bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract
Authors: Shankar Jyoti , Solis Norma V. , Mounaud Stephanie , Szpakowski Sebastian , Liu Hong , Losada Liliana , Nierman William C. , Filler Scott G. 
Published: February 2015

AbstractReceipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response.
Protein evolution analysis of S-hydroxynitrile lyase by complete sequence design utilizing the INTMSAlign software
Authors: Nakano Shogo , Asano Yasuhisa 
Published: February 2015

AbstractDevelopment of software and methods for design of complete sequences of functional proteins could contribute to studies of protein engineering and protein evolution. To this end, we developed the INTMSAlign software and used it to design functional proteins and evaluate their usefulness. The software could assign both consensus and correlation residues of target proteins. We generated three protein sequences with S-selective hydroxynitrile lyase (S-HNL) activity, which we call designed S-HNLs; these proteins folded as efficiently as the native S-HNL. Sequence and biochemical analysis of the designed S-HNLs suggested that accumulation of neutral mutations occurs during the process of S-HNLs evolution from a low-activity form to a high-activity (native) form. Taken together, our results demonstrate that our software and the associated methods could be applied not only to design of complete sequences, but also to predictions of protein evolution, especially within families such as esterases and S-HNLs.
Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen
Authors: Michaelis Martin , Agha Bishr , Rothweiler Florian , Löschmann Nadine , Voges Yvonne , Mittelbronn Michel , Starzetz Tatjana , Harter Patrick N. , Abhari Behnaz A. , Fulda Simone , Westermann Frank , Riecken Kristoffer , Spek Silvia , Langer Klaus , Wiese Michael , Dirks Wilhelm G. , Zehner Richard , Cinatl Jaroslav , Wass Mark N. , Cinatl Jindrich 
Published: February 2015

AbstractFlubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50and IC90values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells.
Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways
Authors: Li Yingchuan , Cao Yongmei , Zeng Zhen , Liang Mengfan , Xue Ying , Xi Caihua , Zhou Ming , Jiang Wei 
Published: February 2015

AbstractACE2 and Ang–(1–7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang–(1–7)/Mas axis prevents LPS–induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF–κB pathways. Primary cultured rat PMVECs were transduced with lentiviral–borne Ace2 or shRNA–Ace2 and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang–(1–7), cytokine secretion and apoptosis rates and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang–(1–7) levels, thus reducing LPS–induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK and NF–κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2–induced blockade of p38, JNK and NF–κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang–(1–7)/Mas axis has a crucial role in preventing LPS–induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF–κB pathways.
Rapid loss of lakes on the Mongolian Plateau
Authors: Tao Shengli , Fang Jingyun , Zhao Xia , Zhao Shuqing , Shen Haihua , Hu Huifeng , Tang Zhiyao , Wang Zhiheng , Guo Qinghua 
Published: February 2015

SignificanceThe Mongolian Plateau, composed mainly of Inner Mongolia in China and the Republic of Mongolia, has been experiencing remarkable lake shrinkage during the recent decades because of intensive human activities and climate changes. This study provides a comprehensive satellite-based evaluation of lake shrinkage across the plateau, and finds a greater decreasing rate of the number of lakes in Inner Mongolia than in Mongolia (34.0% vs. 17.6%) between the late 1980s and 2010, due mainly to an unsustainable mining boom and agricultural irrigation in the former. Disastrous damages to the natural systems are threatening the livelihood of local people, and we thus call for an urgent action to prevent further deterioration.
Phylogenomics with paralogs
Authors: Hellmuth Marc , Wieseke Nicolas , Lechner Marcus , Lenhof Hans-Peter , Middendorf Martin , Stadler Peter F. 
Published: February 2015

Significance
We demonstrate that the distribution of paralogs in large gene families contains in itself sufficient phylogenetic signal to infer fully resolved species phylogenies. This source of phylogenetic information is independent of information contained in orthologous sequences and is resilient against horizontal gene transfer. An important consequence is that phylogenomics data sets need not be restricted to 1:1 orthologs.
Scaling laws describe memories of host–pathogen riposte in the HIV population
Authors: Barton John P. , Kardar Mehran , Chakraborty Arup K. 
Published: February 2015

Significance
A cure or a vaccine for HIV remains elusive, and HIV is not known to be cleared by natural immune responses. Thus, one can study how a virus evolves in humans in the absence of effective directed selection pressures and harness this knowledge to inform vaccine design. We find that the sequence space accessed by circulating HIV strains is characterized by sets of sequences related by collectively coupled mutations that evade host immunity (an informative lower-dimensional representation of sequence space). These sets of sequences represent stored memories of host–pathogen combat won by the virus (analogous to neural networks) and obey power law scaling. The collective escape pathways we reveal must be thwarted by an effective vaccine.
A conserved amphipathic helix is required for membrane tubule formation by Yop1p
Authors: Brady Jacob P. , Claridge Jolyon K. , Smith Peter G. , Schnell Jason R. 
Published: February 2015

Significance
The first structural studies, to our knowledge, of a reticulon homology domain (RHD), which is essential for maintaining smooth endoplasmic reticulum (ER) tubules and the edges of ER sheets, are described. We show here that the RHD of the protein Yop1p from the YOP1 gene has hydrophobic helices long enough to cross the membrane fully but contains a previously uncharacterized amphipathic helix (APH) that is necessary for membrane tubule formation. The APH is highly conserved in its amino acid properties and its location relative to the RHD both in the DP1 (deleted in polyposis) and reticulon families. These results place the DP1/reticulon proteins into the large and growing class of membrane-remodeling proteins that use APHs to influence membrane curvature.
Crossovers are associated with mutation and biased gene conversion at recombination hotspots
Authors: Arbeithuber Barbara , Betancourt Andrea J. , Ebner Thomas , Tiemann-Boege Irene 
Published: February 2015

Significance
We present experimental evidence showing that meiosis is an important source of germline mutations. Because sites of meiotic recombination experience recurrent double-strand breaks at hotspots, recombination has been previously suspected to be mutagenic. Yet inferences made from sequence comparisons have not found strong evidence for a mutagenic effect of recombination. Here, we directly sequenced a large number of single sperm DNA molecules and found more new mutations in molecules with a crossover than in molecules without a recombination event. We also observed that GC alleles are transmitted more often than AT alleles at polymorphic sites. Our data demonstrate that both mutagenesis and biased transmission occur during crossing over in meiosis and are important modifiers of the sequence content at recombination hotspots.
Glycosylation profiles determine extravasation and disease-targeting properties of armed antibodies
Authors: Venetz Dario , Hess Christian , Lin Chia-wei , Aebi Markus , Neri Dario 
Published: February 2015

Significance
Therapeutic antibodies represent the largest and fastest growing class of biopharmaceuticals. There is a trend in moving from intact antibodies toward “armed” antibody products, in which the antibody moiety serves as pharmacodelivery vehicle. The impact of glycosylation on the targeting performance of armed antibodies is still largely unknown. Our article sheds light on the surprising finding that relatively small variations in glycostructures and sialic acid content can have dramatic effects on therapeutic agent performance. A better understanding of the impact of glycosylation on pharmaceutical activity is likely to be relevant not only for future antibody development activities, but also for changes in current manufacturing processes and for the development of biosimilar products.
Plasma butyrylcholinesterase regulates ghrelin to control aggression
Authors: Chen Vicky Ping , Gao Yang , Geng Liyi , Parks Robin J. , Pang Yuan-Ping , Brimijoin Stephen 
Published: February 2015

Significance
Butyrylcholinesterase (BChE), a common plasma enzyme, has been known for decades but its real physiological roles are just beginning to emerge. Although BChE eliminates the neurotransmitter acetylcholine, it is not vital for locomotion, cognition, or other cholinergic functions. Nevertheless, we now find that circulating BChE has a large impact on aggressive behavior in mice that is attributable to its ability to inactivate ghrelin, a peptide hormone involved in hunger, feeding, and stress. A key observation was decreased fighting among group-housed male mice overexpressing BChE after viral gene transfer. In contrast, BChE knockout mice exhibited increased fighting. These effects mirrored changes in plasma levels of active ghrelin. Controlling them might offer therapeutic potential for certain behavioral disorders.
Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk
Authors: Feng Mingye , Chen James Y. , Weissman-Tsukamoto Rachel , Volkmer Jens-Peter , Ho Po Yi , McKenna Kelly M. , Cheshier Samuel , Zhang Michael , Guo Nan , Gip Phung , Mitra Siddhartha S. , Weissman Irving L. 
Published: February 2015

Significance
Macrophage-mediated programmed cell removal (PrCR) plays an essential role in tumor surveillance and elimination. Blockade of the don't-eat-me signal CD47 on tumor cells allows already expressed eat-me signals to induce PrCR to eliminate tumor cells. To date the molecular mechanism by which macrophages recognize and phagocytose tumor cells remains unclear. This paper demonstrates that the activation of Toll-like receptor (TLR) pathways in macrophages induces the phosphorylation of Bruton's tyrosine kinase (Btk), which catalyzes cell-surface exposure of calreticulin. Calreticulin on or secreted by macrophages plays a critical role in mediating adjacent tumor cell recognition and phagocytosis. These findings reveal a strategy to enhance the efficacy of PrCR through a combination of TLR/Btk activation and CD47 blockade, and advance our understanding of the underlying mechanism of macrophage-mediated PrCR of tumor cells.
Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients
Authors: Jiang Peiyong , Chan Carol W. M. , Chan K. C. Allen , Cheng Suk Hang , Wong John , Wong Vincent Wai-Sun , Wong Grace L. H. , Chan Stephen L. , Mok Tony S. K. , Chan Henry L. Y. , Lai Paul B. S. , Chiu Rossa W. K. , Lo Y. M. Dennis 
Published: February 2015

SignificanceWe used massively parallel sequencing to study the size profiles of plasma DNA samples at single-base resolution and in a genome-wide manner. We used chromosome arm-levelz-score analysis (CAZA) to identify tumor-derived plasma DNA for studying their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These findings have shed light on fundamental biological characteristics of plasma DNA and related diagnostic applications for cancer.
GenoExp: a web tool for predicting gene expression levels from single nucleotide polymorphisms
Authors: Manor Ohad , Segal Eran 
Published: January 2015

Abstract
Summary: Understanding the effect of single nucleotide polymorphisms (SNPs) on the expression level of genes is an important goal. We recently published a study in which we devised a multi-SNP predictive model for gene expression in Lymphoblastoid cell lines (LCL), and showed that it can robustly predict the expression of a small number of genes in test individuals. Here, we validate the generality of our models by predicting expression profiles for genes in LCL in an independent study, and extend the pool of predictable genes for which we are able to explain more than 25% of their expression variability to 232 genes across 14 different cell types. As the number of people who obtained their SNP profiles through companies such as 23andMe is rising rapidly, we developed GenoExp , a web-based tool in which users can upload their individual SNP data and obtain predicted expression levels for the set of predictable genes across the 14 different cell types. Our tool thus allows users with biological knowledge to study the possible effects that their set of SNPs might have on these genes and predict their cell-specific expression levels relative to the population average.
Availability and implementation: GenoExp is freely available at http://genie.weizmann.ac.il/pubs/GenoExp/ .
Contact: eran.segal@weizmann.ac.il
Supplementary information: Supplementary data are available at Bioinformatics online.
RAMPART: a workflow management system for
de novo
genome assembly
Authors: Mapleson Daniel , Drou Nizar , Swarbreck David 
Published: January 2015

Abstract
Motivation: The de novo assembly of genomes from whole- genome shotgun sequence data is a computationally intensive, multi-stage task and it is not known a priori which methods and parameter settings will produce optimal results. In current de novo assembly projects, a popular strategy involves trying many approaches, using different tools and settings, and then comparing and contrasting the results in order to select a final assembly for publication.
Results: Herein, we present RAMPART, a configurable workflow management system for de novo genome assembly, which helps the user identify combinations of third-party tools and settings that provide good results for their particular genome and sequenced reads. RAMPART is designed to exploit High performance computing environments, such as clusters and shared memory systems, where available.
Availability and implementation: RAMPART is available under the GPLv3 license at: https://github.com/TGAC/RAMPART .
Contact: daniel.mapleson@tgac.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online. In addition, the user manual is available online at: http://rampart.readthedocs.org/en/latest .
NetExplore: a web server for modeling small network motifs
Authors: Papatsenko Dmitri , Lemischka Ihor R. 
Published: January 2015

Abstract
Motivation: Quantitative and qualitative assessment of biological data often produces small essential recurrent networks, containing 3–5 components called network motifs. In this context, model solutions for small network motifs represent very high interest.
Results: Software package NetExplore has been created in order to generate, classify and analyze solutions for network motifs including up to six network components. NetExplore allows plotting and visualization of the solution's phase spaces and bifurcation diagrams.
Availability and implementation: The current version of NetExplore has been implemented in Perl-CGI and is accessible at the following locations: http://line.bioinfolab.net/nex/NetExplore.htm and http://nex.autosome.ru/nex/NetExplore.htm .
Contact: dmitri.papatsenko@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Omics Pipe: a community-based framework for reproducible multi-omics data analysis
Authors: Fisch Kathleen M. , Meißner Tobias , Gioia Louis , Ducom Jean-Christophe , Carland Tristan M. , Loguercio Salvatore , Su Andrew I. 
Published: January 2015

Abstract
Motivation: Omics Pipe ( http://sulab.scripps.edu/omicspipe ) is a computational framework that automates multi-omics data analysis pipelines on high performance compute clusters and in the cloud. It supports best practice published pipelines for RNA-seq, miRNA-seq, Exome-seq, Whole-Genome sequencing, ChIP-seq analyses and automatic processing of data from The Cancer Genome Atlas (TCGA). Omics Pipe provides researchers with a tool for reproducible, open source and extensible next generation sequencing analysis. The goal of Omics Pipe is to democratize next-generation sequencing analysis by dramatically increasing the accessibility and reproducibility of best practice computational pipelines, which will enable researchers to generate biologically meaningful and interpretable results.
Results: Using Omics Pipe, we analyzed 100 TCGA breast invasive carcinoma paired tumor-normal datasets based on the latest UCSC hg19 RefSeq annotation. Omics Pipe automatically downloaded and processed the desired TCGA samples on a high throughput compute cluster to produce a results report for each sample. We aggregated the individual sample results and compared them to the analysis in the original publications. This comparison revealed high overlap between the analyses, as well as novel findings due to the use of updated annotations and methods.
Availability and implementation: Source code for Omics Pipe is freely available on the web ( https://bitbucket.org/sulab/omics_pipe ). Omics Pipe is distributed as a standalone Python package for installation ( https://pypi.python.org/pypi/omics_pipe ) and as an Amazon Machine Image in Amazon Web Services Elastic Compute Cloud that contains all necessary third-party software dependencies and databases ( https://pythonhosted.org/omics_pipe/AWS_installation.html ).
Contact: asu@scripps.edu or kfisch@ucsd.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
Dizzy-Beats: a Bayesian evidence analysis tool for systems biology
Authors: Aitken Stuart , Kilpatrick Alastair M. , Akman Ozgur E. 
Published: January 2015

Abstract
Motivation: Model selection and parameter inference are complex problems of long-standing interest in systems biology. Selecting between competing models arises commonly as underlying biochemical mechanisms are often not fully known, hence alternative models must be considered. Parameter inference yields important information on the extent to which the data and the model constrain parameter values.
Results: We report Dizzy-Beats, a graphical Java B ayesian e vidence a nalysis t ool implementing nested s ampling - an algorithm yielding an estimate of the log of the Bayesian evidence Z and the moments of model parameters, thus addressing two outstanding challenges in systems modelling. A likelihood function based on the L1 -norm is adopted as it is generically applicable to replicated time series data.
Availability and implementation: http://sourceforge.net/p/bayesevidence/home/Home/
Contact: s.aitken@ed.ac.uk
ClassifyR: an R package for performance assessment of classification with applications to transcriptomics
Authors: Strbenac Dario , Mann Graham J. , Ormerod John T. , Yang Jean Y.H. 
Published: February 2015

Abstract
Although a large collection of classification software packages exist in R, a new generic framework for linking custom classification functions with classification performance measures is needed. A generic classification framework has been designed and implemented as an R package in an object oriented style. Its design places emphasis on parallel processing, reproducibility and extensibility. Finally, a comprehensive set of performance measures are available to ease post-processing. Taken together, these important characteristics enable rapid and reproducible benchmarking of alternative classifiers.
Availability and implementation: ClassifyR is implemented in R and can be obtained from the Bioconductor project: http://bioconductor.org/packages/release/bioc/html/ClassifyR.html
Contact : dario.strbenac@sydney.edu.au
Supplementary information : Supplementary data are available at Bioinformatics online.