bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans
Authors: Schüler Christina , Fischer Elisabeth , Shaltiel Lior , Steuer Costa Wagner , Gottschalk Alexander 
Published: September 2015

AbstractCardiac arrhythmias are often associated with mutations in ion channels or other proteins. To enable drug development for distinct arrhythmias, model systems are required that allow implementing patient-specific mutations. We assessed a muscular pump inCaenorhabditis elegans. The pharynx utilizes homologues of most of the ion channels, pumps and transporters defining human cardiac physiology. To yield precise rhythmicity, we optically paced the pharynx using channelrhodopsin-2. We assessed pharynx pumping by extracellular recordings (electropharyngeograms—EPGs) and by a novel video-microscopy based method we developed, which allows analyzing multiple animals simultaneously. Mutations in the L-type VGCC (voltage-gated Ca2+-channel) EGL-19 caused prolonged pump duration, as found for analogous mutations in the Cav1.2 channel, associated with long QT syndrome.egl-19mutations affected ability to pump at high frequency and induced arrhythmicity. The pharyngeal neurons did not influence these effects. We tested whether drugs could ameliorate arrhythmia in the optogenetically paced pharynx. The dihydropyridine analog Nemadipine A prolonged pump duration in wild type and reduced or prolonged pump duration of distinctegl-19alleles, thus indicating allele-specific effects. In sum, our model may allow screening of drug candidates affecting specific VGCCs mutations and permit to better understand the effects of distinct mutations on a macroscopic level.
Raster image cross-correlation analysis for spatiotemporal visualization of intracellular degradation activities against exogenous DNAs
Authors: Sasaki Akira , Yamamoto Johtaro , Jin Takashi , Kinjo Masataka 
Published: September 2015

AbstractReducing intracellular DNA degradation is critical to enhance the efficiency of gene therapy. Exogenous DNA incorporation into cells is strictly blocked by the defense machinery of intracellular nuclease activity. Raster image correlation spectroscopy (RICS) and raster image cross-correlation spectroscopy (cross-correlation RICS; ccRICS) are image-based correlation methods. These powerful tools allow the study of spatiotemporal molecular dynamics. Here we performed spatiotemporal ccRICS analyses of fluorescent DNA and directly monitored the process of exogenous DNA degradation in living cell cytoplasm. Such direct monitors of DNA degradation allow us to determine the fate of the exogenous DNA in living cells. On comparing the process in living cells, our study shows that cytoplasmic nuclease activity differs between cell lines; therefore, we propose that the difference of nuclease activity in cytoplasm dictates a different resistance to exogenous DNA incorporation. New insight on efficient gene delivery can be provided with our study.
Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs
Authors: Qian Lili , Tang Maoxue , Yang Jinzeng , Wang Qingqing , Cai Chunbo , Jiang Shengwang , Li Hegang , Jiang Ke , Gao Pengfei , Ma Dezun , Chen Yaoxing , An Xiaorong , Li Kui , Cui Wentao 
Published: September 2015

AbstractMyostatin (MSTN) is a dominant inhibitor of skeletal muscle development and growth. Mutations in MSTN gene can lead to muscle hypertrophy or double-muscled (DM) phenotype in cattle, sheep, dog and human. However, there has not been reported significant muscle phenotypes in pigs in association with MSTN mutations. Pigs are an important source of meat production, as well as serve as a preferred animal model for the studies of human disease. To study the impacts of MSTN mutations on skeletal muscle growth in pigs, we generated MSTN-mutant Meishan pigs with no marker gene via zinc finger nucleases (ZFN) technology. The MSTN-mutant pigs developed and grew normally, had increased muscle mass with decreased fat accumulation compared with wild type pigs and homozygote MSTN mutant (MSTN−/−) pigs had apparent DM phenotype and individual muscle mass increased by 100% over their wild-type controls (MSTN+/+) at eight months of age as a result of myofiber hyperplasia. Interestingly, 20% MSTN-mutant pigs had one extra thoracic vertebra. The MSTN-mutant pigs will not only offer a way of fast genetic improvement of lean meat for local fat-type indigenous pig breeds, but also serve as an important large animal model for biomedical studies of musculoskeletal formation, development and diseases.
Griffiths phases and localization in hierarchical modular networks
Authors: Ódor Géza , Dickman Ronald , Ódor Gergely 
Published: September 2015

AbstractWe study variants of hierarchical modular network models suggested by Kaiser and Hilgetag [ Front. in Neuroinform.,4 (2010) 8] to model functional brain connectivity, using extensive simulations and quenched mean-field theory (QMF), focusing on structures with a connection probability that decays exponentially with the level index. Such networks can be embedded in two-dimensional Euclidean space. We explore the dynamic behavior of the contact process (CP) and threshold models on networks of this kind, including hierarchical trees. While in the small-world networks originally proposed to model brain connectivity, the topological heterogeneities are not strong enough to induce deviations from mean-field behavior, we show that a Griffiths phase can emerge under reduced connection probabilities, approaching the percolation threshold. In this case the topological dimension of the networks is finite and extended regions of bursty, power-law dynamics are observed. Localization in the steady state is also shown via QMF. We investigate the effects of link asymmetry and coupling disorder and show that localization can occur even in small-world networks with high connectivity in case of link disorder.
How musical expertise shapes speech perception: evidence from auditory classification images
Authors: Varnet Léo , Wang Tianyun , Peter Chloe , Meunier Fanny , Hoen Michel 
Published: September 2015

AbstractIt is now well established that extensive musical training percolates to higher levels of cognition, such as speech processing. However, the lack of a precise technique to investigate the specific listening strategy involved in speech comprehension has made it difficult to determine how musicians’ higher performance in non-speech tasks contributes to their enhanced speech comprehension. The recently developed Auditory Classification Image approach reveals the precise time-frequency regions used by participants when performing phonemic categorizations in noise. Here we used this technique on 19 non-musicians and 19 professional musicians. We found that both groups used very similar listening strategies, but the musicians relied more heavily on the two main acoustic cues, at the first formant onset and at the onsets of the second and third formants onsets. Additionally, they responded more consistently to stimuli. These observations provide a direct visualization of auditory plasticity resulting from extensive musical training and shed light on the level of functional transfer between auditory processing and speech perception.
Fluorescent light energy harvesting using a capacitive touch screen
Authors: Kim Seulkirom , Kim Katherine A. , Bien Franklin 
Published: September 2015

This Letter presents a fluorescent light energy harvesting method using a capacitive touch screen to charge a phone battery. The proposed idea utilises additional power circuitry, i.e., AC to DC and DC to DC converters to provide DC power to the load. Fluorescent light used in the experiment had a 29.56‐V peak‐to‐peak voltage at 38 kHz frequency. Experimental measurements show that the fluorescent light energy harvesting system can generate 835 μW of power.
Arbeitsbedingter Stress und der Allostatic Load Index – eine systematische Übersichtsarbeit
Authors: Mauss D. , Li J. , Schmidt B. , Angerer P. , Jarczok M. 
Published: September 2015

Zusammenfassung
Ziel: Arbeitsbedingter Stress ist eine zunehmende gesellschaftliche Herausforderung und wird in ursächlichen Zusammenhang mit reduzierter Gesundheit, weniger Wohlbefinden und niedrigerer Produktivität von Mitarbeitern gebracht. Der Allostatic Load Index (ALI) ist ein Messkatalog für akkumulierte physiologische Stressfolgen. Die vorliegende Übersichtarbeit beschreibt das bisherige Wissen über den Zusammenhang von arbeitsbedingten Stress und ALI bei erwachsenen Beschäftigten.
Methodik: Eine systematische Literaturrecherche auf Basis des PRISMA Statements wurde in 21 Datenbanken inklusive Medline, PubPsych, MedPilot und Cochrane Register durchgeführt. Es wurden ausschließlich Originalarbeiten berücksichtigt, die arbeitsbedingten Stress und medizinische Parameter mithilfe des ALI untersuchten. Angaben zur Studienpopulation, analytische Methoden und Ergebnisse wurden erfasst. Die methodologische Qualität wurde durch eine standardisierte Checkliste geprüft.
Ergebnisse: Es wurden 9 Artikel zu Querschnittstudien im Zeitraum 2003–2013 identifiziert, die Daten von insgesamt 3 532 Mitarbeitern aus 5 Ländern beinhalteten. Sieben Studien berichteten einen positiven und signifikanten Zusammenhang von arbeitsbedingtem Stress und ALI, während 2 Studien keinen oder einen nicht signifikanten Zusammenhang fanden. Es wurde substantielle Heterogenität bezüglich der angewendeten Methoden sowie der Studienqualität festgestellt.
Schlussfolgerung: Diese Übersichtarbeit zeigt einen positiven Zusammenhang von Arbeitsstress und ALI in Querschnittstudien. Weitere Untersuchungen in der arbeitenden Bevölkerung sollten diesen Zusammenhang im Längsschnitt nachweisen.
Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility
Authors: Price Paul A. , Tanner Houston R. , Dillon Brett A. , Shabab Mohammed , Walker Graham C. , Griffitts Joel S. 
Published: September 2015

Significance
The agriculturally important symbiosis between nitrogen-fixing bacteria (rhizobia) and their legume hosts occurs within root nodules. This partnership requires a molecular dialogue that ensures specificity and directs the codevelopment of the two organisms during nodule formation. This paper characterizes a protein, host range restriction peptidase (HrrP), which plays a role in this dialogue. Rhizobial strains that express HrrP tend to exhibit more parasitic properties, such as failing to provide fixed nitrogen for their hosts and proliferating more abundantly within nodule tissue. HrrP likely exhibits these properties by actively degrading plant-derived chemical signals that normally stimulate symbiotic cooperation.
Nucleosome competition reveals processive acetylation by the SAGA HAT module
Authors: Ringel Alison E. , Cieniewicz Anne M. , Taverna Sean D. , Wolberger Cynthia 
Published: September 2015

Significance
Crosstalk between histone modifications regulates transcription by establishing spatial and temporal relationships between histone marks. Despite discoveries of reader domains that physically associate with chromatin-modifying enzymes, the mechanisms by which recognition of one modification triggers other kinds of modifications have remained elusive. Gcn5 is the catalytic subunit of the Spt-Ada-Gcn5 acetyltransferase (SAGA) histone acetyltransferase (HAT) module, which also recognizes histone 3 lysine 4 trimethylation (H3K4me3) through the tandem Tudor domain-containing protein Sgf29. Although previous studies could not connect H3K4me3 recognition to differences in acetylation by Gcn5, we report enhanced processivity by the HAT module on methylated substrates using a previously unpublished histone color-coding assay. Our work defines a mechanism for histone crosstalk that may account for genome-wide patterns of Gcn5-mediated acetylation.
Low load for disruptive mutations in autism genes and their biased transmission
Authors: Iossifov Ivan , Levy Dan , Allen Jeremy , Ye Kenny , Ronemus Michael , Lee Yoon-ha , Yamrom Boris , Wigler Michael 
Published: September 2015

Significance
Gene targets of de novo mutation in autistic children have a lighter load of rare disruptive variation than typical human genes. This finding suggests such mutations are under negative selection and autism genes are highly vulnerable to mutation. Disruptive variants in these genes have biased transmission: They are more frequently transmitted to affected children, and more often from mothers than from fathers. Targets of mutation in lower intelligence quotient (IQ) affected children have a lower load of disruptive mutations than targets of mutation in higher IQ affected children. Biased transmission is seen more frequently to affected children of lower IQ. These observations are consistent with a correlation between severity of mutations and phenotype, and based on them, we list candidate autism genes ordered by likelihood.
Physical fitness normative values for 6–18‐year‐old Greek boys and girls, using the empirical distribution and the lambda, mu, and sigma statistical method
Authors: Tambalis Konstantinos D. , Panagiotakos Demosthenes B. , Psarra Glykeria , Daskalakis Stelios , Kavouras Stavros A. , Geladas Nickos , Tokmakidis Savas , Sidossis Labros S. 
Published: September 2015

AbstractThe aim of the this study was to establish age‐ and gender‐specific physical fitness normative values and to compare percentiles and Z scores values in a large, nationwide sample of Greek children aged 6–18 years. From March 2014 to May 2014, a total of 424,328 boys and girls aged 6–18 years who attended school in Greece were enrolled. The studied sample was representative, in terms of age–sex distribution and geographical region. Physical fitness tests (i.e. 20 m shuttle run test (SRT), standing long jump, sit and reach, sit‐ups, and 10 × 5 m SRT) were performed and used to calculate normative values, using the percentiles of the empirical distributions and the lambda, mu, and sigma statistical method. Normative values were presented as tabulated percentiles for five health‐related fitness tests based on a large data set comprising 424,328 test performances. Boys typically scored higher than girls on cardiovascular endurance, muscular strength, muscular endurance, and speed/agility, but lower on flexibility (all p values <0.001). Older boys and girls had better performances than younger ones (p < 0.001). Physical fitness tests' performances tended to peak at around the age of 15 years in both sexes. The presented population‐based data are the most up‐to‐date sex‐ and age‐values for the health‐related fitness of children and adolescents in Greece and can be used as standard values for fitness screening and surveillance systems and for comparisons among the same health‐related fitness scores of children from other countries similar to Greece. Schools need to make efforts to improve the fitness level of the schoolchildren through the physical education curriculum to prevent cardiovascular risk.
Shakespeare and Stratford-upon-Avon
Authors: Wells Stanley 
Published: September 2015

Abstract
William Shakespeare is thought to have been born on 23 April 1564 and died on 23 April 1616. ‘Shakespeare and Stratford-upon-Avon’ describes his life in the Warwickshire market town with his parents, John Shakespeare and Mary Arden, and his siblings. Shakespeare’s works confirm he had a good education, most likely at the grammar school. He married Anne Hathaway in 1582 and they had three children. He moved to London, the centre of the literary and theatre world, some time after his children were born, but his family remained in Stratford and Shakespeare retained strong links with the town to the end of his life.
Theatre in Shakespeare’s time
Authors: Wells Stanley 
Published: September 2015

Abstract
Both drama and theatre were developing rapidly in Shakespeare’s early years. ‘Theatre in Shakespeare’s time’ explains how Shakespeare followed in the footsteps of the first great wave of stage writers known as the University Wits—John Lyly, Thomas Lodge, Christopher Marlowe, George Peele, Thomas Nashe, and Robert Greene—learning from them and collaborating with them. It describes the London theatrical scene, the playing spaces, and the actors of the time before outlining Shakespeare’s early career, the narrative poems that kept him afloat financially, and introducing the Lord Chamberlain’s, and later King’s Men, the acting company that formed in 1594.
Shakespeare and comic form
Authors: Wells Stanley 
Published: September 2015

Abstract
Nearly half of Shakespeare’s plays, extending throughout his career, are written in comic form though they play a wide range of variations on it. ‘Shakespeare and comic form’ describes the five earliest as the lightest in tone, but in the five that follow, Shakespeare introduces an antagonist who must be expelled before the play can end happily. The later comedies were written for the Lord Chamberlain’s Men. The plays considered are The Two Gentlemen of Verona, The Taming of the Shrew, The Comedy of Errors, Love’s Labour’s Lost, A Midsummer Night’s Dream, The Merchant of Venice, The Merry Wives of Windsor, Much Ado About Nothing, As You Like It, and Twelfth Night.
Return to tragedy
Authors: Wells Stanley 
Published: September 2015

Abstract
‘Return to tragedy’ begins by looking at the plays Hamlet, Othello, King Lear, and Macbeth. It is a tribute to the Globe playgoers that Shakespeare’s longest play—Hamlet—one of the most complex and intellectually ambitious ever written, was also one of his most popular. When the Lord Chamberlain’s Men became the King’s Men in 1603, Shakespeare’s comedies, and his work in general, took on darker tones and a new seriousness. Both Measure for Measure and All’s Well That Ends Well place their heroines in far more painful situations than those in which the central characters of the earlier comedies find themselves.
PathwaysWeb: a gene pathways API with directional interactions, expanded gene ontology, and versioning
Authors: Melott James M. , Weinstein John N. , Broom Bradley M. 
Published: September 2015

Abstract
Summary: PathwaysWeb is a resource-based, well-documented web system that provides publicly available information on genes, biological pathways, Gene Ontology (GO) terms, gene–gene interaction networks (importantly, with the directionality of interactions) and links to key-related PubMed documents. The PathwaysWeb API simplifies the construction of applications that need to retrieve and interrelate information across multiple, pathway-related data types from a variety of original data sources. PathwaysBrowser is a companion website that enables users to explore the same integrated pathway data. The PathwaysWeb system facilitates reproducible analyses by providing access to all versions of the integrated datasets. Although its GO subsystem includes data for mouse, PathwaysWeb currently focuses on human data. However, pathways for mouse and many other species can be inferred with a high success rate from human pathways.
Availability and implementation: PathwaysWeb can be accessed via the Internet at http://bioinformatics.mdanderson.org/main/PathwaysWeb:Overview.
Contact: jmmelott@mdanderson.org
Supplementary information: Supplementary data are available at Bioinformatics online.
OP‐4 ADVANCES IN TISSUE ENGINEERING TO REGENERATE THE INTESTINAL EPITHELIUM
Authors: Meran L , Li V , De Coppi P 
Published: September 2015

Introduction:Irreversible intestinal failure (IF) due to anatomical or functional loss is a devastating condition is associated with significant morbidity and mortality. Patients referred for intestinal transplantation suffer low survival rates due to the high graft‐rejection rate and sepsis as a consequence long‐term immunosuppression. These clinical challenges reveal an urgent need for research into new treatments for IF. Here, we present recent advances in our work on intestinal tissue engineering.Methods:Ethical approval is in place to collect intestinal tissue from patients at Great Ormond Street Hospital. Intestinal crypts were isolated and organoids were cultured as previously described. Decellularization of whole intestinal sections was performed using 2 cycles of the Detergent Enzymatic Treatment (DET) as previously reported. Organoids were cultured on the epithelial surface of the acellular matrix in vitro for 10 days. Cell survival was analysed by histology, immunofluorescence, immunohistochemistry and electron microscopy techniques.Results:Intestinal crypts from the small intestine and colon were successfully isolated from endoscopic biopsies and cultured in order to generate 3 dimensional organoids. The presence of goblet cells and enterocyte cells were confirmed on immunohistochemistry. Whole sections of intestine of varying lengths were successfully decellularized and assessed using H&E staining and scanning electron microscopy. Organoids were seeded onto the epithelial surface of the acellular intestinal matrices and allowed to engraft for a period of 10 days in vitro. The formation of a neo‐epithelium with evidence of a microvillus brush border was evident after 10 days in culture. Furthermore, the cells had successfully migrated into the crypt domains of the matrix.Conclusions:We demonstrate the potential of tissue engineering for intestinal failure by combining organoid cultures with decellularization expertise. Our results confirm human intestinal organoids to be the ideal source of progenitor cells to regenerate the intestinal epithelium, with potential clinical applications for transplantation.
OP‐9 MODULATION OF THE RECTOANAL INHIBITORY REFLEX IN PATIENTS WITH MYELOMENINGOCELE WITH AND WITHOUT BLADDER AUGMENTATION
Authors: Kardosh Fernanda Pilate , de Morais Mauro Batista , Miasato Marcio , Junior Antonio Macedo , Tahan Soraia 
Published: September 2015

Introduction:Some patients with myelomeningocele need bladder augmentation (augmentation cystoplasty). The aim of this study was to evaluate the relationship between the bladder augmentation and the rectoanal inhibitory reflex (RAIR) modulation in patients with myelomeningocele. The modulation of the anorectal inhibitory reflex in accord the use of oxybutynin chloride was also evaluated.Methods:It is a cross‐sectional and comparative study. We studied a convenience sample consisting of 24 children and adolescents with myelomeningocele aged between 4 and 18 years. Ten of these 24 patients had surgery to expand the bladder. Anorectal manometry of perfusion were performed with 8‐channel radial catheter (Dynamed®) in latex free protocol. The evaluation of the (RAIR) modulation was determined by inflating the balloon with 20 mL of air in rectal. The RAIR modulation was determined by duration (seconds) and amplitude (% relaxation) of RAIR.Results:RAIR was present in all the patients. The duration of the RAIR (seconds) with 20 mL and 40 mL was similar in the both groups, with or without bladder augmentation (27.11 ± 11.95; 27.37 ± 9.29; p = 0.953 and 30.32 ± 7.30; 32.08 ± 10.13, p = 0.653). The RAIR amplitude with 20 mL and 40 mL was higher in the patients with bladder augmentation than in patients without bladder augmentation (63.87 ± 24.58; 82.31 ± 15.94, p = 0.036 and 68.06 ± 14.80;88.93 ± 16.31, p = 0.004). The patients who used oxybutynin chloride presented higher amplitude (% relaxation) in relation those did not used this drug, with 20 mL (80.91 ± 15.37 and 65.21 ± 25.73; p = 0.074) and 40 mL (85.78 ± 15.96 and 73.05 ± 19.29; p = 0.084), however, the statistic evaluation did not reach significance.Conclusions:The RAIR modulation is different between patients with and without bladder augmentation. The use of oxybutynin chloride also appears to interfere in the RAIR, increasing its amplitude.