bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation
Authors: Matsumoto Hirotaka , Kiryu Hisanori , Furusawa Chikara , Ko Minoru S H , Ko Shigeru B H , Gouda Norio , Hayashi Tetsutaro , Nikaido Itoshi 
Published: April 2017

Abstract

Motivation
The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNA-Seq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation.

Results
In this study, we developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. We applied SCODE to three single-cell RNA-Seq datasets and confirmed that SCODE can reconstruct observed expression dynamics. We evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. We also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, our algorithm provides a promising approach for further single-cell differentiation analyses.

Availability and Implementation
The R source code of SCODE is available at https://github.com/hmatsu1226/SCODE

Supplementary information
Supplementary data are available at Bioinformatics online.
Non-surgical management of early-stage lung cancer
Authors: Brown Jim , Navani Neal 
Published: April 2017

Abstract
As low-dose computed tomography screening of ‘high-risk’ smokers is occurring with increasing frequency, the incidental discovery of solitary pulmonary nodules is becoming more frequent, and lung cancer multidisciplinary teams are now often faced with balancing risk and benefit when making decisions regarding the radical treatment of patients with a clinical diagnosis of early lung cancer but borderline fitness. Surgery offers the best prospect of cure but is associated with significant mortality and morbidity; the elderly and frail experience more toxicity and a greater impact on the quality of life. This chapter reviews the criteria for assessing surgical fitness and examines the evidence for minimally invasive and ablative techniques for the treatment of early peripheral lung cancer in the medically inoperable patient.
Occupational lung disease
Authors: Feary Johanna , Szram Joanna , Cullinan Paul 
Published: April 2017

Abstract
Occupational lung diseases are under-recognized by most general (and respiratory) physicians. When affected individuals are of working age, the diagnosis can result in significant socio-economic consequences. A comprehensive knowledge of all occupational lung diseases is beyond the remit of most respiratory physicians, but an understanding of the relationships between work and disease is crucial to ensure that cases are not missed. This chapter presents two contrasting cases. The first is a ‘traditional’ case of occupational asthma, the most commonly reported occupational lung disease in the United Kingdom (as well as in most ‘developed world’ countries). The second case describes a rare disease (obliterative bronchiolitis) recently linked to a few select work exposures, highlighting the complexity of establishing causation in suspected occupational disease, particularly one uncommon in the general population. An occupational history should be taken in all cases of respiratory disease; access to specialist advice is freely available and frequently invaluable.
Tuberculosis
Authors: Russell Georgina , Kon Onn Min 
Published: April 2017

Abstract
Tuberculosis is an important infection globally, with 1.45 million deaths attributed to tuberculosis in 2010 by the World Health Organization. Respiratory physicians need to be familiar with the varied presentations and management of this disease. In addition, the proportion of cases now presenting with extrapulmonary disease are approximately half of all cases, and of particular relevance is mediastinal node tuberculosis which represents about 10% of all cases of tuberculosis in the United Kingdom. This chapter presents the case of a patient with miliary tuberculosis who developed significant drug toxicities with antituberculous therapy. The chapter reviews the role of different investigations in making a diagnosis, including the role of the Mantoux test and interferon-gamma release assays, and discusses the often challenging job of contact tracing. Finally, the chapter reviews the management of both sensitive and drug-resistant disease, along with how to manage adverse drug reactions.
Personal Cancer Genome Reporter: variant interpretation report for precision oncology
Authors: Nakken Sigve , Fournous Ghislain , Vodák Daniel , Aasheim Lars Birger , Myklebost Ola , Hovig Eivind 
Published: April 2017

AbstractSummaryIndividual tumor genomes pose a major challenge for clinical interpretation due to their unique sets of acquired mutations. There is a general scarcity of tools that cani)systematically interrogate cancer genomes in the context of diagnostic, prognostic, and therapeutic biomarkers,ii)prioritize and highlight the most important findings, andiii)present the results in a format accessible to clinical experts. We have developed a stand-alone, open-source software package for somatic variant annotation that integrates a comprehensive set of knowledge resources related to tumor biology and therapeutic biomarkers, both at the gene and variant level. Our application generates a tiered report that will aid the interpretation of individual cancer genomes in a clinical setting.Availability and ImplementationThe software is implemented in Python/R, and is freely available through Docker technology. Documentation, example reports, and installation instructions are accessible via the project GitHub page:https://github.com/sigven/pcgr)Contactsigven@ifi.uio.no
Proteomic Analysis Defines Kinase Taxonomies Specific for Subtypes of Breast Cancer
Authors: Collins Kyla. A. L. , Stuhlmiller Timothy. J. , Zawistowski Jon. S. , East Michael. P. , Pham Trang T. , Hall Claire R. , Goulet Daniel R. , Bevill Samantha M. , Angus Steven P. , Velarde Sara H. , Sciaky Noah , Oprea Tudor I. , Graves Lee M. , Johnson Gary L. , Gomez Shawn M. 
Published: April 2017

AbstractMultiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative, basal-like and claudin-low breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Kinases lacking defined functions in breast cancer were highly represented in the MIB-binding taxonomies. We show that these understudied kinases, whose disease associations and pharmacology are generally unexplored, are integrated in kinase signaling subnetworks with kinases that have been previously well characterized in breast cancer. Computationally it was possible to define subtypes using profiles of less than 50 of the more than 300 kinases bound to MIBs that included understudied as well as metabolic and lipid kinases. Furthermore, analysis of MIB-binding profiles established potential functional annotations for these understudied kinases. Thus, comprehensive MIBs-based capture of kinases provides a unique proteomics-based method for integration of poorly characterized kinases of the understudied kinome into functional subnetworks in breast cancer cells and tumors that is not possible using genomic strategies. The MIB-binding profiles readily defined subtype-selective differential adaptive kinome reprogramming in response to targeted kinase inhibition, demonstrating how MIB profiles can be used in determining dynamic kinome changes that result in subtype selective phenotypic state changes.
The C-terminal domain of ParB is critical for dynamic DNA binding and bridging interactions which condense the bacterial centromere
Authors: Fisher Gemma L. M. , Pastrana César L. , Higman Victoria A. , Koh Alan , Taylor James A. , Butterer Annika , Craggs Timothy D. , Sobott Frank , Murray Heath , Crump Matthew P. , Moreno-Herrero Fernando , Dillingham Mark S. 
Published: April 2017

SUMMARYThe ParB protein forms DNA bridging interactions aroundparSto form networks which condense DNA and earmark the bacterial chromosome for segregation. The mechanism underlying the formation of ParB nucleoprotein complexes is unclear. We show here that the central DNA binding domain is essential for anchoring atparS, and that this interaction is not required for DNA condensation. Structural analysis of the C-terminal domain reveals a dimer with a lysine-rich surface that binds DNA non-specifically and is essential for DNA condensationin vitro. Mutation of either the dimerisation or the DNA binding interface eliminates ParB foci formationin vivo. Moreover, the free C-terminal domain can rapidly decondense ParB networks independently of its ability to bind DNA. Our work reveals a dual role for the C-terminal domain of ParB as both a DNA binding and bridging interface, and highlights the dynamic nature of ParB networks.
“Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP”
Authors: Pawellek Andrea , Ryder Ursula , Tammsalu Triin , King Lewis J. , Kreinin Helmi , Ly Tony , Hay Ronald T. , Hartley Richard , Lamond Angus I. 
Published: April 2017

AbstractHere, we identify the plant biflavanoid hinokiflavone as an inhibitor of splicingin vitroand modulater of alternative splicing in multiple human cell lines. Hinokiflavone inhibits splicingin vitroby blocking one or more early steps of spliceosome assembly, leading to accumulation of the A complex. Multiple human cell lines treated with hinokiflavone show changes in the alternative splicing of different pre-mRNA substrates, but little or no change in transcription. They also show altered subnuclear organization, specifically of splicing factors required for A complex formation, which relocalized together with SUMO1 and SUMO2 into enlarged nuclear speckles. While most cell lines treated with hinokiflavone showed cell cycle arrest and eventual cell death, dependent on time and concentration, the promyelocytic NB4 cell line, which expresses the SUMO target PML-RARalpha fusion protein, was exquisitely sensitive to apoptosis following hinokiflavone treatment. Hinokiflavone treatment increased protein SUMOylation levels, both inin vitrosplicing reactions and in cells, with little or no effect on levels of ubiquitinylated proteins. Hinokiflavone also inhibited the catalytic activity of purifiedE. coliexpressed SUMO protease, SENP1in vitro, indicating the increase in SUMOylated proteins results primarily from inhibition of de-SUMOylation. Using a quantitative proteomics assay we identified many SUMO2 sites whose levels increased following hinokiflavone treatment, with the major targets including 6 proteins that are associated with U2 snRNP and required for A complex formation. These data identify hinokiflavone as a SUMO protease inhibitor and indicate SUMOylation of splicing factors may be important for modulating splice site selection.
A Robust Targeted Sequencing Approach for Low Input and Variable Quality DNA from Clinical Samples
Authors: So Austin P. , Vilborg Anna , Bouhlal Yosr , Koehler Ryan T. , Grimes Susan M. , Pouliot Yannick , Mendoza Daniel , Ziegle Janet , Stein Jason , Goodsaid Federico , Lucero Michael Y. , De La Vega Francisco M. , Ji Hanlee P. 
Published: April 2017

ABSTRACTNext-generation deep sequencing of gene panels is being adopted as a diagnostic test to identify actionable mutations in cancer patient samples. However, clinical samples, such as formalin-fixed, paraffin-embedded specimens, frequently provide low quantities of degraded, poor quality DNA. To overcome these issues, many sequencing assays rely on extensive PCR amplification leading to an accumulation of bias and artifacts. Thus, there is a need for a targeted sequencing assay that performs well with DNA of low quality and quantity without relying on extensive PCR amplification. We evaluate the performance of a targeted sequencing assay based on Oligonucleotide Selective Sequencing, which permits the enrichment of genes and regions of interest and the identification of sequence variants from low amounts of damaged DNA. This assay utilizes a repair process adapted to clinical FFPE samples, followed by adaptor ligation to single stranded DNA and a primer-based capture technique. Our approach generates sequence libraries of high fidelity with reduced reliance on extensive PCR amplification - this facilitates the accurate assessment of copy number alterations in addition to delivering accurate SNV and indel detection. We apply this method to capture and sequence the exons of a panel of 130 cancer-related genes, from which we obtain high read coverage uniformity across the targeted regions at starting input DNA amounts as low as 10 ng per sample. We further demonstrate the performance of this assay using a series of reference DNA samples, and by identifying sequence variants in DNA from matched clinical samples originating from different tissue types.
Secretogranin-II plays a critical role in zebrafish neurovascular modeling
Authors: Tao Binbin , Hu Hongling , Mitchell Kimberly , Chen Ji , Jia Haibo , Zhu Zuoyan , Trudeau Vance L. , Hu Wei 
Published: April 2017

Summary statementNeurons expressingsgIIbalign with central arteries in hindbrain. We show thatsgIIbis critical for neurovascular modeling the larval zebrafish mediated by MAPK and PI3K/AKT signalingin vivo.AbstractSecretoneurin (SN) is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II (SgII). In zebrafish and other teleosts there are 2 paralogs we previously namedsgIIaandsgIIb. Our results showed that neurons expressingsgIIbwere aligned with central arteries in hindbrain, demonstrating a close neurovascular association. BothsgIIb-/-andsgIIa-/-/sgIIb-/-mutant embryos were defective in hindbrain central artery development, while artery development insgIIa-/-mutant embryos was not affected. Hindbrain arterial and venous network identities were not affected insgIIb-/-mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways were inhibited insgIIb-/-mutant embryos. Injection of a synthetic SNb mRNA or delivery of the protein kinase activator N-arachidonoyl-L-serine could partially rescue the central artery developmental defects in thesgIIbmutants. This study provides the firstin vivoevidence thatsgIIbplays a critical role in neurovascular modeling the hindbrain.
Sec17 (α-SNAP) and an SM-tethering complex control the outcome of SNARE zipperingin vitroandin vivo
Authors: Schwartz Matthew L. , Nickerson Daniel P. , Lobingier Braden T. , Angers Cortney G. , Zick Michael , Merz Alexey J. 
Published: April 2017

AbstractZippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here we explore how SNARE regulators operate on discrete zippering states. The formation of a metastabletrans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 catalysis, Sec17 either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, HOPS and Vps33 accelerate SNARE zippering, particularly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially-zipped, Sec17 promotes fusion in either the presence or absence of HOPS — but with faster kinetics when HOPS is absent. Our data further indicate that Sec17 promotes fusion both through its direct penetration of the membrane and by enhancing C-terminal SNARE zippering. In a working model, the interplay among Sec17, Sec18, SMs, and SNARE zippering can explain why SM proteins are indispensable for SNARE-mediated fusionin vivo.Impact statementSec17 is shown to have divergent effects on pre-fusion SNARE complex activity, depending on the state of SNARE zippering. HOPS, an SM-tether complex, controls the outcome of Sec17-SNARE engagement. The results suggest a coherent working model for SM activityin vivo.
LncRNA-TUG1/EZH2 axis promotes cell proliferation, migration and the EMT phenotype formation through sponging miR-382
Authors: Zhao Liang , Sun Hongwei , Kong Hongru , Chen Zongjing , Chen Bicheng , Zhou Mengtao 
Published: April 2017

AbstractPancreatic carcinoma (PC) is the one of the most common and malignant cancer in the world. Despite many effort have been made in recent years, the survival rate of PC still remains unsatisfied. Therefore, investigating the mechanisms underlying the progression of PC might facilitate the development of novel treatments that improve patient prognosis. LncRNA Taurine Up–regulated Gene 1 (TUG1) was initially identified as a transcript up - regulated by taurine, siRNA - based depletion of TUG1 suppresses mouse retinal development, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in pancreatic carcinoma (PC) still needs to be further investigated. In the current study, the expression of TUG1 in the PC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and loss-of-function and gain-of-function approaches were applied to investigate the function of TUG1 in PC cell. Online database analysis tools showed that miR-382 could interact with TUG1 and we found an inverse correlation between TUG1 and miR-382 in PC specimens. Moreover, dual luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and applied biotin-avidin pulldown system further provide evidence that TUG1 directly targeted miR-382 by binding with microRNA binding site harboring in the TUG1 sequence. Furthermore, gene expression array analysis using clinical samples and RT-qPCR proposed that EZH2 was a target of miR-382 in PC. Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression at least partially through function as an endogenous ‘sponge’ by competing for miR-382 binding to regulate the miRNA target EZH2.
PTSD blood transcriptome mega-analysis: Shared inflammatory pathways across biological sex and modes of traumas
Authors: Breen Michael S. , Tylee Daniel S. , Maihofer Adam X. , Neylan Thomas C. , Mehta Divya , Binder Elisabeth , Chandler Sharon D. , Hess Jonathan L. , Kremen William S. , Risbrough Victoria B. , Woelk Christopher H. , Baker Dewleen G. , Nievergelt Caroline M. , Tsuang Ming T. , Buxbaum Joseph D. , Glatt Stephen J. 
Published: April 2017

ABSTRACTTranscriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module down-regulated in men exposed to combat traumas, one IL12-mediated signaling module up-regulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and MAPK-activity up-regulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.
A note on dynamical compensation and its relation to parameter identifiability
Authors: Karin Omer , Alon Uri , Sontag Eduardo 
Published: April 2017

AbstractWe recently identified a motif for dynamical compensation (DC) – a property where a system maintains the dynamics and steady-state of a regulated variable robust in the face of fluctuations in key parameters. Such parameters are therefore unidentifiable from measurements of the regulated variable at steady-state. On the other hand, since the models showing dynamical compensation are typically non-redundant, their parameters are identifiable from experimental data. We clarify this apparent discrepancy by requiring that the parameters of DC circuits be identifiable both away from steady-state and when measuring other system variables. We use this observation to provide a definition for DC in terms of parameter identifiability and discuss its relevance for the examples provided in Karin et al.
A role for the F-box protein HAWAIIAN SKIRT in plant miRNA function
Authors: Lang Patricia L.M. , Christie Michael D. , Dogan Ezgi , Schwab Rebecca , Hagmann Jörg , Van de Weyer Anna-Lena , Weigel Detlef 
Published: April 2017

AbstractAs regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. While a plethora of factors involved in their biogenesis and action inArabidopsis thalianahave been described, these processes and their fine-tuning are not fully understood in plants. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156 activity. We identified a new mutant allele of the F-box protein HAWAIIAN SKIRT (HWS; At3G61590),hws-5, as a suppressor of theMIM156-induced developmental and molecular phenotypes. Inhwsplants, levels of endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS - but not a truncated version lacking the F-box domain - display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants,hwsloses its delayed floral organ abscission (‘skirt’) phenotype, suggesting epistasis. Also, the overallhwstranscriptome profile partially resembles well-known miRNA mutantshyl1-2 andse-3, indicating action in a common pathway. We thus propose HWS as a novel, F-box dependent regulator of miRNA biogenesis.Summary statementHAWAIIAN SKIRT is a regulator ofArabidopsis thalianamicroRNA biogenesis and acts in an F-box-dependent manner.