bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features
Authors: Kai Yan , Andricovich Jaclyn , Zeng Zhouhao , Zhu Jun , Tzatsos Alexandros , Peng Weiqun 
Published: December 2017

AbstractThe CCCTC-binding zinc finger protein (CTCF)-mediated network of long-range chromatin interactions is important for genome organization and function. Although this network has been considered largely invariant, we found that it exhibits extensive cell-type-specific interactions that contribute to cell identity. Here we present Lollipop—a machine-learning framework—which predicts CTCF-mediated long-range interactions using genomic and epigenomic features. Using ChIA-PET data as benchmark, we demonstrated that Lollipop accurately predicts CTCF-mediated chromatin interactions both within and across cell-types, and outperforms other methods based only on CTCF motif orientation. Predictions were confirmed computationally and experimentally by Chromatin Conformation Capture (3C). Moreover, our approach reveals novel determinants of CTCF-mediated chromatin wiring, such as gene expression within the loops. Our study contributes to a better understanding about the underlying principles of CTCF-mediated chromatin interactions and their impact on gene expression.
Diverse functions of closely homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence
Authors: Vedula P. , Kurosaka S. , Leu N. A. , Wolf Y. I. , Shabalina S. , Wang J. , Sterling S. , Dong D. W. , Kashina A. 
Published: December 2017

Abstractβ- and γ-cytoplasmic-actin are nearly indistinguishable in their amino acid sequence, but are encoded by different genes that play non-redundant biological roles. The key determinants that drive their functional distinction are unknown. Here we tested the hypothesis that β- and γ-actin functions are defined by their nucleotide, rather than their amino acid sequence, using targeted editing of the mouse genome. Although previous studies have shown that disruption of β-actin gene critically impacts cell migration and mouse embryogenesis, we demonstrate here that generation of a mouse lacking β-actin protein by editing β-actin gene to encode γ-actin protein, and vice versa, does not affect cell migration and/or organism survival. Our data suggest that the essentialin vivofunction of β-actin is provided by the gene sequence independent of the encoded protein isoform. We propose that this regulation constitutes a global “silent code” mechanism that controls the functional diversity of protein isoforms.
Warning SINEs:Aluelements, evolution of the human brain, and the spectrum of neurological disease
Authors: Larsen Peter A. , Hunnicutt Kelsie E. , Larsen Roxanne J. , Yoder Anne D. , Saunders Ann M. 
Published: December 2017

AbstractAluelements are a highly successful family of primate-specific retrotransposons that have fundamentally shaped primate evolution, including the evolution of our own species.Alus play critical roles in the formation of neurological networks and the epigenetic regulation of biochemical processes throughout the central nervous system (CNS), and thus are hypothesized to have contributed to the origin of human cognition. Despite the benefits thatAlusprovide, deleteriousAluactivity is associated with a number of neurological and neurodegenerative disorders. In particular, neurological networks are potentially vulnerable to the epigenetic dysregulation ofAluelements operating across the suite of nuclear-encoded mitochondrial genes that are critical for both mitochondrial and CNS function. Here, we highlight the beneficial neurological aspects ofAluelements as well as their potential to cause disease by disrupting key cellular processes across the CNS. We identify at least 37 neurological and neurodegenerative disorders wherein deleteriousAluactivity has been implicated as a contributing factor for the manifestation of disease and, for many of these disorders, this activity is operating on genes that are essential for proper mitochondrial function. We conclude that the epigenetic dysregulation ofAluelements can ultimately disrupt mitochondrial homeostasis within the CNS. This mechanism is a plausible source for the incipient neuronal stress that is consistently observed across a spectrum of sporadic neurological and neurodegenerative disorders.List of AbbreviationsA-to-Iadenosine-to-inosineADAlzheimer’s DiseaseADARadenosine deaminase acting on RNAALSAmyotrophic Lateral SclerosisAMPAα-amino-3-hydroxy-5methyl-4-isoxazole propionateAPPamyloid precursor proteincircRNAscircular RNAsCNScentral nervous systemFLAMfree leftAlumonomerLINElong interspersed elementL1long interspersed element-1LTRlong-terminal repeatmRNAmessenger RNAPDParkinson’s Diseasepre-mRNAprecursor messenger RNASEDssuper-enhancer domainsSINEshort-interspersed elementTADstopologically associating domainsTOMMtranslocase of outer mitochondrial membrane
Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons
Authors: Eren Kemal , Weaver Steven , Ketteringham Robert , Valentyn Morné , Laird Smith Melissa , Kumar Venkatesh , Mohan Sanjay , Kosakovsky Pond Sergei L , Murrell Ben 
Published: December 2017

AbstractNext generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV-1 env, the protein of interest for HIV vaccine studies, is exceptionally challenging for long-read sequencing and analysis due to its length, high substitution rate, and extensive indel variation. While long-read sequencing is attractive in this setting, the analysis of such data is not well handled by existing methods. To address this, we introduce FLEA (Full-Length Envelope Analyzer), which performs end-to-end analysis and visualization of long-read sequencing data.FLEA consists of both a pipeline (optionally run on a high-performance cluster), and a client-side web application that provides interactive results. The pipeline transforms FASTQ reads into high-quality consensus sequences (HQCSs) and uses them to build a codon-aware multiple sequence alignment. The resulting alignment is then used to infer phylogenies, selection pressure, and evolutionary dynamics. The web application provides publication-quality plots and interactive visualizations, including an annotated viral alignment browser, time series plots of evolutionary dynamics, visualizations of gene-wide selective pressures (such as dN /dS) across time and across protein structure, and a phylogenetic tree browser.We demonstrate how FLEA may be used to process Pacific Biosciences HIV-1 env data and describe recent examples of its use. Simulations show how FLEA dramatically reduces the error rate of this sequencing platform, providing an accurate portrait of complex and variable HIV-1 env populations.A public instance of FLEA is hosted at http://flea.datamonkey.org. The Python source code for the FLEA pipeline can be found at https://github.com/veg/flea-pipeline. The client-side application is available at https://github.com/veg/flea-web-app. A live demo of the P018 results can be found at http://flea.murrell.group/view/P018.
Modeling the Structural Origins of Drug Resistance to Isoniazid via key Mutations in Mycobacterium tuberculosis Catalase-Peroxidase, KatG
Authors: Marney Matthew W. , Metzger Robert P. , Hecht David , Valafar Faramarz 
Published: December 2017

AbstractWHO reported 10.4 million new tuberculosis (TB) cases and 1.8 million deaths in 2015, making M. tuberculosis the most successful human pathogen with highest mortality among infectious diseases.[1,2] Drug-resistant TB is a major threat to global TB control.[2,3] Recently Torres et al. [4] identified 14 novel substitutions in M. tuberculosis-KatG (the enzyme associated with resistance to isoniazid—an important first-line anti-TB drug) and demonstrated that 12 of the 14 can cause INH-resistance in M. smegmatis. This study presents an in silico structure-based analysis of these 14 amino acid substitutions using homology models and x-ray crystal structures (when available) in M. tuberculosis. Our models demonstrate that several of these mutations cluster around three openings in the KatG tertiary structure which appear to initiate channels to the heme group at the catalytic center of the enzyme. We studied the effects of these mutations on the tertiary structure of KatG, focusing on conformational changes in the three channels in the protein structure. Our results suggest that the 14 novel mutations sufficiently restrict one or more of these access channels, thus potentially preventing INH from reaching the catalytic heme. These observations provide valuable insights into the structure-based origins of INH resistance and provide testable hypotheses for future experimental studies.
Positive demographic effects of nest surveillance campaigns to counter illegal harvest of the Bonelli's eagle in Sicily (Italy)
Authors: Di Vittorio M. , Rannisi G. , Di Trapani E. , Falci A. , Ciaccio A. , Rocco M. , Giacalone G. , Zafarana M. , Grenci S. , La Grua G. , Scuderi A. , Palazzolo F. , Cacopardi S. , Luiselli L. , Merlino S. , Lo Valvo M. , López‐López P. 
Published: December 2017

AbstractIllegal trade in wildlife has been identified as one of the main challenges to wildlife conservation. In 2010, an illegal trade‐ring trafficking in birds of prey was uncovered in Sicily (southern Italy). This illegal trade targeted the three most endangered species in Italy: Bonelli's eagle Aquila fasciata, Lanner falcon Falco biarmicus and Egyptian vulture Neophron percnopterus, all of them long‐lived territorial raptors threatened with extinction across their European distribution. Illegal harvest primarily involved young birds and eggs taken from nests. After the discovery of these activities, surveillance camps and camera traps connected to the mobile Global System for Mobile communications network were established in nine Bonelli's eagle breeding sites in which illegal harvest was reported. Surveillance activities resulted in a sharp reduction in illegal harvest that has contributed to the recent increase in population size and number of breeding pairs of Bonelli's eagle in the island. This population represents 95% of the entire Italian population and is catalogued as Critically Endangered in this country. Importantly, our results highlight the impact of illegal harvest on the population dynamics of endangered species as demonstrated by a population viability analysis. This is particularly important in the case of insular species for which demographic recovery due to immigration from other geographic areas is unlikely. Systematic patrols by forestry police authorities, a resolute application of Convention on International Trade in Endangered Species legislation via legal punishment, and the requirement of including all live captive specimens used for falconry in an obligatory DNA data bank would contribute to reducing the risk of extinction for small populations of endangered species of birds of prey.
Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited
Authors: Samitas K. , Carter A. , Kariyawasam H. H. , Xanthou G. 
Published: December 2017

AbstractAllergic rhinitis (AR), chronic rhinosinusitis (CRS) and asthma often co‐exist. The one airway model proposes that disease mechanisms occurring in the upper airway may mirror lower airway events. Airway remodelling is the term used to describe tissue structural changes that occur in a disease setting and reflect the dynamic process of tissue restructuring during wound repair. Remodelling has been long identified in the lower airways in asthma and is characterized by epithelial shedding, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, airway smooth muscle hyperplasia and increased angiogenesis. The concept of upper airway remodelling has only recently been introduced, and data so far are limited and often conflicting, an indication that more detailed studies are needed. Whilst remodelling changes in AR are limited, CRS phenotypes demonstrate epithelial hyperplasia, increased matrix deposition and degradation along with accumulation of plasma proteins. Despite extensive research over the past years, the precise cellular and molecular mechanisms involved in airway remodelling remain incompletely defined. This review describes our current rather limited understanding of airway remodelling processes in AR, CRS and asthma and presents mechanisms both shared and distinct between the upper and lower airways. Delineation of shared and disease‐specific pathogenic mechanisms of remodelling between the sinonasal system and the lung may guide the rational design of more effective therapeutic strategies targeting upper and lower airways concomitantly and improving the health of individuals with inflammatory airway diseases.
Identification of patterns of factors preceding severe or life‐threatening asthma exacerbations in a nationwide study
Authors: Tanaka H. , Nakatani E. , Fukutomi Y. , Sekiya K. , Kaneda H. , Iikura M. , Yoshida M. , Takahashi K. , Tomii K. , Nishikawa M. , Kaneko N. , Sugino Y. , Shinkai M. , Ueda T. , Tanikawa Y. , Shirai T. , Hirabayashi M. , Aoki T. , Kato T. , Iizuka K. , Fujii M. , Taniguchi M. 
Published: December 2017

AbstractBackgroundReducing near‐fatal asthma exacerbations is a critical problem in asthma management.ObjectivesTo determine patterns of factors preceding asthma exacerbations in a real‐world setting.MethodsIn a nationwide prospective study of 190 patients who had experienced near‐fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2‐week period before admission.ResultsThree distinct clusters of symptoms were defined employing the self‐reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle‐aged patients with low Body mass index and tendency to depression who had stopped anti‐asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle‐aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long‐acting beta‐agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild‐moderate symptoms. There were no differences in overuse of short‐acting beta‐agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters.ConclusionTo reduce severe or life‐threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti‐type 2 response‐targeted therapies should be considered for cluster C.
Drawing on Museums: Early Visual Fieldnotes by Franz Boas and the Indigenous Recuperation of the Archive
Authors: Glass Aaron 
Published: December 2017

ABSTRACTIn the first decade of his Northwest Coast fieldwork (1886–1897), Franz Boas made and commissioned a series of research drawings of Kwakwaka’wakw (Kwakiutl) objects held by museums in Berlin and elsewhere. Using them as elicitation tools, Boas added primary fieldnotes (in German, English, and Kwak'wala) directly onto them, providing a basis for his earliest publications on anthropological theory and methods as well as Kwakwaka’wakw art, song, and ceremony. Until recently, however, these visual fieldnotes—long relegated to the archive—have been severed from both the museum collections and Boas's foundational ethnographic research. In this essay, I discuss the drawings in the context of current collaborative efforts to document historic ethnographic materials with the Kwakwaka’wakw, who are recuperating such anthropological and archival resources in support of current cultural production and ceremonial revitalization. [ethnographic methods, museums, history of anthropology, Franz Boas, Kwakwaka’wakw]
Perceptions of the dental profession: a comparative analysis through scale development
Authors: Buldur Burak , Armfield Jason M. 
Published: December 2017

Dentistry is a science‐based profession that has a close interaction with people and society. However, despite this close interaction, perceptions of the dental profession by both patients and dental professionals have received little research attention. The purpose of this study was to compare the perceptions of dentists, dental students, and patients toward the dental profession through the development and testing of the Dental Profession Perceptions Scale (DPPS). The DPPS contains a total of 17 items measured on a 5‐point Likert response scale. The DPPS showed excellent internal reliability (Cronbach's α = 0.92) and test–retest reliability (r = 0.93). Explanatory and confirmatory factor analyses of the DPPS showed that dentists’, dental students’, and patients’ perceptions of the dental profession could be grouped according to ‘status’, ‘human’, and ‘scientific’ factors. There were no statistically significant differences between participants’ DPPS total or sub‐scale scores according to dental group, gender, or income. The DPPS developed can be used in future studies as a psychometrically sound measuring tool. Further studies should examine the factors that may affect the perceptions of the dental profession in different societies and cultures.
Small‐animal PET imaging analysis with [18F]FHBG in a mouse model of HSV1‐tk gene expression in melanoma
Authors: Lee Onseok , Kim Jaeyoung , Oh Chilhwan 
Published: December 2017

AbstractThe purpose of this study was to establish a small‐animal model for molecular imaging and to acquire basic data on assessing the efficacy of candidate melanoma drugs using small‐animal PET imaging analysis with [18F]FHBG for herpes simplex virus 1‐thymidine kinase (HSV1‐tk) gene expression in a melanoma mouse model. The B16 melanoma cell line was transduced with a recombinant lentiviral vector containing the HSV1‐tk gene and inoculated into the back skin of C57BL/6J mice. [18F]FHBG PET imaging showed better contrast for HSV1‐tk(+) melanomas compared to brain, heart, gall bladder, intestine and kidney than did [18F]FDG PET imaging.
Assessment of Nanosecond Laser Ablation Multi‐Collector Inductively Coupled Plasma‐Mass Spectrometry for Pb and Sr Isotopic Determination in Archaeological Glass: Mass Bias Correction Strategies and Results for Corning Glass Reference Materials
Authors: Van Ham‐Meert Alicia , Chernonozhkin Stepan M. , Van Malderen Stijn J.M. , Van Acker Thibaut , Vanhaecke Frank , Degryse Patrick 
Published: December 2017

This work presents an evaluation of various methods for in situ high‐precision Sr and Pb isotopic determination in archaeological glass (containing 100–500 μg g−1 target element) by nanosecond laser ablation multi‐collector‐inductively coupled plasma‐mass spectrometry (ns‐LA‐MC‐ICP‐MS). A set of four soda‐lime silicate glasses, Corning A–D, mimicking the composition of archaeological glass and produced by the Corning Museum of Glass (Corning, New York, USA), were investigated as candidates for matrix‐matched reference materials for use in the analysis of archaeological glass. Common geological reference materials with known isotopic compositions (USGS basalt glasses BHVO‐2G, GSE‐1G and NKT‐1G, soda‐lime silicate glass NIST SRM 610 and several archaeological glass samples with known Sr isotopic composition) were used to evaluate the ns‐LA‐MC‐ICP‐MS analytical procedures. When available, ns‐LA‐MC‐ICP‐MS results for the Corning glasses are reported. These were found to be in good agreement with results obtained via pneumatic nebulisation (pn) MC‐ICP‐MS after digestion of the glass matrix and target element isolation. The presence of potential spectral interference from doubly charged rare earth element (REE) ions affecting Sr isotopic determination was investigated by admixing Er and Yb aerosols by means of pneumatic nebulisation into the gas flow from the laser ablation system. It was shown that doubly charged REE ions affect the Sr isotope ratios, but that this could be circumvented by operating the instrument at higher mass resolution. Multiple strategies to correct for instrumental mass discrimination in ns‐LA‐MC‐ICP‐MS and the effects of relevant interferences were evaluated. Application of common glass reference materials with basaltic matrices for correction of ns‐LA‐MC‐ICP‐MS isotope data of archaeological glasses results in inaccurate Pb isotope ratios, rendering application of matrix‐matched reference materials indispensable. Correction for instrumental mass discrimination using the exponential law, with the application of Tl as an internal isotopic standard element introduced by pneumatic nebulisation and Corning D as bracketing isotopic calibrator, provided the most accurate results for Pb isotope ratio measurements in archaeological glass. Mass bias correction relying on the power law, combined with intra‐element internal correction, assuming a constant 88Sr/86Sr ratio, yielded the most accurate results for 87Sr/86Sr determination in archaeological glasses
Syndrome of Transient Headache and Neurologic Deficits With Cerebrospinal Fluid Lymphocitosis Should Be Considered in Children Presenting With Acute Confusional State
Authors: Moavero Romina , Papetti Laura , Tarantino Samuela , Battan Barbara , Salfa Irene , Deodati Annalisa , Schiaffini Riccardo , Vigevano Federico , Valeriani Massimiliano 
Published: December 2017

BackgroundTransient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is benign and self‐limited, with neurologic deficits including sensory disturbance of one body side, aphasia, nausea/vomiting, weakness, decreased vision, homonymous hemianopsia, photophobia. Acute confusional state can rarely occur. Papilledema and intracranial hypertension have also been described. It is a rare entity mainly affecting adults; however, it has been sporadically described in children and adolescents.Main findingsIn this clinical observational study, we describe a clinical series of three consecutive pediatric patients being diagnosed with HaNDL after presenting with altered consciousness, papilledema, and increased intracranial pressure. They all recovered without relapses.ConclusionPresentation during childhood and adolescence is rare; the majority of pediatric cases presented with altered consciousness, which is infrequent in HaNDL. This may suggest that in childhood this symptom might be more common than in adults. All three patients presented with increased intracranial pressure and papilledema, thus suggesting that these aspects should be investigated in all patients presenting with this clinical pattern. Finally, all our patients began to suffer from migraine. This feature, together with the benign course of the disease, could favor the hypothesis of a migrainous pathophysiology of this syndrome, although this remains a speculative.