burst size were estimated to be approximately 70 min and 58 plaque-forming units/cell, respectively. In addition, phage pVa-21 could inhibit bacterial growth both in the planktonic and biofilm state. Furthermore, phylogenetic and genome analyses revealed that the phage is closely related to ‘phiKZ-like phages’ and can be classified as a new member of the phiKZ-like phages that infect bacteria belonging to the family Vibrionaceae.